Ethnic disparities in the risk of colorectal adenomas associated with lipid levels: a retrospective multiethnic study.

PubMed

Davis-Yadley, Ashley H; Lipka, Seth; Shen, Huafeng; Devanney, Valerie; Swarup, Supreeya; Barnowsky, Alex; Silpe, Jeff; Mosdale, Josh; Pan, Qinshi; Fridlyand, Svetlana; Sreeharshan, Suhas; Abraham, Albin; Viswanathan, Prakash; Krishnamachari, Bhuma

2015-03-01

Although data exists showing that uncontrolled lipid levels in white and black patients is associated with colorectal adenomas, there are currently no studies looking only at the Hispanic population. With the rapid increase in the Hispanic population, we aimed to look at their risk of colorectal adenomas in association with lipid levels. We retrospectively analyzed 1473 patients undergoing colonoscopy from 2009 to 2011 at a community hospital. Statistical analysis was performed using Chi-squared for categorical variables and t test for continuous variables with age-, gender-, and race-adjusted odds ratios. Unconditional logistic regression model was used to estimate 95 % confidence intervals (CI). SAS 9.3 software was used to perform all statistical analysis. In our general population, there was an association with elevated triglyceride levels greater than 150 and presence of multiple colorectal adenomas with odds ratio (OR) 1.60 (1.03, 2.48). There was an association with proximal colon adenomas and cholesterol levels between 200 and 239 with OR 1.57 (1.07, 2.30), and low-density lipoprotein (LDL) levels of greater than 130 with OR 1.54 (1.04, 2.30). There was no association between high-density lipoproteins (HDL) levels and colorectal adenomas. The Hispanic population showed no statistical correlation between elevated triglycerides, cholesterol, or LDL with the presence, size, location, or multiplicity of colorectal adenomas. We found a significant correlation between elevated lipid levels and colorectal adenomas in white and black patients; however, there was no such association in the Hispanic population. This finding can possibly be due to environmental factors such as dietary, colonic flora, or genetic susceptibility, which fosters further investigation and research.

Receptor mediated elevation in FABP4 levels by advanced glycation end products induces cholesterol and triacylglycerol accumulation in THP-1 macrophages.

PubMed

Wang, Xiao Qun; Yang, Ke; He, Yu Song; Lu, Lin; Shen, Wei Feng

2011-06-01

Excessive formation of advanced glycation end products (AGE) and lipid accumulation in macrophages play a pivotal role in the progression of atherosclerosis in diabetes mellitus. This study aimed to determine the molecular link between AGE-induced fatty acid binding protein 4 (FABP4) expression and macrophage lipid accumulation. AGE-BSA markedly increased macrophage FABP4 expression via engagement of RAGE, a 35-kDa transmembrane receptor that is able to bind extracellular AGE and responsible for the corresponding signal transduction, whereas knockdown of RAGE significantly reversed the FABP4 up-regulation. This effect was further paralleled with elevated intracellular total cholesterol and triacylglycerol levels. Finally, administration of FABP4 inhibitor totally abolished the increased lipid contents in response to AGE-BSA. These results indicate that FABP4 up-regulation is responsible for the enhanced macrophage lipid accumulation by AGE, which may underlie the accelerated formation of foam cells and development of atherosclerotic cardiovascular diseases in diabetic patients.

Antimicrobial Lipids: Novel Innate Defense Molecules are Elevated in Sinus Secretions of Patients with Chronic Rhinosinusitis

PubMed Central

Lee, Jivianne T.; Jansen, Mike; Yilma, Abebayehu N.; Nguyen, Angels; Desharnais, Robert; Porter, Edith

2010-01-01

Introduction Airway secretions possess intrinsic antimicrobial properties that contribute to the innate host defense of the respiratory tract. These microbicidal capabilities have largely been attributed to the presence of antibacterial polypeptides. However, recent investigation has demonstrated that host-derived lipids including cholesteryl esters also exhibit antimicrobial properties. The purpose of this study was to determine whether sinus secretions contain such antimicrobial lipids and to compare the lipid composition in patients with and without chronic rhinosinusitis (CRS). Methods Maxillary sinus fluid was obtained via antral lavage from subjects with (7) and without (9) a history of CRS. Following specimen collection, total lipid was extracted according to Bligh & Dyer and lipid profiles were obtained by reverse phase HPLC on an amide-embedded C18 column. In addition, the neutrophil specific antimicrobial peptides HNP1-3 were quantified by immunoblotting. Results Lipids were identified in the maxillary sinus secretions of patients with and without CRS including cholesteryl esters. However, levels of lipid composition differed between the two groups with CRS patients exhibiting greater amounts of all classes of lipids; reaching over 10-fold higher concentration when compared to nonCRS patients. This increase was independent of HNP1-3 content. Conclusions Sinus secretions of patients with CRS appear to demonstrate elevated levels of antimicrobial lipids compared to controls independent from neutrophil influx. This upregulation suggests that host-derived lipids act as mediators of mucosal immunity in CRS. Further study is necessary to determine if such antimicrobial lipids function alone or synergistically with antibacterial peptides in conferring such inherent microbicidal properties. PMID:20338107

Vitamin D3-induced hypercalcemia increases carbon tetrachloride-induced hepatotoxicity through elevated oxidative stress in mice

PubMed Central

Usuda, Haruki; Miura, Nobuhiko; Fukuishi, Nobuyuki; Nonogaki, Tsunemasa; Onosaka, Satomi

2017-01-01

The aim of this study was to determine whether calcium potentiates acute carbon tetrachloride (CCl4) -induced toxicity. Elevated calcium levels were induced in mice by pre-treatment with cholecalciferol (vitamin D3; V.D3), a compound that has previously been shown to induce hypercalcemia in human and animal models. As seen previously, mice injected with CCl4 exhibited increased plasma levels of alanine aminotransferase, aspartate aminotransferase, and creatinine; transient body weight loss; and increased lipid peroxidation along with decreased total antioxidant power, glutathione, ATP, and NADPH. Pre-treatment of these animals with V.D3 caused further elevation of the values of these liver functional markers without altering kidney functional markers; continued weight loss; a lower lethal threshold dose of CCl4; and enhanced effects on lipid peroxidation and total antioxidant power. In contrast, exposure to V.D3 alone had no effect on plasma markers of liver or kidney damage or on total antioxidant power or lipid peroxidation. The potentiating effect of V.D3 was positively correlated with elevation of hepatic calcium levels. Furthermore, direct injection of CaCl2 also enhanced CCl4-induced hepatic injury. Since CaCl2 induced hypercalcemia transiently (within 3 h of injection), our results suggest that calcium enhances the CCl4-induced hepatotoxicity at an early stage via potentiation of oxidative stress. PMID:28448545

[Effects of APOC3 polymorphisms on the plasma lipids in healthy adolescents with different body mass index].

PubMed

Song, Yong-yan; Gong, Ren-rong; Zhang, Zhen; Li, Yuan-hao; Fan, Mei; Hu, Min-shan; Fang, Ding-zhi

2015-01-01

To investigate the possible effects of apolipoprotein C I gene (APOC3) polymorphisms on plasma lipids in healthy adolescents with different body mass index (BMI). Seven hundred and twenty three adolescents were divided into four groups according to BMI: group 1 CBMI= (17.80 +/- 0.75) kg/m2,n=180], group 2 [BMI = (19.39 +/- 0.32) kg/m2, n=182), group 3 [BMI= (20.68 +/- 0.43) kg/m2, n=1813 and group 4 [BMI= (23.40 +/- 2.05) kg/m2 ,n=180J. Fasting venous blood samples were collected, plasma lipids were determined and genome DNA was extracted for determining the genotypes of the APOC3 Sst I and -482C>T polymorphisms by PCR-RFLP. With the elevation of BMI, height and plasma high-density lipoprotein cholesterol decreased significantly (P<0.001 for both), body mass, waist circumference, hip circumference, waist/hip ratio, plasma triglycerides (TG), total cholesterol and low-density lipoprotein cholesterol levels increased significantly (P<0.001 for all). No significant differences in TG levels among Sst I genotypes were observed in group 1, group 2 and group 3; but in group 4, significant differences in TG levels among Sst I genotypes were observed, S2 carriers had higher TG levels than the adolescents with S1S1 genotype. No significant differences in plasma lipids among -482C>T genotypes were observed in all groups. The elevation of plasma TG levels by the S2 allele of APOC3 Sst I polymorphism is associated with BMI. It is possible that the reduction of body mass could favorably modulate the elevation of TG levels by S2 allele in healthy adolescents.

Impact of lipid disorders on mortality among Saudi patients with heart failure

PubMed Central

Al Qahtani, M.; Al Backer, T.; Al Anazi, T.; Al Johani, N.; Binsalih, S.; AlGobain, M.; Alshammari, H.

2014-01-01

Background Dyslipidemia, a known cardiovascular risk factor, is extremely common among Saudis, both adults and children. The impact, however, of dyslipidemia and several other lipid disorders in patients with congestive heart failure in this particular population has not been documented. This study aims to fill the gap. Methods This retrospective, single center study was conducted at King Abdulaziz Medical City, Riyadh, Saudi Arabia. Of the 500 cases seen during the period between 2002 and 2008, 392 were included in the study. Charts were reviewed and information on medical history, medications, and lipid status were documented. Results Low HDL-cholesterol level was the most common lipid disorder with 82.9%, followed by hypertriglyceridemia (35.2%), atherogenic dyslipidemia (27.8%), and hypercholesterolemia (9.2%). Diabetes mellitus was the single most significant predictor of mortality (p = 0.001). Among the lipid disorders, only low levels of HDL-cholesterol contributed to significant mortality risk [OR 1.29 (Confidence Interval 1.04–1.59) (p-value < 0.01)] adjusted for age, gender and statin use. Conclusion The results of this study suggest that emphasis should be on the elevation of HDL-cholesterol levels among subjects with congestive heart failure, without compromising any ongoing management of LDL-lowering drugs. Management should not be limited to conventional statin use and should promote other treatments to elevate HDL-cholesterol levels. PMID:25870502

Antimicrobial lipids: novel innate defense molecules are elevated in sinus secretions of patients with chronic rhinosinusitis.

PubMed

Lee, Jivianne T; Jansen, Mike; Yilma, Abebayehu N; Nguyen, Angels; Desharnais, Robert; Porter, Edith

2010-01-01

Airway secretions possess intrinsic antimicrobial properties that contribute to the innate host defense of the respiratory tract. These microbicidal capabilities have largely been attributed to the presence of antibacterial polypeptides. However, recent investigation has indicated that host-derived lipids including cholesteryl esters also exhibit antimicrobial properties. The purpose of this study was to determine whether sinus secretions contain such antimicrobial lipids and to compare the lipid composition in patients with and without chronic rhinosinusitis (CRS). Maxillary sinus fluid was obtained via antral lavage from subjects with (seven patients) and without (nine patients) a history of CRS. After specimen collection, total lipid was extracted according to Bligh and Dyer (Bligh EG and Dyer WJ, A rapid method of total lipid extraction and purification, Can J Biochem Physiol 37:911-918, 1959) and lipid profiles were obtained by reverse phase high-performance liquid chromatography on an amide-embedded C18 column. In addition, the neutrophil-specific antimicrobial peptides human neutrophil peptides 1-3 (HNP1-3) were quantified by Western immunoblotting. Lipids, including cholesteryl esters, were identified in the maxillary sinus secretions of patients with and without CRS. However, levels of lipid composition differed between the two groups with CRS patients exhibiting greater amounts of all classes of lipids, reaching over 10-fold higher concentration when compared with non-CRS patients. This increase was independent of HNP1-3 content. Sinus secretions of patients with CRS appear to show elevated levels of antimicrobial lipids compared with controls independent from neutrophil influx. This up-regulation suggests that host-derived lipids act as mediators of mucosal immunity in CRS. Further study is necessary to determine if such antimicrobial lipids function alone or synergistically with antibacterial peptides in conferring such inherent microbicidal properties.

Relation of Plasma Lipids to Alzheimer Disease and Vascular Dementia

PubMed Central

Reitz, Christiane; Tang, Ming-Xin; Luchsinger, Jose; Mayeux, Richard

2009-01-01

Background The relation between plasma lipid levels and Alzheimer disease (AD) and vascular dementia (VaD), and the impact of drugs to lower lipid levels remains unclear. Objective To investigate the relation between plasma lipid levels and the risk of AD and VaD and the impact of drugs to lower lipid levels on this relationship. Design and Setting Cross-sectional and prospective community-based cohort studies. Participants Random sample of 4316 Medicare recipients, 65 years and older, residing in northern Manhattan, NY. Main Outcome Measures Vascular dementia and AD according to standard criteria. Results Elevated levels of non–high-density lipoprotein (HDL-C) and low-density lipoprotein cholesterol (LDL-C) and decreased levels of HDL-C were weak risk factors for VaD in either cross-sectional or prospective analyses. Higher levels of total cholesterol were associated with a decreased risk of incident AD after adjustment for demographics, apolipoprotein E genotype, and cardiovascular risk factors. Treatment with drugs to lower lipid levels did not change the disease risk of either disorder. Conclusions We found a weak relation between non–HDL-C, LDL-C, and HDL-C levels and the risk of VaD. Lipid levels and the use of agents to lower them do not seem to be associated with the risk of AD. PMID:15148148

Recovery of lipid metabolic alterations in hepatitis C patients after viral clearance: Incomplete restoration with accelerated ω-oxidation.

PubMed

Chang, Su-Wei; Cheng, Mei-Ling; Shiao, Ming-Shi; Yeh, Chau-Ting; Wang, Chao-Hung; Fan, Chun-Ming; Chiu, Cheng-Tang; Chang, Ming-Ling

2018-03-02

How hepatitis C virus (HCV)-associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. The aforementioned recovery pattern was investigated. In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Selection and evaluation of CO2 tolerant indigenous microalga Scenedesmus dimorphus for unsaturated fatty acid rich lipid production under different culture conditions.

PubMed

Vidyashankar, S; Deviprasad, K; Chauhan, V S; Ravishankar, G A; Sarada, R

2013-09-01

Five indigenous microalgal strains of Scenedesmus, Chlorococcum, Coelastrum, and Ankistrodesmus genera, isolated from Indian fresh water habitats, were studied for carbon-dioxide tolerance and its effect on growth, lipid and fatty acid profile. Scenedesmus dimorphus strain showed maximum growth (1.5 g/L) and lipid content (17.83% w/w) under CO2 supplementation, hence selected for detailed evaluation. The selected strain was alkaline adapted but tolerated (i) wide range of pH (5-11); (ii) elevated salinity levels (up to 100 mM, NaCl) with low biomass yields and increased carotenoids (19.34 mg/g biomass); (iii) elevated CO2 levels up to 15% v/v with enhancement in specific growth rate (0.137 d(-1)), biomass yield (1.57 g/L), lipid content (19.6% w/w) and CO2 biofixation rate (0.174 g L(-1) d(-1)). Unsaturated fatty acid content (alpha linolenic acid) increased with CO2 supplementation in the strain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

PubMed Central

Markworth, James F.; Vella, Luke; Lingard, Benjamin S.; Tull, Dedreia L.; Rupasinghe, Thusitha W.; Sinclair, Andrew J.; Maddipati, Krishna Rao

2013-01-01

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a biological active inflammatory resolution program, regulated by proresolving lipid mediators during postexercise recovery. PMID:24089379

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects

PubMed Central

Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J.; Musi, Nicolas

2018-01-01

Objective The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Research design and methods Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. Results The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. Conclusions In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals. PMID:29649324

A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

PubMed

Liang, Hanyu; Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J; Musi, Nicolas

2018-01-01

The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

Elevated host lipid metabolism revealed by iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid of tuberculous meningitis patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mu, Jun; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing; Chongqing Key Laboratory of Neurobiology, Chongqing

Purpose: Tuberculous meningitis (TBM) remains to be one of the most deadly infectious diseases. The pathogen interacts with the host immune system, the process of which is largely unknown. Various cellular processes of Mycobacterium tuberculosis (MTB) centers around lipid metabolism. To determine the lipid metabolism related proteins, a quantitative proteomic study was performed here to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n = 12) and healthy controls (n = 12). Methods: CSF samples were desalted, concentrated, labelled with isobaric tags for relative and absolute quantitation (iTRAQ™), and analyzed by multi-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene ontology andmore » proteomic phenotyping analysis of the differential proteins were conducted using Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. ApoE and ApoB were selected for validation by ELISA. Results: Proteomic phenotyping of the 4 differential proteins was invloved in the lipid metabolism. ELISA showed significantly increased ApoB levels in TBM subjects compared to healthy controls. Area under the receiver operating characteristic curve analysis demonstrated ApoB levels could distinguish TBM subjects from healthy controls and viral meningitis subjects with 89.3% sensitivity and 92% specificity. Conclusions: CSF lipid metabolism disregulation, especially elevated expression of ApoB, gives insights into the pathogenesis of TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other center nervous system infectious diseases is required for successful clinical translation. - Highlights: • The first proteomic study on the cerebrospinal fluid of tuberculous meningitis patients using iTRAQ. • Identify 4 differential proteins invloved in the lipid metabolism. • Elevated expression of ApoB gives insights into the pathogenesis of TBM.« less

Steroidal compounds in commercial parenteral lipid emulsions.

PubMed

Xu, Zhidong; Harvey, Kevin A; Pavlina, Thomas; Dutot, Guy; Hise, Mary; Zaloga, Gary P; Siddiqui, Rafat A

2012-08-01

Parenteral nutrition lipid emulsions made from various plant oils contain steroidal compounds, called phytosterols. During parenteral administration of lipid emulsions, phytosterols can reach levels in the blood that are many fold higher than during enteral administration. The elevated phytosterol levels have been associated with the development of liver dysfunction and the rare development of liver failure. There is limited information available in the literature related to phytosterol concentrations in lipid emulsions. The objective of the current study was to validate an assay for steroidal compounds found in lipid emulsions and to compare their concentrations in the most commonly used parenteral nutrition lipid emulsions: Liposyn(®) II, Liposyn(®) III, Lipofundin(®) MCT, Lipofundin(®) N, Structolipid(®), Intralipid(®), Ivelip(®) and ClinOleic(®). Our data demonstrates that concentrations of the various steroidal compounds varied greatly between the eight lipid emulsions, with the olive oil-based lipid emulsion containing the lowest levels of phytosterols and cholesterol, and the highest concentration of squalene. The clinical impression of greater incidences of liver dysfunction with soybean versus MCT/LCT and olive/soy lipid emulsions may be reflective of the levels of phytosterols in these emulsions. This information may help guide future studies and clinical care of patients with lipid emulsion-associated liver dysfunction.

Steroidal Compounds in Commercial Parenteral Lipid Emulsions

PubMed Central

Xu, Zhidong; Harvey, Kevin A.; Pavlina, Thomas; Dutot, Guy; Hise, Mary; Zaloga, Gary P.; Siddiqui, Rafat A.

2012-01-01

Parenteral nutrition lipid emulsions made from various plant oils contain steroidal compounds, called phytosterols. During parenteral administration of lipid emulsions, phytosterols can reach levels in the blood that are many fold higher than during enteral administration. The elevated phytosterol levels have been associated with the development of liver dysfunction and the rare development of liver failure. There is limited information available in the literature related to phytosterol concentrations in lipid emulsions. The objective of the current study was to validate an assay for steroidal compounds found in lipid emulsions and to compare their concentrations in the most commonly used parenteral nutrition lipid emulsions: Liposyn® II, Liposyn® III, Lipofundin® MCT, Lipofundin® N, Structolipid®, Intralipid®, Ivelip® and ClinOleic®. Our data demonstrates that concentrations of the various steroidal compounds varied greatly between the eight lipid emulsions, with the olive oil-based lipid emulsion containing the lowest levels of phytosterols and cholesterol, and the highest concentration of squalene. The clinical impression of greater incidences of liver dysfunction with soybean versus MCT/LCT and olive/soy lipid emulsions may be reflective of the levels of phytosterols in these emulsions. This information may help guide future studies and clinical care of patients with lipid emulsion-associated liver dysfunction. PMID:23016123

Subclinical hypothyroidism, lipid metabolism and cardiovascular disease.

PubMed

Delitala, Alessandro P; Fanciulli, Giuseppe; Maioli, Margherita; Delitala, Giuseppe

2017-03-01

Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

PubMed

Uno, Kenji; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Hasegawa, Yutaka; Sawada, Shojiro; Kaneko, Keizo; Ono, Hiraku; Asano, Tomoichiro; Oka, Yoshitomo; Katagiri, Hideki

2015-08-13

Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant-negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and β-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia.

The effect of melatonin on eye lens of rats exposed to ultraviolet radiation.

PubMed

Anwar, M M; Moustafa, M A

2001-05-01

We investigated the influence of exogenously administered melatonin on adult rats eye lenses exposed to ultraviolet radiation (UV) A and B ranging from 356-254 nm irradiation at 8 microW/cm(2). Rats exposed to this range of UV for 15 min for one week showed a significant (P<0.05) reduction in antioxidant enzymes activities; superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and elevated (P<0.001) lipid peroxidation served as an index of cellular damage by free radicals. UV-radiation significantly (P<0.001) elevated calcium ions (Ca(2+)) and lactate dehydrogenase (LDH) activity in lenses. Depleting animals of their stores of important intracellular antioxidant and elevating lenticular Ca(2+) by UV irradiation, may be the main cause of lens opacification. Melatonin injection with radiation significantly reduced (P<0.05) lipid peroxidation, Ca(2+) and (P<0.001) for LDH. When melatonin was injected after radiation, SOD and GSH-Px enzyme activities increased significantly (P<0.01), and lipid peroxidation, Ca(2+) levels and LDH activities were reduced significantly. Melatonin injection after UV radiation was as effective as melatonin treatment concurrent with UV irradiation. We conclude that melatonin may protect the eye lens from the damaging effects of UV exposure, and its actions protect lens from oxidative stress, elevating Ca(2+) levels, which are considered as an important causes of cataractogenesis.

[Lipid peroxidation and the system of antioxidant protection in rats following a 13-day space flight on the Kosmos-1887 biosatellite].

PubMed

Markin, A A; Delenian, N V

1992-01-01

After a 13-day space mission, in the rats flown on Cosmos-1887 biosatellite the parameters of lipid peroxidation and antioxidant defense system--the contents of diene conjugates, malonic dialdehyde, Schiff bases, tocopherol, total antioxidant activity (in blood plasma only), antioxidant enzyme activity (in tissues only)--superoxide dismutase, catalase, glutathio peroxidase, glutathio reductase have been measured in the blood plasma, myocardium, skeletal muscles and liver. The liver level of diene conjugates, Schiff bases and tocopherol decreased, and an activity of superoxide dismutase and catalase increased. In the skeletal muscles there was an elevation of diene conjugate contents followed by the decreases in malonic dialdehyde and superoxide dismutase activity. In rat myocardium, superoxide dismutase activity and tocopherol levels increased significantly. In the blood plasma the levels of tocopherol, malonic dialdehyde and total antioxidant activity were elevated. It is concluded that the observed changes in lipid peroxidation developed probably in response to an effect of the last dynamic stage of space flight and during re-adapting to the Earth environments.

Regulation of GPR119 receptor activity with endocannabinoid-like lipids.

PubMed

Syed, Samreen K; Bui, Hai Hoang; Beavers, Lisa S; Farb, Thomas B; Ficorilli, James; Chesterfield, Amy K; Kuo, Ming-Shang; Bokvist, Krister; Barrett, David G; Efanov, Alexander M

2012-12-15

The GPR119 receptor plays an important role in the secretion of incretin hormones in response to nutrient consumption. We have studied the ability of an array of naturally occurring endocannabinoid-like lipids to activate GPR119 and have identified several lipid receptor agonists. The most potent receptor agonists identified were three N-acylethanolamines: oleoylethanolamine (OEA), palmitoleoylethanolamine, and linoleylethanolamine (LEA), all of which displayed similar potency in activating GPR119. Another lipid, 2-oleoylglycerol (2-OG), also activated GPR119 receptor but with significantly lower potency. Endogenous levels of endocannabinoid-like lipids were measured in intestine in fasted and refed mice. Of the lipid GPR119 agonists studied, the intestinal levels of only OEA, LEA, and 2-OG increased significantly upon refeeding. Intestinal levels of OEA and LEA in the fasted mice were low. In the fed state, OEA levels only moderately increased, whereas LEA levels rose drastically. 2-OG was the most abundant of the three GPR119 agonists in intestine, and its levels were radically elevated in fed mice. Our data suggest that, in lean mice, 2-OG and LEA may serve as physiologically relevant endogenous GPR119 agonists that mediate receptor activation upon nutrient uptake.

Dietary restriction causes chronic elevation of corticosterone and enhances stress response in red-legged kittiwake chicks

USGS Publications Warehouse

Kitaysky, A.S.; Kitaiskaia, E.V.; Wingfield, J.C.; Piatt, John F.

2001-01-01

Release of corticosterone in hungry kittiwake chicks facilitates begging and allows them to restore depleted energy reserves by increasing parental food provisioning. However, in order to avoid detrimental effects of chronic elevation of corticosterone, chicks might suppress adrenocortical activity in response to prolonged food shortages. In this study we examined temporal dynamics of corticosterone release in red-legged kittiwake (Rissa brevirostris) chicks exposed to prolonged restrictions in energy content and/or nutritional quality (low versus high lipid content) of their food. Starting at the age of 15 days, chicks were fed either high- or low-lipid fish at 40%, 65%, and 100% of ad libitum energy intake. Body mass measurements and baseline plasma samples were taken on a weekly basis after beginning of the treatment. After 3 weeks of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where in addition to a baseline sample, three plasma samples were taken at intervals up to 50 min. We found that food-restricted chicks had lower body mass, chronically (during 2-3 weeks) elevated baseline and higher acute stress-induced levels of corticosterone compared to chicks fed ad libitum. Low lipid content of food further exacerbated these effects. An increase in baseline levels of corticosterone was observed within a week after energy requirements of food-restricted chicks exceeded their daily energy intake. A tendency for suppression of adrenocortical activity was observed in treatments fed low-lipid diets only at the end of the experiment. We suggest that nest-bound chicks, if food-stressed, might suffer deleterious effects of chronic elevation of corticosterone.

Dyslipidemia and Auditory Function

PubMed Central

Evans, M. Bradley; Tonini, Ross; Shope, Cynthia Do; Oghalai, John S.; Jerger, James F.; Insull, William; Brownell, William E.

2013-01-01

The relationship between dyslipidemia and hearing is unclear. This study was conducted to investigate whether elevated serum lipid levels impact auditory function in humans and in guinea pigs. In the human study, a cross-sectional study of 40 volunteers with dyslipidemia was conducted. Pure tone thresholds, distortion product otoacoustic emissions, and lipid profiles were analyzed. When controlled for patient age and sex, we found that elevated triglycerides were associated with reduced hearing. In the guinea pig study, a prospective study of animals fed a high-fat diet for 14 weeks was conducted. Although the high-fat diet led to a dramatic elevation in the average weight and total cholesterol in all animals (from 61 to 589 mg/dl), there were no meaningful changes in distortion product otoacoustic emission magnitudes. These results suggest that whereas chronic dyslipidemia associated with elevated triglycerides may reduce auditory function, short-term dietary changes may not. PMID:16868509

Triglycerides: A reappraisal.

PubMed

Wiesner, Philipp; Watson, Karol E

2017-08-01

Elevated cholesterol levels are clearly independently associated with adverse cardiovascular events. Another class of lipid particles, triglycerides, is also abundant in the human body and has been found in atherosclerotic plaques. Recent observational studies have demonstrated an association between elevated triglyceride levels and increased risk for future cardiovascular events. With this knowledge and the discovery of effective agents to lower triglyceride levels, the management of triglycerides is currently undergoing a renaissance. Unfortunately, no randomized, controlled clinical trials have been completed to date, proving that lowering triglycerides will reduce cardiovascular events. In this review we highlight some of the evidence that led to this stage and discuss the current data on pharmacologic intervention of triglyceride levels and the effect on clinical outcomes. Lastly, we want to give the reader insight on what the most recent lipid guidelines state about clinical triglyceride management, mention new pharmacological agents, and highlight the clinical evidence for safe and effective lowering of triglycerides levels with life style modification. Copyright © 2017. Published by Elsevier Inc.

Dioxins and dioxin-like chemicals in blood and semen of American Vietnam veterans from the state of Michigan.

PubMed

Schecter, A; McGee, H; Stanley, J S; Boggess, K; Brandt-Rauf, P

1996-12-01

This exposure assessment pilot study tested the hypothesis that elevated blood levels of the dioxin congener 2,3,7,8-TCDD ("TCDD"), due to Agent Orange exposure, in American Vietnam veterans could be demonstrated two to three decades after Vietnam service. A second objective was to determine if dioxins, including TCDD, are present in the semen of adult males. In the early 1990s, blood samples from 50 Vietnam veterans and three pooled semen samples from 17 of them were analyzed by high-resolution gas chromatography-mass spectroscopy for dioxins, dibenzofurans, and the dioxin-like PCBs. Fifty volunteers from the Michigan Vietnam veteran bonus list, which documented Vietnam service, were invited to participate based on their self-reported exposure to Agent Orange in Vietnam. Screening of military and medical records was performed by an epidemiologist and a physician to assure that Agent Orange exposure was possible based on job description, location of service in Vietnam, and military Agent Orange spray records. Elevated 2,3,7,8-TCDD levels, over 20 ppt on a lipid basis, could still be detected in six of the 50 veterans in this nonrandomly selected group. The dioxin and dibenzofuran congeners commonly found in the U.S. population, including TCDD, were also detected in the three pooled semen samples. Quantification and comparison on a lipid basis were not possible due to low lipid concentrations where levels were below the detection limit. Therefore, semen samples were measured and reported on a wet-weight basis. Elevated blood TCDD levels, probably related to Agent Orange exposure, can be detected between two and three decades after potential exposure in some American veterans. Original levels were estimated to be 35-1,500-fold greater that that of the general population (4 ppt, lipid) at the time of exposure. In addition, the detection of dioxins in semen suggests a possible mechanism for male-mediated adverse reproductive outcomes following Agent Orange or other dioxin exposure.

Changes in the serum lipid profile in man during 24 months of arctic residence.

PubMed

Bojko, E R; Larsen, T S

1999-07-01

The influence of the severe climate and geographical conditions at the Svalbard archipelago (78-79 degrees N) on serum lipid levels were measured in Caucasian miners who had arrived from the southern part of Ukraine and Russia (48 degrees N). The persons included in the study were randomly divided in five groups according to their time of living (1, 3, 6, 12 and 24 months) at Svalbard. Blood sampling took place during a two week period in January, when the Svalbard archipelago is into its polar night. General elevated levels of triglycerides were found in group I-III (1, 3 and 6 months stay), whereas the values measured in group IV and V (12 and 24 months stay) were somewhat lower. This apparent decline in triglycerides was paralelled by generally elevated levels of HDL cholesterol. The serum level of phospholipids was similar in all groups. All the level of free fatty acids was apparently higher in groups IV and V, particularly 18:3 and 16:1. These results may be indicative of a rise in triglyceride consumption after about a 12 month stay in the archipelago. Besides, the elevated levels of 18:3 and 16:1 fatty acids imply dietary modifications of the serum fatty acids.

Racial differences in levels of serum lipids and effects of exposure to persistent organic pollutants on lipid levels in residents of Anniston, Alabama.

PubMed

Aminov, Zafar; Haase, Richard; Olson, James R; Pavuk, Marian; Carpenter, David O

2014-12-01

Serum lipid levels are major risk factors for cardiovascular disease. In addition to diet, exercise, genetics, age and race, serum concentrations of persistent organic pollutants (POPs) influence concentrations of serum lipids. We investigated associations between fasting concentrations of 35 polychlorinated biphenyl (PCB) congeners and nine organochlorine pesticides in relation to total serum lipids, total cholesterol, low-density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides in 525 Caucasian and African American residents of Anniston, Alabama, who were not on any lipid-lowering medication. In Model 1, data were adjusted for age, age quadratic, gender, BMI, alcohol consumption, smoking and exercise, while in Model 2, additional adjustment was done for other POPs. As compared to Caucasians, African Americans had lower levels of total lipids and triglycerides with higher concentrations of HDL cholesterol, but higher concentrations of PCBs and pesticides. Total pesticides were more strongly associated with elevations in serum lipids than were total PCBs, and the associations were stronger in African Americans. Total DDTs were not associated with serum lipids after adjustment for other POPs in either racial group, while the strongest positive associations were seen for hexachlorobenzene (HCB) in both racial groups. Racial differences in lipid profiles, concentrations of POPs and associations between POP concentrations and serum lipids are relevant to racial differences in rates of cardiovascular disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dietary docosahexaenoic acid-induced generation of liver lipid peroxides is not suppressed further by elevated levels of glutathione in ODS rats.

PubMed

Sekine, Seiji; Kubo, Kazuhiro; Tadokoro, Tadahiro; Saito, Morio

2006-04-01

We examined the effects of ascorbic acid (AsA) and glutathione (GSH; experiment 1) and of GSH in acetaminophen-fed rats (experiment 2) on dietary docosahexaenoic acid (DHA)-induced tissue lipid peroxidation. In experiment 1, AsA-requiring Osteogenic Disorder Shionogi/Shi-od/od (ODS) rats were fed soybean protein diets containing DHA (10.0% total energy) and AsA at 50 (low) or 300 (normal) mg/kg without (low) or with (normal) methionine at 2 g/kg for 32 d. In experiment 2, ODS rats were fed diets containing DHA (7.8% total energy) and acetaminophen (4 g/kg) with different levels of dietary methionine (low, moderate, high, and excessive at 0, 3, 6, and 9 g/kg, respectively) for 30 d. Tissue lipid peroxides and antioxidant levels were determined. In experiment 1, liver lipid peroxide levels in the low-AsA group were lower than those in the normal-AsA group, but kidney and testis lipid peroxide levels in the low-AsA group were higher than those in the normal-AsA group. Dietary methionine tended to decrease tissue lipid peroxide levels but did not decrease vitamin E (VE) consumption. In experiment 2, a high level of methionine (6 g/kg) decreased liver lipid peroxide levels and VE consumption. However, generation of tissue lipid peroxides and VE consumption were not decreased further by a higher dose of methionine (9 g/kg). Higher than normal levels of dietary methionine are not necessarily associated with decreased dietary DHA-induced generation of tissue lipid peroxides and VE consumption except that the GSH requirement is increased in a condition such as acetaminophen feeding.

Loss of CTRP1 disrupts glucose and lipid homeostasis

PubMed Central

Rodriguez, Susana; Lei, Xia; Petersen, Pia S.; Tan, Stefanie Y.; Little, Hannah C.

2016-01-01

C1q/TNF-related protein 1 (CTRP1) is a conserved plasma protein of the C1q family with notable metabolic and cardiovascular functions. We have previously shown that CTRP1 infusion lowers blood glucose and that transgenic mice with elevated circulating CTRP1 are protected from diet-induced obesity and insulin resistance. Here, we used a genetic loss-of-function mouse model to address the requirement of CTRP1 for metabolic homeostasis. Despite similar body weight, food intake, and energy expenditure, Ctrp1 knockout (KO) mice fed a low-fat diet developed insulin resistance and hepatic steatosis. Impaired glucose metabolism in Ctrp1 KO mice was associated with increased hepatic gluconeogenic gene expression and decreased skeletal muscle glucose transporter glucose transporter 4 levels and AMP-activated protein kinase activation. Loss of CTRP1 enhanced the clearance of orally administered lipids but did not affect intestinal lipid absorption, hepatic VLDL-triglyceride export, or lipoprotein lipase activity. In contrast to triglycerides, hepatic cholesterol levels were reduced in Ctrp1 KO mice, paralleling the reduced expression of cholesterol synthesis genes. Contrary to expectations, when challenged with a high-fat diet to induce obesity, Ctrp1 KO mice had increased physical activity and reduced body weight, adiposity, and expression of lipid synthesis and fibrotic genes in adipose tissue; these phenotypes were linked to elevated FGF-21 levels. Due in part to increased hepatic AMP-activated protein kinase activation and reduced expression of lipid synthesis genes, Ctrp1 KO mice fed a high-fat diet also had reduced liver and serum triglyceride and cholesterol levels. Taken together, these results provide genetic evidence to establish the significance of CTRP1 to systemic energy metabolism in different metabolic and dietary contexts. PMID:27555298

The relation among steroid hormone levels, lipid profile and menopausal symptom severity.

PubMed

Kaya, Cihan; Cengiz, Hüseyin; Yeşil, Ali; Ekin, Murat; Yaşar, Levent

2017-12-01

Many postmenopausal women experience hot flashes, night sweats, non-specific emotional and psychological distresses. Our aim was to investigate the relation among steroid hormone levels, lipid profile and menopausal symptom severity using the menopause rating scale (MRS). A cross-sectional study was performed at our outpatient clinic with natural postmenopausal women. A total of 444 women were included in this study. The basic characteristics of the study population, such as age, gravidity, parity, time to menopause onset and body mass index (BMI) were recorded. Venous blood samples were collected from subjects after overnight fasting. The levels of high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total cholesterol, triglyceride (TG), fasting plasma glucose, C-reactive protein, thyroid-stimulating hormone (TSH), cortisol, estradiol (E2), progesterone, testosterone and dehydroepiandrostenedione sulfate (DHEA-S) were analyzed. The MRS questionnaire validated for the Turkish population was used to assess the menopausal symptoms. There was a statistically significant difference between mild and severe total symptom scores for TG, and elevated TG levels were observed in the severe group (p = 0.04). Elevated testosterone levels were observed with severe psychological symptom and total symptom scores. There were significant differences in progesterone level in psychological, urogenital, and total scores and lower levels were seen in severe symptom groups. There was a significant negative correlation between urogenital symptom scores and progesterone levels (p < 0.001). Elevated levels of testosterone were related to severe psychological symptom and total menopausal symptom scores. A decrease in progesterone levels was related to high psychological, urogenital and total menopausal symptom scores. Elevated TG levels were also related to the total severe symptom scores.

Olive Leaf Extract Elevates Hepatic PPAR α mRNA Expression and Improves Serum Lipid Profiles in Ovariectomized Rats.

PubMed

Yoon, Leena; Liu, Ya-Nan; Park, Hyunjin; Kim, Hyun-Sook

2015-07-01

We hypothesized that olive leaf extract might alleviate dyslipidemia resulting from estrogen deficiency. Serum lipid profile and mRNA expression of the related genes in the liver and adipose tissue were analyzed after providing olive leaf extract (200 or 400 mg/kg body weight; n=7 for each group) to ovariectomized rats for 10 weeks. After 10 weeks' administration, the rats in the olive leaf extract-administered groups showed significantly lower levels of serum triglyceride and very-low-density lipoprotein (VLDL)-cholesterol compared with the rats in the control group, whereas the administration of olive leaf extract did not significantly change the elevated low-density lipoprotein cholesterol levels. In addition, administration of high dose of olive leaf extract significantly decreased the liver triglyceride and increased serum estradiol levels. mRNA expressions of peroxisome proliferator-activated receptor alpha (PPAR α) and acyl-CoA oxidase (ACO) were not affected by ovariectomy, however, administration of olive leaf extract significantly increased both PPAR α and ACO mRNA expression. Expression of adiponectin mRNA in adipose tissue was significantly decreased in the ovariectomized control group. Rats administered low-dose olive leaf extract showed significantly elevated adiponectin mRNA expression compared with rats in the ovariectomized control group. Even though dose-dependent effects were not observed in most of the measurements, these results suggest that genes involved in lipid metabolism may be regulated by olive leaf extract administration in ovariectomized rats.

Atorvastatin Combined Nitroglycerin Therapy Confer Additive Effects on Rabbits with Dyslipidemia.

PubMed

Yang, Fang; Wang, Jindong; Li, Fei; Cui, Lei

2016-06-01

Endogenous nitric oxide (NO) is beneficial for inhibiting Rho-associated kinase 2 (ROCK2) expression. However, the effect of exogenous NO on ROCK2 expression is less investigated. Rabbits with dyslipidemia were produced and randomly assigned into untreated, atorvastatin, nitroglycerin and combined groups (n=10 in each group). Medication therapy was lasted for 2 weeks. Parameters of interest including lipid profiles, liver enzyme, C-reactive protein (CRP), malondialdehyde (MDA), NO level and ROCK2 level were assessed at baseline, 2 weeks of dyslipidemia establishment and 2 weeks of medication treatment. No significant difference in parameters was found between groups at baseline. With 2 weeks of dyslipidemia establishment, as compared to baseline, serum levels of lipid profiles, CRP and MDA were profoundly elevated. In addition, reduced NO generation and enhanced ROCK2 expression were also observed. With 2 weeks of medication therapy, lipid profiles, systemic inflammation (reflected as serum CRP level) and oxidation (reflected as serum MDA level) were improved in the atorvastatin and combined groups but not in the nitroglycerin group (P<0.05). Furthermore, increased NO production in accompany with reduced ROCK2 expression were observed in both the atorvastatin and nitroglycerin groups, and these benefits were further enhanced by combined therapy (P<0.05). No liver enzymes elevation was observed after 2 weeks of medication therapy. Nitroglycerin-derived exogenous NO could effectively inhibit ROCK2 expression in rabbits with dyslipidemia which is independent of lipid-modification, and these efficacies could be enhanced by statins therapy. © Georg Thieme Verlag KG Stuttgart · New York.

[The significance of fenofibrate in the therapy of atherogenic dyslipoproteinaemia].

PubMed

Kucera, M; Oravec, S; Ocadlík, I

2010-08-01

There are accepted the lipid levels goals in all world, which are needed to achievement in primary and secondary prevention. Despite efficacy of current standards of care (including achievement of LDL-C, blood pressure and blood sugar goals), patients with atherogenic dyslipidemia (DLP) (high TG levels, low HDL-C, high apolipoprotein B and small dense LDL-particles), which is common in patients with diabetes melitus (DM), metabolic syndrome or cardiovascular diseases (KVD), remain exposed to a high residual risk of major cardiovascular events and microvascular complications. Statin therapy does not adequately address vascular risk asociated with elevated triglycerides (TG) and low HDL-C levels. As ACCORD lipid trial last time shows, the addition of lipid-modifying activity of fenofibrate to statin therapy benefited only certain subgroups of patients at increased cardiometabolic risk.

Effect of Mucuna pruriens on semen profile and biochemical parameters in seminal plasma of infertile men.

PubMed

Ahmad, Mohammad Kaleem; Mahdi, Abbas Ali; Shukla, Kamla Kant; Islam, Najmul; Jaiswar, Shyam Pyari; Ahmad, Sohail

2008-09-01

To investigate the impact of Mucuna pruriens seeds on semen profiles and biochemical levels in seminal plasma of infertile men. Prospective study. Departments of Biochemistry and Obstetrics and Gynecology, King George's Medical University, Lucknow, India. Sixty normal healthy fertile men (controls) and 60 men undergoing infertility screening. High-performance liquid chromatography assay procedure for quantitation of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma, namely lipids, fructose, and vitamin C, were estimated by standard spectrophotometric procedures. Before and after the treatment, seminal plasma lipid profile, lipid peroxide, fructose, and antioxidant vitamin levels were measured. Treatment with M. pruriens significantly inhibited lipid peroxidation, elevated spermatogenesis, and improved sperm motility. Treatment also recovered the levels of total lipids, triglycerides, cholesterol, phospholipids, and vitamin A, C, and E and corrected fructose in seminal plasma of infertile men. Treatment with M. pruriens increased sperm concentration and motility in all the infertile study groups. Oligozoospermic patients recovered sperm concentration significantly, but sperm motility was not restored to normal levels in asthenozoospermic men. Furthermore, in the seminal plasma of all the infertile groups, the levels of lipids, antioxidant vitamins, and corrected fructose were recovered after a decrease in lipid peroxides after treatment. The present study is likely to open new vistas on the possible role of M. pruriens seed powder as a restorative and invigorating agent for infertile men.

Homocysteine regulates fatty acid and lipid metabolism in yeast

PubMed Central

Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O.; Wolinski, Heimo; Rechberger, Gerald N.; Tehlivets, Oksana

2018-01-01

S-Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S-adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. PMID:29414770

Cholesterol Metabolism in CKD

PubMed Central

Reiss, Allison B.; Voloshyna, Iryna; DeLeon, Joshua; Miyawaki, Nobuyuki; Mattana, Joseph

2015-01-01

Patients with chronic kidney disease (CKD) have a substantial risk of developing coronary artery disease. Traditional cardiovascular disease (CVD) risk factors such as hypertension and hyperlipidemia do not adequately explain the high prevalence of CVD in CKD. Both CVD and CKD are inflammatory states and inflammation adversely impacts lipid balance. Dyslipidemia in CKD is characterized by elevated triglycerides and high density lipoprotein that is both decreased and dysfunctional. This dysfunctional high density lipoprotein becomes pro-inflammatory and loses its atheroprotective ability to promote cholesterol efflux from cells, including lipid-overloaded macrophages in the arterial wall. Elevated triglycerides result primarily from defective clearance. The weak association between low density lipoprotein cholesterol level and coronary risk in CKD has led to controversy over the usefulness of statin therapy. This review examines disrupted cholesterol transport in CKD, presenting both clinical and pre-clinical evidence of the impact of the uremic environment on vascular lipid accumulation. Preventative and treatment strategies are explored. PMID:26337134

Increased plasma lipid levels exacerbate muscle pathology in the mdx mouse model of Duchenne muscular dystrophy.

PubMed

Milad, Nadia; White, Zoe; Tehrani, Arash Y; Sellers, Stephanie; Rossi, Fabio M V; Bernatchez, Pascal

2017-09-12

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin expression and leads to severe ambulatory and cardiac function decline. However, the dystrophin-deficient mdx murine model of DMD only develops a very mild form of the disease. Our group and others have shown vascular abnormalities in animal models of MD, a likely consequence of the fact that blood vessels express the same dystrophin-associated glycoprotein complex (DGC) proteins as skeletal muscles. To test the blood vessel contribution to muscle damage in DMD, mdx 4cv mice were given elevated lipid levels via apolipoprotein E (ApoE) gene knockout combined with normal chow or lipid-rich Western diets. Ambulatory function and heart function (via echocardiogram) were assessed at 4 and 7 months of age. After sacrifice, muscle histology and aortic staining were used to assess muscle pathology and atherosclerosis development, respectively. Plasma levels of total cholesterol, high-density lipoprotein (HDL), triglycerides, and creatine kinase (CK) were also measured. Although there was an increase in left ventricular heart volume in mdx-ApoE mice compared to that in mdx mice, parameters of heart function were not affected. Compared with wild-type and ApoE-null, only mdx-ApoE KO mice showed significant ambulatory dysfunction. Despite no significant difference in plasma CK, histological analyses revealed that elevated plasma lipids in chow- and Western diet-fed mdx-ApoE mice was associated with severe exacerbation of muscle pathology compared to mdx mice: significant increase in myofiber damage and fibrofatty replacement in the gastrocnemius and triceps brachii muscles, more reminiscent of human DMD pathology. Finally, although both ApoE and mdx-ApoE groups displayed increased plasma lipids, mdx-ApoE exhibited atherosclerotic plaque deposition equal to or less than that of ApoE mice. Since others have shown that lipid abnormalities correlate with DMD severity, our data suggest that plasma lipids could be primary contributors to human DMD severity and that the notoriously mild phenotype of mdx mice might be attributable in part to their endogenously low plasma lipid profiles. Hence, DMD patients may benefit from lipid-lowering and vascular-targeted therapies.

Telomerase reverse transcriptase (TERT) - enhancer of zeste homolog 2 (EZH2) network regulates lipid metabolism and DNA damage responses in glioblastoma.

PubMed

Ahmad, Fahim; Patrick, Shruti; Sheikh, Touseef; Sharma, Vikas; Pathak, Pankaj; Malgulwar, Prit Benny; Kumar, Anupam; Joshi, Shanker Datt; Sarkar, Chitra; Sen, Ellora

2017-12-01

Elevated expression of enhancer of zeste homolog 2 (EZH2), a histone H3K27 methyltransferase, was observed in gliomas harboring telomerase reverse transcriptase (TERT) promoter mutations. Given the known involvement of TERT and EZH2 in glioma progression, the correlation between the two and subsequently its involvement in metabolic programming was investigated. Inhibition of human telomerase reverse transcriptase either pharmacologically or through genetic manipulation not only decreased EZH2 expression, but also (i) abrogated FASN levels, (ii) decreased de novo fatty acid accumulation, and (iii) increased ataxia-telangiectasia-mutated (ATM) phosphorylation levels. Conversely, diminished TERT and FASN levels upon siRNA-mediated EZH2 knockdown indicated a positive correlation between TERT and EZH2. Interestingly, ATM kinase inhibitor rescued TERT inhibition-mediated decrease in FASN and EZH2 levels. Importantly, TERT promoter mutant tumors exhibited greater microsatellite instability, heightened FASN levels and lipid accumulation. Coherent with in vitro findings, pharmacological inhibition of TERT by costunolide decreased lipid accumulation and elevated ATM expression in heterotypic xenograft glioma mouse model. By bringing TERT-EZH2 network at the forefront as driver of dysregulated metabolism, our findings highlight the non-canonical but distinct role of TERT in metabolic reprogramming and DNA damage responses in glioblastoma. © 2017 International Society for Neurochemistry.

Ambulatory blood pressure and blood lipids in a multiethnic sample of healthy adults.

PubMed

James, Gary D; Van Berge-Landry, Helene M; Morrison, Lynn A; Reza, Angela M; Nicolaisen, Nicola M; Bindon, James R; Brown, Daniel E

2013-01-01

Elevated blood pressure (BP), elevated serum cholesterol, and aberrant lipoprotein fractions (low levels of high-density lipoprotein (HDL) and high levels of low-density lipoprotein fractions and triglycerides) have all been used as measures that assess the "metabolic syndrome" and more recently in indexes of allostatic load, which are designed to assess the degree of integrated metabolic pathology. While there are ample data regarding the interrelationships of these measures in various pathophysiological settings, there are limited data regarding the interrelationship of ambulatory BP (ABP) and blood lipids in healthy subjects. The present study evaluates ABP-blood lipid relationships in a multiethnic sample of healthy adults. The subjects were 37 men (age = 40.9 ± 10.7 years) and 42 women (age = 35.8 ± 10.4 years) who were employed as hotel workers in Hawaii. Each wore an ABP monitor for one midweek workday and had pressures averaged in three daily microenvironments (work, home, and during sleep). They also had fasting blood samples taken for lipid profiling. Multivariate analysis of covariance shows that there was a strong inverse relationship between HDL and both systolic (P < 0.006) and diastolic (P < 0.006) BP, overall and in each microenvironment, but no statistically significant relationships with other lipid measures. These results suggest lipids and BP do not act as a group in healthy adults but that higher HDL is associated with lower BP. This latter finding is consistent with research that shows that HDL promotes vasodilation via its effect on endothelial nitric oxide synthase. Copyright © 2013 Wiley Periodicals, Inc.

Non-high-density lipoprotein cholesterol and other lipid indices vs elevated glucose risk in Arab adolescents.

PubMed

Al-Daghri, Nasser M; Aljohani, Naji J; Al-Attas, Omar S; Al-Saleh, Yousef; Wani, Kaiser; Alnaami, Abdullah M; Alfawaz, Hanan; Al-Ajlan, Abdulrahman S M; Kumar, Sudhesh; Chrousos, George P; Alokail, Majed S

2015-01-01

Non-high-density lipoprotein cholesterol (non-HDL-C) has been identified as a significant predictor of various cardiovascular events in adults. Limited studies have been conducted in the pediatric population with diverse results, depending on ethnic origin. None has been conducted in the Arabic adolescent population so far; this study aims to fill this gap. In this cross-sectional study, 1690 Saudi school adolescents (968 boys [mean age 14.8 ± 1.7] and 722 girls [mean age 14.6 ± 1.7]) were recruited. Anthropometrics were obtained. Fasting blood glucose and lipid profiles were quantified routinely. Non-HDL-C was calculated and screening was done for dyslipidemia using cutoffs obtained from the cohort and elevated fasting glucose. Using the 90th percentile cutoff obtained, the overall prevalence of high non-HDL-C (≥4.26 mmol/L) was 10.1%. Prevalence was slightly higher in girls (10.5%) than boys (9.9%). Non-HDL-C was similar to other lipids in terms of significant associations with anthropometric measures and glucose in both boys and girls. Elevated triglycerides was most predictive of elevated glucose in both girls (odds ratio 2.41; confidence interval 1.43-4.08; P = .001) and boys (odds ratio 2.61; confidence interval 1.70-4.0); P < .001). Non-HDL-C appears to be gender-specific and is cardiometabolically more associated with Saudi boys, despite higher levels in girls. It is inferior compared with triglycerides in assessing elevated glucose risk. Further investigations may provide a more definite value for non-HDL-C use as a biomarker in assessing cardiometabolic risk in the Arab adolescent population. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Elevated CO2 improves lipid accumulation by increasing carbon metabolism in Chlorella sorokiniana.

PubMed

Sun, Zhilan; Chen, Yi-Feng; Du, Jianchang

2016-02-01

Supplying microalgae with extra CO2 is a promising means for improving lipid production. The molecular mechanisms involved in lipid accumulation under conditions of elevated CO2, however, remain to be fully elucidated. To understand how elevated CO2 improves lipid production, we performed sequencing of Chlorella sorokiniana LS-2 cellular transcripts during growth and compared transcriptional dynamics of genes involved in carbon flow from CO2 to triacylglycerol. These analyses identified the majority genes of carbohydrate metabolism and lipid biosynthesis pathways in C. sorokiniana LS-2. Under high doses of CO2 , despite down-regulation of most de novo fatty acid biosynthesis genes, genes involved in carbohydrate metabolic pathways including carbon fixation, chloroplastic glycolysis, components of the pyruvate dehydrogenase complex (PDHC) and chloroplastic membrane transporters were upexpressed at the prolonged lipid accumulation phase. The data indicate that lipid production is largely independent of de novo fatty acid synthesis. Elevated CO2 might push cells to channel photosynthetic carbon precursors into fatty acid synthesis pathways, resulting in an increase of overall triacylglycerol generation. In support of this notion, genes involved in triacylglycerol biosynthesis were substantially up-regulated. Thus, elevated CO2 may influence regulatory dynamics and result in increased carbon flow to triacylglycerol, thereby providing a feasible approach to increase lipid production in microalgae. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

High Physical Activity is Associated with an Improved Lipid Profile and Resting Heart Rate among Healthy Middle-aged Chinese People.

PubMed

Hu, Bo; Liu, Xiao Yu; Zheng, Yao; Fan, Hong Min; Yin, Su Feng; Guo, Chun Yue; Li, Yun; Wu, Shou Ling; Feng, Fu Min; Yuan, Ju Xiang

2015-04-01

To investigate the effects of physical activity (PA) on dyslipidemia and elevated resting heart rate (RHR) in a large-scale cross-sectional study in China. We recruited community-based individuals who were 40-60 years old using a cluster sampling method. The PA levels of the participants were classified as low, moderate, or high, using the International Physical Activity Questionnaire. Dyslipidemia was defined as the detection of abnormalities in lipid indicators, and 4 lipid parameters were evaluated using fasting blood samples. Multivariate logistic regression analyses were used to evaluate the associations of PA with dyslipidemia and RHR. A total of 10,321 participants (38.88% men) were included in this study. The percentages of individuals with high, moderate, and low PA levels were 46.5%, 43.9%, and 9.6%, respectively. In both men and women, high PA provided odds ratios of 0.88 [95% confidence interval (CI): 0.83, 0.94] for dyslipidemia and 0.82 (95% CI: 0.73, 0.92) for elevated RHR, compared to participants with low PA. Our data suggested that substantial health benefits (related to dyslipidemia and elevated RHR) occurred at higher intensity PA, with greater energy consumption, in middle-aged Chinese people, and particularly in men. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Evaluation of lipid peroxidation and antioxidant status on fenvalerate, nitrate and their co-exposure in Bubalus bubalis.

PubMed

Gill, Kamalpreet Kaur; Sandhu, Harpal Singh; Kaur, Rajdeep

2015-09-01

The toxic effects of pesticides and minerals have been explored in different species, but still there is paucity of information regarding their combined toxicological effects. The present investigation reports oxidative stress induced by oral subacute exposure to fenvalerate (1 mg/kg) and sodium nitrate (20 mg/kg) alone, as well as in combination daily for 21 days in buffalo calves. Fenvalerate exposure produced significant elevation in lipid peroxidation (LPO), glutathione peroxidase (GPx), while it produced significant decline in blood glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT). No significant alteration was evidenced in nitric oxide (NOx) levels. Oral exposure to sodium nitrate produced significant inclination in LPO and NOx, while on the other hand significant depreciation in SOD and CAT with no significant change in GPx activity. Combined exposure to fenvalerate and sodium nitrate produced severe effects with an appreciably more prominent elevation in extent of LPO and decline in blood GSH levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Serum PCBs and organochlorine pesticides in Slovakia: age, gender, and residence as determinants of organochlorine concentrations.

PubMed

Petrik, Jan; Drobna, Beata; Pavuk, Marian; Jursa, Stanislav; Wimmerova, Sona; Chovancova, Jana

2006-10-01

We measured organochlorine concentrations of 15 polychlorinated biphenyl congeners and six organochlorine pesticides (PCB28, 52, 101, 123(+149), 118, 114, 153, 105, 138(+163), 167, 156(+171), 157, 180, 170, 189, alpha-, beta-, gamma-HCH, HCB, p,p'-DDT and p,p'-DDE) in 2047 subjects from contaminated and background areas of eastern Slovakia. Data were collected in 2001 and analyzed by high-resolution gas chromatography with electron capture detection in 2002-2003. Elevated levels persist in subjects from Michalovce district, site of former production facility, after almost 20-years since the end of the PCB manufacturing. Sum of 15 PCB congeners was 3105 ng/g of lipid in the Michalovce district versus 871 ng/g of lipid for subjects from the background districts of Svidnik and Stropkov. Relatively high concentration in children from the Michalovce district, sum PCB = 766 ng/g of lipid versus 372 ng/g of lipid in children from background area suggest ongoing exposure from environmental reservoirs and contaminated food. Consistent differences between genders in both contaminated and background areas are reported here. Levels in males are about 20% higher in both districts. Levels of organochlorine pesticides, particularly of DDT metabolite DDE and hexachlorobenzene are also elevated in the Michalovce district, reflecting intensive use of pesticides in agriculture in the past. About 30% decrease in serum organochlorine levels was observed in comparison with our earlier samples collected in 1998. These results suggest that contamination with PCBs still remains a source of relatively high environmental exposure for subjects in the Michalovce district.

Regulation of carbohydrate metabolism and flight performance by a hypertrehalosaemic hormone in the mosquito Anopheles gambiae

PubMed Central

Kaufmann, Christian; Brown, Mark R.

2008-01-01

The role of adipokinetic hormones (AKHs) in the regulation of carbohydrate and lipid metabolism and flight performance was evaluated for females of the African malaria mosquito, Anopheles gambiae. Injection of various dosages of synthetic Anoga-AKH-I increased carbohydrate levels in the haemolymph and reduced glycogen reserves in sugar-fed females but did not affect lipid levels. Anoga-AKH-I enhanced the flight performance of both intact and decapitated sugar-fed females, during a 4 hour flight period. Anoga-AKH-II had no effect on carbohydrate or lipid levels or flight performance, thus its function remains unknown. Targeted RNA-interference lowered Anoga-AKH receptor expression in sugar-fed females, consequently injections of Anoga-AKH-I failed to mobilize glycogen reserves. Taken together, these results show that a primary role for the neurohormone, Anoga-AKH-I, is to elevate trehalose levels in the haemolymph of female mosquitoes. PMID:18062987

Imiquimod induced ApoE-deficient mice might be a composite animal model for the study of psoriasis and dyslipideamia comorbidity.

PubMed

Xie, Xinran; Zhang, Lei; Lin, Yan; Wang, Yan; Liu, Weihong; Li, Xue; Li, Ping

2017-10-01

Psoriasis patients are at increased risk of developing lipid metabolism disturbances. Both psoriasis and dyslipideamia not only closely interact in disease development, but occur as mutual side effects in some medicine treatment. The interactive mechanism of the two diseases is complicated and still unclear. Here, we proposed applying imiquimod on the dorsal skin of ApoE -/- mice to establish a composite animal model which formed psoriasiform skin lesions under hyperlipidemic condition. By comparison with corresponding wild-type(C57BL/6) mice, the composite mice model was evaluated by skin pathological features, lipid levels, immune inflammatory factors in order to clarify the diseases interplay mechanism. In addition, IL-17 mAb treatment was applied to observe the effect of IL-17 antibody on the composite animal model. The results verified that imiquimod-induced ApoE -/- mice model presented keratinocyte hyperplasia, parakeratosis, inflammatory cells infiltration and elevated serum lipid levels, and also reflected the complex interaction between inflammation and lipid metabolism. IL-17 mAb could inhibit psoriasis skin lesions with lipid accumulation via STAT3 pathway, but no influence on elevated serum cholesterol. Imiquimod-induced ApoE -/- mice model presented the pathological features of psoriasis and dyslipideamia, which could be an ideal composite animal model for the study of pathogenesis and pharmacotherapeutics of psoriasis and dyslipideamia comorbidity. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Circulating levels of cholecystokinin and gastrin-releasing peptide in rainbow trout fed different diets.

PubMed

Jönsson, Elisabeth; Forsman, Antti; Einarsdottir, Ingibjörg E; Egnér, Barbro; Ruohonen, Kari; Björnsson, Björn Thrandur

2006-09-01

Cholecystokinin (CCK) and gastrin-releasing peptide (GRP) are gastrointestinal peptides thought to be important regulators of intake and digestion of food in vertebrates. In this study, pre- and postprandial plasma levels of CCK and GRP were measured in rainbow trout (Oncorhynchus mykiss) by the establishment of homologous radioimmunoassays, and the hormonal levels assessed in relation to dietary lipid:protein ratio and food intake. Fish were acclimated to either a high protein/low lipid diet (HP/LL diet; 14.1% lipids) or a normal protein/high lipid diet (NP/HL diet; 31.4% lipids). On three consecutive sampling days, radio-dense lead-glass beads were included in the diets for assessment of feed intake. Fish were terminally sampled for blood and stomach contents prior to feeding at time 0, and at 0.3, 1, 2, 4, 6, and 24 h after feeding. There was a postprandial elevation of plasma CCK levels, which was most evident after 4 and 6 h. Fish fed the NP/HL diet had higher plasma CCK levels compared with those fed the HP/LL diet. Plasma CCK levels were not affected by the amount of food ingested. GRP levels in plasma were not influenced by sampling time, diet, or feed intake. The results indicate that the endocrine release of gastrointestinal CCK is increased during feeding and may be further influenced by the dietary lipid:protein ratio in rainbow trout. Plasma GRP levels, on the other hand, appear not to be influenced by feeding or diet composition.

Mild subclinical hypothyroidism is associated with paediatric dyslipidaemia.

PubMed

Dahl, Amanda R; Iqbal, Anoop Mohamed; Lteif, Aida N; Pittock, Siobhan T; Tebben, Peter J; Kumar, Seema

2018-05-30

There is a lack of consensus on the cardiometabolic consequences of mild subclinical hypothyroidism (SCH) among children. The objective of the current study was to compare lipid profiles in children with mild SCH with those of euthyroid children. Retrospective medical record review. Children (ages 2-18 years) who had undergone simultaneous measurement of TSH, free thyroxine (T4) and lipids. Lipids in children with mild SCH (TSH 5-<10 mIU/L and normal free T4, n = 228) were compared with those in euthyroid children (n = 1215). TSH level was positively associated with total cholesterol and nonhigh density lipoprotein (non-HDL) cholesterol [β 0.05(0.03-0.08), P < .0001 and β 0.05(0.03-0.08), P < .0001, respectively]. Total cholesterol was significantly higher in children and adolescents with mild SCH compared with euthyroid children (4.43 ± 1.14 mmol/L vs 4.2 ± 0.85 mmol/L, P = .0005). Similarly, non-HDL cholesterol level was also higher in children with mild SCH relative to euthyroid children (3.08 ± 1.14 mmol/L vs 2.91 ± 0.8 mmol/L, P = .001). The adjusted odds ratio of having elevated total cholesterol and elevated non-HDL cholesterol was greater in children with mild SCH compared with euthyroid children (OR 1.88, 95% CI; 1.28-2.73; P = .001 and 1.72, 95% CI 1.2-2.5; P = .003, respectively). The presence of thyroid autoimmunity was not associated with higher rates of dyslipidaemia. Mild SCH in children and adolescents was associated with higher rates of elevated total cholesterol and elevated non-HDL cholesterol. Randomized placebo controlled studies are warranted to determine if treatment of mild SCH in children leads to improvement in lipid profile. © 2018 John Wiley & Sons Ltd.

Fasting time and lipid parameters: association with hepatic steatosis — data from a random population sample

PubMed Central

2014-01-01

Background Current guidelines recommend measuring plasma lipids in fasting patients. Recent studies, however, suggest that variation in plasma lipid concentrations secondary to fasting time may be minimal. Objective of the present study was to investigate the impact of fasting time on plasma lipid concentrations (total cholesterol, HDL and LDL cholesterol, triglycerides). A second objective was to determine the effect of non-alcoholic fatty liver disease exerted on the above-mentioned lipid levels. Method Subjects participating in a population-based cross-sectional study (2,445 subjects; 51.7% females) were questioned at time of phlebotomy regarding duration of pre-phlebotomy fasting. Total cholesterol, LDL and HDL cholesterol, and triglycerides were determined and correlated with length of fasting. An upper abdominal ultrasonographic examination was performed and body-mass index (BMI) and waist-to-hip ratio (WHR) were calculated. Subjects were divided into three groups based on their reported fasting periods of 1–4 h, 4–8 h and > 8 h. After application of the exclusion criteria, a total of 1,195 subjects (52.4% females) were included in the study collective. The Kruskal-Wallis test was used for continuous variables and the chi-square test for categorical variables. The effects of age, BMI, WHR, alcohol consumption, fasting time and hepatic steatosis on the respective lipid variables were analyzed using multivariate logistic regression. Results At multivariate analysis, fasting time was associated with elevated triglycerides (p = 0.0047 for 1–4 h and p = 0.0147 for 4–8 h among females; p < 0.0001 for 1–4 h and p = 0.0002 for 4–8 h among males) and reduced LDL cholesterol levels (p = 0.0003 for 1–4 h and p = 0.0327 for 4–8 h among males). Among males, hepatic steatosis represents an independent factor affecting elevated total cholesterol (p = 0.0278) and triglyceride concentrations (p = 0.0002). Conclusion Total and HDL cholesterol concentrations are subject to slight variations in relation to the duration of the pre-phlebotomy fasting period. LDL cholesterol and triglycerides exhibit highly significant variability; the greatest impact is seen with the triglycerides. Fasting time represents an independent factor for reduced LDL cholesterol and elevated triglyceride concentrations. There is a close association between elevated lipids and hepatic steatosis. PMID:24447492

Transcriptome profiling identifies p53 as a key player during calreticulin deficiency: Implications in lipid accumulation.

PubMed

Vig, Saurabh; Talwar, Puneet; Kaur, Kirandeep; Srivastava, Rohit; Srivastava, Arvind K; Datta, Malabika

2015-01-01

Calreticulin (CRT) is an endoplasmic reticulum (ER) resident calcium binding protein that is involved in several cellular activities. Transcriptome analyses in CRT knockdown HepG2 cells revealed 253 altered unique genes and subsequent in silico protein-protein interaction network and MCODE clustering identified 34 significant clusters, of which p53 occupied the central hub node in the highest node-rich cluster. Toward validation, we show that CRT knockdown leads to inhibition of p53 protein levels. Both, CRT and p53 siRNA promote hepatic lipid accumulation and this was accompanied by elevated SREBP-1c and FAS levels. p53 was identified to bind at -219 bp on the SREBP-1c promoter and in the presence of CRT siRNA, there was decreased occupancy of p53 on this binding element. This was associated with increased SREBP-1c promoter activity and both, mutation in this binding site or p53 over-expression antagonised the effects of CRT knockdown. We, therefore, identify a negatively regulating p53 binding site on the SREBP-1c promoter that is critical during hepatic lipid accumulation. These results were validated in mouse primary hepatocytes and toward a physiological relevance, we report that while the levels of CRT and p53 are reduced in the fatty livers of diabetic db/db mice, SREBP-1c levels are significantly elevated. Our results suggest that decreased CRT levels might be involved in the development of a fatty liver by preventing p53 occupancy on the SREBP-1c promoter and thereby facilitating SREBP-1c up-regulation and consequently, lipid accumulation.

Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors.

PubMed

Pereira, Maria J; Skrtic, Stanko; Katsogiannos, Petros; Abrahamsson, Niclas; Sidibeh, Cherno O; Dahgam, Santosh; Månsson, Marianne; Risérus, Ulf; Kullberg, Joel; Eriksson, Jan W

2016-12-01

Elevated levels of circulating non-esterified fatty acids (NEFA) mediate many adverse metabolic effects. In this work we aim to determine the impact of type 2 diabetes (T2D), glycemic control and obesity on lipolysis regulation. 20 control and 20 metformin-treated T2D subjects were matched for sex (10M/10 F), age (58±11 vs 58±9 y) and BMI (30.8±4.6 vs 30.7±4.9kg/m 2 ). In vivo lipolysis was assessed during a 3h-OGTT with plasma glycerol and NEFA levels. Subcutaneous adipose tissue (SAT) biopsies were obtained to measure mRNA and metabolite levels of factors related to lipolysis and lipid storage and to assess in vitro lipolysis in isolated subcutaneous adipocytes. Plasma NEFA AUC during the OGTT where higher 30% (P=0.005) in T2D than in control subjects, but plasma glycerol AUC and subcutaneous adipocyte lipolysis in vitro were similar, suggesting that adipose tissue lipolysis is not altered. Expression in SAT of genes involved in lipid storage (FABP4, DGAT1, FASN) were reduced in T2D subjects compared with controls, but no differences were seen for genes involved in lipolysis. T2D subjects had elevated markers of beta-oxidation, α-hydroxybutyrate (1.4-fold, P<0.01) and β-hydroxybutyrate (1.7-fold, P<0.05) in plasma. In multivariate analysis, HbA1c, visceral adipose tissue volume and sex (male) were significantly associated with NEFA AUC in T2D subjects. In T2D subjects, NEFA turnover is impaired, but not due to defects in lipolysis or lipid beta-oxidation. Impaired adipose NEFA re-esterification or de novo lipogenesis is likely to contribute to higher NEFA plasma levels in T2D. The data suggest that hyperglycemia and adiposity are important contributing factors for the regulation of plasma NEFA concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

Homocysteine regulates fatty acid and lipid metabolism in yeast.

PubMed

Visram, Myriam; Radulovic, Maja; Steiner, Sabine; Malanovic, Nermina; Eichmann, Thomas O; Wolinski, Heimo; Rechberger, Gerald N; Tehlivets, Oksana

2018-04-13

S -Adenosyl-l-homocysteine hydrolase (AdoHcy hydrolase; Sah1 in yeast/AHCY in mammals) degrades AdoHcy, a by-product and strong product inhibitor of S -adenosyl-l-methionine (AdoMet)-dependent methylation reactions, to adenosine and homocysteine (Hcy). This reaction is reversible, so any elevation of Hcy levels, such as in hyperhomocysteinemia (HHcy), drives the formation of AdoHcy, with detrimental consequences for cellular methylation reactions. HHcy, a pathological condition linked to cardiovascular and neurological disorders, as well as fatty liver among others, is associated with a deregulation of lipid metabolism. Here, we developed a yeast model of HHcy to identify mechanisms that dysregulate lipid metabolism. Hcy supplementation to wildtype cells up-regulated cellular fatty acid and triacylglycerol content and induced a shift in fatty acid composition, similar to changes observed in mutants lacking Sah1. Expression of the irreversible bacterial pathway for AdoHcy degradation in yeast allowed us to dissect the impact of AdoHcy accumulation on lipid metabolism from the impact of elevated Hcy. Expression of this pathway fully suppressed the growth deficit of sah1 mutants as well as the deregulation of lipid metabolism in both the sah1 mutant and Hcy-exposed wildtype, showing that AdoHcy accumulation mediates the deregulation of lipid metabolism in response to elevated Hcy in yeast. Furthermore, Hcy supplementation in yeast led to increased resistance to cerulenin, an inhibitor of fatty acid synthase, as well as to a concomitant decline of condensing enzymes involved in very long-chain fatty acid synthesis, in line with the observed shift in fatty acid content and composition. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

European Consensus on Primary Prevention of Coronary Heart Disease.

PubMed

Assmann, G

1988-07-01

The European Consensus on Primary Prevention of Coronary Heart Disease has recommended that providing care for individuals at particular risk for coronary artery disease (CAD) requires case finding through medical examinations in primary care, hospital and employment health examination settings. Decisions concerning management of elevated lipid levels should be based on overall cardiovascular risk. The goal of reducing cholesterol levels through risk reduction can ultimately be accomplished only with the implementation of health education efforts directed toward all age groups and actions by government and supranational agencies, including adequate food labelling to identify fat content, selective taxation to encourage healthful habits and wider availability of exercise facilities. Only measures directed at the overall population can eventually reach the large proportion of individuals at mildly to moderately increased risk for CAD. The European Policy Statement on the Prevention of Coronary Heart Disease recognizes that the question of lipid elevation as a risk factor for CAD involves assessment, not only of cholesterol level alone, but also of triglycerides and the HDL cholesterol lipid fraction. Five specific categories of dyslipidemia have been identified, with individualized screening and treatment strategies advised for each. It is the consensus of the study group panel members that these procedures are both practical and feasible. They begin the necessary long term process to reduce the unacceptably high levels of morbidity and mortality due to CAD throughout the European community.

Elevated levels of triglyceride and triglyceride-rich lipoprotein triglyceride induced by a high-carbohydrate diet is associated with polymorphisms of APOA5-1131T>C and APOC3-482C>T in Chinese healthy young adults.

PubMed

Lin, Jia; Fang, Ding Zhi; Du, Juan; Shigdar, Sarah; Xiao, Li Ying; Zhou, Xue Dong; Duan, Wei

2011-01-01

Changes in lipid profiles have been shown to be associated with diet and apolipoprotein (APO) polymorphisms. Therefore, 2 polymorphisms, i.e. APOA5-1131T>C and APOC3-482C>T, and serum lipids were examined in a Chinese healthy young population with high-carbohydrate/low-fat (HC/LF) diet intervention. After a wash-out diet for 7 days, 56 young adults (22.89 ± 1.80 years) received the HC/LF diet for 6 days. Body mass index (BMI) and fasting serum lipid profiles at baseline, after the wash-out diet, and after the HC/LF diet were measured. APOA5-1131C carriers had higher triglyceride (TG) and TG-rich lipoprotein TG (TRL-TG) levels at baseline and after the HC/LF diet, though this mainly corresponded to the female cohort. APOC3-482T carriers had higher TRL-TG levels following the wash-out and HC/LF diets, but these were not directly attributable to a single gender. Both polymorphisms may play an important role in the elevated TG and TRL-TG levels induced by the HC/LF diet, especially in females, thus indicating a potential dietary prevention of coronary heart disease in this Chinese cohort. Copyright © 2011 S. Karger AG, Basel.

Dentate gyrus-cornu ammonis (CA) 4 volume is decreased and associated with depressive episodes and lipid peroxidation in bipolar II disorder: Longitudinal and cross-sectional analyses.

PubMed

Elvsåshagen, Torbjørn; Zuzarte, Pedro; Westlye, Lars T; Bøen, Erlend; Josefsen, Dag; Boye, Birgitte; Hol, Per K; Malt, Ulrik F; Young, L Trevor; Andreazza, Ana C

2016-12-01

Reduced dentate gyrus volume and increased oxidative stress have emerged as potential pathophysiological mechanisms in bipolar disorder. However, the relationship between dentate gyrus volume and peripheral oxidative stress markers remains unknown. Here, we examined dentate gyrus-cornu ammonis (CA) 4 volume longitudinally in patients with bipolar II disorder (BD-II) and healthy controls and investigated whether BD-II is associated with elevated peripheral levels of oxidative stress. We acquired high-resolution structural 3T-magnetic resonance imaging (MRI) images and quantified hippocampal subfield volumes using an automated segmentation algorithm in individuals with BD-II (n=29) and controls (n=33). The participants were scanned twice, at study inclusion and on average 2.4 years later. In addition, we measured peripheral levels of two lipid peroxidation markers (4-hydroxy-2-nonenal [4-HNE] and lipid hydroperoxides [LPH]). First, we demonstrated that the automated hippocampal subfield segmentation technique employed in this work reliably measured dentate gyrus-CA4 volume. Second, we found a decreased left dentate gyrus-CA4 volume in patients and that a larger number of depressive episodes between T1 and T2 predicted greater volume decline. Finally, we showed that 4-HNE was elevated in BD-II and that 4-HNE was negatively associated with left and right dentate gyrus-CA4 volumes in patients. These results are consistent with a role for the dentate gyrus in the pathophysiology of bipolar disorder and suggest that depressive episodes and elevated oxidative stress might contribute to hippocampal volume decreases. In addition, these findings provide further support for the hypothesis that peripheral lipid peroxidation markers may reflect brain alterations in bipolar disorders. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of thyroid function on LDL oxidation.

PubMed

Costantini, F; Pierdomenico, S D; De Cesare, D; De Remigis, P; Bucciarelli, T; Bittolo-Bon, G; Cazzolato, G; Nubile, G; Guagnano, M T; Sensi, S; Cuccurullo, F; Mezzetti, A

1998-05-01

In this study, the effect of different levels of thyroid hormone and metabolic activity on low density lipoprotein (LDL) oxidation was investigated. Thus, in 16 patients with hyperthyroidism, 16 with hypothyroidism, and 16 age- and sex-matched healthy normolipidemic control subjects, the native LDL content in lipid peroxides, vitamin E, beta-carotene, and lycopene, as well as the susceptibility of these particles to undergo lipid peroxidation, was assessed. Hyperthyroidism was associated with significantly higher lipid peroxidation, as characterized by a higher native LDL content in lipid peroxides, a lower lag phase, and a higher oxidation rate than in the other two groups. This elevated lipid peroxidation was associated with a lower LDL antioxidant concentration. Interestingly, hypothyroid patients showed an intermediate behavior. In fact, in hypothyroidism, LDL oxidation was significantly lower than in hyperthyroidism but higher than in the control group. Hypothyroidism was also characterized by the highest beta-carotene LDL content, whereas vitamin E was significantly lower than in control subjects. In hyperthyroidism but not in the other two groups, LDL oxidation was strongly influenced by free thyroxine blood content. In fact in this group, the native LDL lipid peroxide content and the lag phase were directly and indirectly, respectively, related to free thyroxine blood levels. On the contrary, in hypothyroidism LDL oxidation was strongly and significantly related to serum lipids. In conclusion, both hypothyroidism and hyperthyroidism are characterized by higher levels of LDL oxidation when compared with normolipidemic control subjects. In hyperthyroid patients, the increased lipid peroxidation was strictly related to free thyroxine levels, whereas in hypothyroidism it was strongly influenced by serum lipids.

Volunteering and Cardiovascular Disease Risk: Does Helping Others Get "Under the Skin?".

PubMed

Burr, Jeffrey A; Han, Sae Hwang; Tavares, Jane L

2016-10-01

This study investigated whether volunteering was related to 5 risk factors for cardiovascular disease (CVD) and the metabolic syndrome (MetS) among middle-aged and older adults. Data from the 2004 and 2006 waves of the Health and Retirement Study (N = 7,803) were examined. Logistic regression was used to describe the relationships among volunteering and central adiposity, hypertension, lipid dysregulation, elevated blood glucose levels, and high inflammation, along with 2 indexes of the MetS. Among middle-aged adults, results showed that volunteers were less likely to have high central adiposity, lipid dysregulation, elevated blood glucose levels, and MetS compared with non-volunteers. For older adults, results showed volunteers were less likely to be hypertensive and more likely to have lipid dysregulation than their non-volunteer counterparts. These results supported findings from other studies that formal volunteering is beneficial for middle-aged adults, and to a lesser degree, older adults. Further research is required to determine what factors may mediate the volunteer-CVD risk relationships. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

α-lipoic acid ameliorates n-3 highly-unsaturated fatty acids induced lipid peroxidation via regulating antioxidant defenses in grass carp (Ctenopharyngodon idellus).

PubMed

Shi, Xiao-Chen; Jin, Ai; Sun, Jian; Yang, Zhou; Tian, Jing-Jing; Ji, Hong; Yu, Hai-Bo; Li, Yang; Zhou, Ji-Shu; Du, Zhen-Yu; Chen, Li-Qiao

2017-08-01

This study evaluated the protective effect of α-lipoic acid (LA) on n-3 highly unsaturated fatty acids (HUFAs)-induced lipid peroxidation in grass carp. The result indicated that diets with n-3 HUFAs increased the production of malondialdehyde (MDA) (P < 0.05), thereby inducing lipid peroxidation in liver and muscle of grass carp. Meanwhile, compared with control group, the hepatosomatic index (HSI) and kidney index (KI) of grass carp were markedly increased in n-3 HUFAs-only group. However, diets with LA remarkably inhibited the n-3 HUFAs-induced increase of HSI, KI, and MDA level in serum, liver and muscle (P < 0.05). Interestingly, LA also significantly elevated the ratio of total n-3 HUFAs in fatty acid composition of muscle and liver (P < 0.05). Furthermore, LA significantly promoted the activity of antioxidant enzymes in serum, muscle and liver of grass carp (P < 0.05), including superoxide dismutase (SOD), catalase (CAT), and glutathione s-transferase (GST). The further results showed that LA significantly elevated mRNA expression of antioxidant enzymes with promoting the mRNA expression of NF-E2-related nuclear factor 2 (Nrf2) and decreasing Kelch-like-ECH-associated protein 1 (Keap1) mRNA level. From the above, these results suggested that LA could attenuate n-3 HUFAs-induced lipid peroxidation, remit the toxicity of the lipid peroxidant, and protect n-3 HUFAs against lipid peroxidation to promote its deposition in fish, likely strengthening the activity of antioxidant enzymes through regulating mRNA expressions of antioxidant enzyme genes via mediating Nrf2-Keap1 signaling pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

Vitamin E Protects against Lipid Peroxidation and Rescues Tumorigenic Phenotypes in Cowden/Cowden-like Patient-derived Lymphoblast Cells with Germline SDHx Variants

PubMed Central

Ni, Ying; Eng, Charis

2012-01-01

Purpose Cowden syndrome (CS), a Mendelian autosomal-dominant disorder, predisposes to breast, thyroid, and other cancers. Germline variations in succinate dehydrogenase genes (SDHx) occur in ~10% PTEN mutation-negative CS and CS-like (CSL) individuals (SDHvar+). We previously showed that SDHx variants result in elevated reactive oxygen species (ROS), disruption of nicotinamide adenine dinucleotide (NAD) equilibrium, and destabilization of p53 hence apoptosis resistance in CS/CSL patient-derived lymphoblastoid cells. In the present study, we sought to address the tumorigenic impacts of increased ROS and the potential of protecting SDHvar+ cells with antioxidants. Experimental Design We measured the lipid peroxidation levels in patient-derived SDHvar+ lymphoblastoid cells and sequenced 74 controls or SDHvar+ germline DNA samples for mitochondrial hypervariable region II (HVRII) polymorphisms. SDHvar+ lymphoblastoid cells were treated with various antioxidants to check p53 expression and SubG1 cell population with cell cycle analysis. Results We demonstrated that elevated ROS results in higher lipid peroxidation in SDHvar+ cells. Accumulation of polymorphisms in mitochondrial HVRII were observed in SDHvar+ samples. Interestingly, α-tocopherol (vitamin E) treatment, but not other antioxidants, rescued SDHvar+ cells from apoptosis resistance and protected SDHvar+ cells from oxidative damage such as decreased lipid peroxidation as well as partially recovered p53 expression and NAD/NADH levels. Conclusions We conclude that disruption of complex II due to SDHx variants leads to increased ROS generation, specifically accompanied by lipid peroxidation. The lipid soluble antioxidant α-tocopherol can selectively protect SDHxvar+ cells from oxidative damage, apoptosis resistance, and rebalance redox metabolites NAD/NADH. PMID:22829200

Association of Lipid Fractions With Risks for Coronary Artery Disease and Diabetes.

PubMed

White, Jon; Swerdlow, Daniel I; Preiss, David; Fairhurst-Hunter, Zammy; Keating, Brendan J; Asselbergs, Folkert W; Sattar, Naveed; Humphries, Steve E; Hingorani, Aroon D; Holmes, Michael V

2016-09-01

Low-density lipoprotein cholesterol (LDL-C) is causally related to coronary artery disease (CAD), but the relevance of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) is uncertain. Lowering of LDL-C levels by statin therapy modestly increases the risk of type 2 diabetes, but it is unknown whether this effect is specific to statins. To investigate the associations of 3 routinely measured lipid fractions with CAD and diabetes through mendelian randomization (MR) using conventional MR and making use of newer approaches, such as multivariate MR and MR-Egger, that address the pleiotropy of genetic instruments where relevant. Published data from genome-wide association studies were used to construct genetic instruments and then applied to investigate associations between lipid fractions and the risk of CAD and diabetes using MR approaches that took into account pleiotropy of genetic instruments. The study was conducted from March 12 to December 31, 2015. Coronary artery disease and diabetes. Genetic instruments composed of 130 single-nucleotide polymorphisms (SNPs) were used for LDL-C (explaining 7.9% of its variance), 140 SNPs for HDL-C (6.6% of variance), and 140 SNPs for TGs (5.9% of variance). A 1-SD genetically instrumented elevation in LDL-C levels (equivalent to 38 mg/dL) and TG levels (equivalent to 89 mg/dL) was associated with higher CAD risk; odds ratios (ORs) were 1.68 (95% CI, 1.51-1.87) for LDL-C and 1.28 (95% CI, 1.13-1.45) for TGs. The corresponding OR for HDL-C (equivalent to a 16-mg/dL increase) was 0.95 (95% CI, 0.85-1.06). All 3 lipid traits were associated with a lower risk of type 2 diabetes. The ORs were 0.79 (95% CI, 0.71-0.88) for LDL-C and 0.83 (95% CI, 0.76-0.90) for HDL-C per 1-SD elevation. For TG, the MR estimates for diabetes were inconsistent, with MR-Egger giving an OR of 0.83 (95%CI, 0.72-0.95) per 1-SD elevation. Routinely measured lipid fractions exhibit contrasting associations with the risk of CAD and diabetes. Increased LDL-C, HDL-C, and possibly TG levels are associated with a lower risk of diabetes. This information will be relevant to the design of clinical trials of lipid-modifying agents, which should carefully monitor participants for dysglycemia and the incidence of diabetes.

Cardiac fatty acid uptake and metabolism in the rat model of polycystic ovary syndrome.

PubMed

Tepavčević, Snežana; Milutinović, Danijela Vojnović; Macut, Djuro; Stojiljković, Mojca; Nikolić, Marina; Božić-Antić, Ivana; Ćulafić, Tijana; Bjekić-Macut, Jelica; Matić, Gordana; Korićanac, Goran

2015-09-01

Polycystic ovary syndrome (PCOS) is associated with an altered plasma lipid profile and increased risk for cardiovascular diseases. We hypothesized that molecular mechanisms underlying cardiac pathology in PCOS involve changes in expression and subcellular localization of several key proteins involved in cardiac lipid transport and metabolism, such as fatty acid transporter CD36, lipin 1, peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ coactivator-1 (PGC1), and carnitine palmitoyltransferase 1 (CPT1). We used the animal model of PCOS obtained by treating female rats with dihydrotestosterone (DHT). Protein levels of CD36, lipin 1, PPARα, PGC1, and antioxidative enzymes were assessed by Western blot in different cardiac cell compartments. Cardiac triglycerides (TG) and lipid peroxidation were also measured. The content of CD36 was decreased in both the cardiac plasma membranes and intracellular pool. On the other hand, total content of cardiac lipin 1 in DHT-treated rats was elevated, in contrast to decreased microsomal lipin 1 content. An increase in nuclear content of lipin 1 was observed together with elevation of nuclear PPARα and PGC1, and an increase in CPT1 expression. However, lipid peroxidation was reduced in the heart, without alterations in antioxidative enzymes expression and cardiac TG content. The results indicate that treatment of female rats with DHT is accompanied by a decrease of fatty acid uptake and a reduction of lipid peroxidation in the heart. The observed elevation of lipin 1, PPARα, PGC1, and CPT1 expression suggests that cardiac fatty acid metabolism is shifted toward mitochondrial beta oxidation.

Evaluation of serum lipid profile, body mass index, and waistline in Chinese patients with type 2 diabetes mellitus.

PubMed

Cui, Rongtao; Qi, Zhiming; Zhou, Lin; Li, Zuohong; Li, Qing; Zhang, Junyong

2016-01-01

People with type 2 diabetes are at an increased risk of hypertension, arteriosclerosis, heart disease, and stroke. Glucose intolerance (insulin resistance) is the main feature of type 2 diabetes. Obesity leads to insulin resistance, dyslipidemia, etc. The aim of this study was to assess the biochemical parameters and measures of obesity in type 2 diabetes mellitus (T2DM). A total of 2,273 males and 6,547 females previously healthy volunteers (aged 41-95 years old) were recruited by open invitation. The basic information, including age, sex, height, weight, body mass index (BMI), waistline, hipline, menstrual cycle, and medical history, was collected by questionnaire survey and physical examination. Serum lipid profile, liver transaminase, blood glucose, postprandial blood glucose, and hemoglobin A1c were obtained after 12 hours of fasting. According to our results, diabetic patients presented serum lipid abnormality. Elevated triglyceride (TG) levels (≥1.7 mmol/L) were noted in 19.69% of males and 20.40% of females, and reduced high-density lipoprotein cholesterol (HDL-C) levels (≤1.15 mmol/L) were noted in 21.96% of males and 15.74% of females. The combination of elevated TG and reduced HDL-C was the most prevalent of the combined lipid abnormalities. In contrast, no differences were observed in the levels of low-density lipoprotein cholesterol and total cholesterol. Moreover, there were statistically significant differences in the levels of BMI and waistline between T2DM and non-T2DM participants. After adjustment for BMI, logistic regression analysis revealed that the subjects with BMI ≤20 kg/m(2) and >30 kg/m(2) had a significantly elevated hazard ratio of T2DM compared with participants having a BMI range of 20-30 kg/m(2) in both males and females. However, there was a significant difference between T2DM patients and non-T2DM patients in waistline (χ (2)=8.57, P<0.001) than in BMI parameter (χ (2)=6.29, P<0.001). The present study shows for the first time that low levels of HDL-C, high levels of TG, and abnormal levels in BMI and waistline increase the risk of type 2 T2DM in Chinese people.

Assessment of high-sensitivity C-reactive protein and lipid levels in healthy adults and patients with coronary artery disease, with and without periodontitis--a cross-sectional study.

PubMed

Kumar, K R V; Ranganath, V; Naik, R; Banu, S; Nichani, A S

2014-12-01

Various epidemiological studies have implied that local infection may increase the levels of systemic inflammatory mediators and lipid mediators, thereby promoting atherosclerosis. The aim of this study was to assess high-sensitivity C-reactive protein (HsCRP) and lipid levels in healthy adults and patients with coronary artery disease (CAD), with and without periodontitis. A total of 100 subjects were included in the study and categorized into four groups of 25 subjects each, as follows: subjects with chronic periodontitis with angiographically proven CAD; nonperiodontitis subjects with angiographically proven CAD; otherwise healthy subjects with only chronic periodontitis; and systemically and orally healthy individuals. The periodontal parameters measured included plaque index, gingival index, probing pocket depth, clinical attachment level and marginal alveolar bone loss (which was recorded radiographically). Serum samples were collected for estimation of HsCRP, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglycerides (TGs). The serum HsCRP levels in subjects with either CAD or chronic periodontitis were elevated two-fold compared with those of healthy individuals, whereas in subjects with both diseases (CAD plus chronic periodontitis) the levels were elevated three-fold. The serum LDL level was higher, and the serum HDL level was lower, in all the test groups compared with the healthy group. No significant difference among the groups was detected in the TG levels. A persistent infection, such as chronic periodontitis, may influence changes in the systemic levels of HsCRP, LDL and HDL, which potentially have an impact on inflammation-associated atherosclerotic processes, such as CAD. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer's disease.

PubMed

Chia, L S; Thompson, J E; Moscarello, M A

1984-09-05

Wide-angle X-ray diffraction studies revealed that the lipid phase transition temperature of myelin from brain tissue of humans with Alzheimer's disease was about 12 degrees C lower than that of normal age-matched controls, indicating differences in the physical organization of the myelin lipid bilayer. Elevated levels of malondialdehyde and conjugated diene were found in brain tissue from humans with Alzheimer's disease, indicating an increased amount of lipid peroxidation over the controls. An increase in myelin disorder and in lipid peroxidation can both be correlated with aging in human brain, but the changes in myelin from humans with Alzheimer's disease are more pronounced than in normal aging. These changes might represent severe or accelerated aging.

Elevated blood lipids are uncommon in patients with post-polio syndrome--a cross sectional study.

PubMed

Melin, Eva; Kahan, Thomas; Borg, Kristian

2015-04-29

The post-polio syndrome occurs in people who previously have had poliomyelitis. After the initial recovery, new or increasing neurologic symptoms occur. Inflammation and dyslipidaemia may play an important role in the development of atherosclerotic complications, for example myocardial infarction and angina pectoris. Previous studies on cardiovascular risk factors in the post-polio syndrome have found a higher prevalence of hypertension, ischemic heart disease, hyperlipidaemia, and stroke in these patients. The present study was undertaken in order to evaluate whether post-polio patients have elevated lipid values, and if blood lipid abnormalities could be correlated to signs of inflammation. Cross-sectional study of 89 consecutive post-polio patients, (53 women, mean age 65 years) from the Post-Polio Outpatient Clinic, Danderyd University Hospital, Stockholm, Sweden. The lipid profiles of post-polio patients were compared to age and sex matched reference values from two earlier studies. Statistical analyses were performed by the Student's t-test, and linear regression analyses were assessed by Pearson's correlation coefficient. Mean total cholesterol levels (5.7 mmol/L) were low or normal in post-polio patients, whereas low density lipoprotein levels (3.6 mmol/L) were normal, and high density lipoprotein (1.5 mmol/L) and triglycerides (1.4 mmol/L) lower than reference values. The prevalence of diabetes (7%), hypertension (38%), concomitant cardiovascular disease, (including angina pectoris, myocardial infarction, heart failure, atrial fibrillation and stroke) (7%), and calculated 10 year risk of coronary heart disease according to Framingham risk score algorithm (8%) was not increased in post-polio patients. Compared to reference populations, post-polio patients in Sweden appear to have low or normal total cholesterol and low density lipoprotein levels, whereas high density lipoprotein and triglyceride levels are low. Hence, a possible persisting inflammatory process in post-polio syndrome does not seem to be associated with increased lipids and an increased risk for coronary heart disease events.

Tris(1,3-dichloro-2-propyl) phosphate perturbs the expression of genes involved in immune response and lipid and steroid metabolism in chicken embryos

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farhat, Amani; National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3; Buick, Julie K.

We previously demonstrated that in ovo exposure to the flame retardant tris(1,3-dichloro-2-propyl) phosphate (TDCPP) decreased plasma thyroxine levels, reduced growth parameters, and decreased gallbladder size in chicken embryos. In the current study DNA microarrays were used to evaluate global mRNA expression in liver tissue of male chicken embryos that exhibited the above mentioned effects. Injected doses were dimethyl sulfoxide vehicle control, 7.6 or 45 μg TDCPP/g egg. TDCPP caused significant changes in the expression of five genes at the low dose and 47 genes at the high dose (False Discovery Rate p ≤ 0.1, fold change ≥ 1.5). The genemore » expression analysis suggested a compromised immune function, a state of cholestatic liver/biliary fibrosis, and disrupted lipid and steroid metabolism. Circulating bile acid levels were elevated, which is an indication of liver dysfunction, and plasma cholesterol levels were reduced; however, hepatic bile acid and cholesterol levels were unaltered. Interactome analyses identified apolipoprotein E, hepatocyte nuclear factor 4 alpha, and peroxisome proliferator-activated receptor alpha as key regulatory molecules involved in the effects of TDCPP. Our results demonstrate a targeted effect of TDCPP toxicity on lipid metabolism, including cholesterol, that helps explain the aforementioned phenotypic effects, as chicken embryos are highly dependent on yolk lipids for growth and maintenance throughout development. Finally, our results are in concordance with the literature that describes TDCPP as a cancer-causing agent, since the majority of dysregulated genes were involved in cancer pathways. - Highlights: • TDCPP dysregulates genes involved in immune function and lipid metabolism. • A targeted effect of TDCPP toxicity on cholesterol metabolism is apparent. • A state of cholestatic liver fibrosis is suggested by the expression profile. • Elevated plasma bile acids suggest that TDCPP causes liver dysfunction.« less

Lower serum testosterone associated with elevated polychlorinated biphenyl concentrations in Native American men.

PubMed

Goncharov, Alexey; Rej, Robert; Negoita, Serban; Schymura, Maria; Santiago-Rivera, Azara; Morse, Gayle; Carpenter, David O

2009-09-01

Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05-0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06-0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men.

Elevated host lipid metabolism revealed by iTRAQ-based quantitative proteomic analysis of cerebrospinal fluid of tuberculous meningitis patients.

PubMed

Mu, Jun; Yang, Yongtao; Chen, Jin; Cheng, Ke; Li, Qi; Wei, Yongdong; Zhu, Dan; Shao, Weihua; Zheng, Peng; Xie, Peng

2015-10-30

Tuberculous meningitis (TBM) remains to be one of the most deadly infectious diseases. The pathogen interacts with the host immune system, the process of which is largely unknown. Various cellular processes of Mycobacterium tuberculosis (MTB) centers around lipid metabolism. To determine the lipid metabolism related proteins, a quantitative proteomic study was performed here to identify differential proteins in the cerebrospinal fluid (CSF) obtained from TBM patients (n = 12) and healthy controls (n = 12). CSF samples were desalted, concentrated, labelled with isobaric tags for relative and absolute quantitation (iTRAQ™), and analyzed by multi-dimensional liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene ontology and proteomic phenotyping analysis of the differential proteins were conducted using Database for Annotation, Visualization, and Integrated Discovery (DAVID) Bioinformatics Resources. ApoE and ApoB were selected for validation by ELISA. Proteomic phenotyping of the 4 differential proteins was invloved in the lipid metabolism. ELISA showed significantly increased ApoB levels in TBM subjects compared to healthy controls. Area under the receiver operating characteristic curve analysis demonstrated ApoB levels could distinguish TBM subjects from healthy controls and viral meningitis subjects with 89.3% sensitivity and 92% specificity. CSF lipid metabolism disregulation, especially elevated expression of ApoB, gives insights into the pathogenesis of TBM. Further evaluation of these findings in larger studies including anti-tuberculosis medicated and unmedicated patient cohorts with other center nervous system infectious diseases is required for successful clinical translation. Copyright © 2015 Elsevier Inc. All rights reserved.

Genetic ablation of carotene oxygenases and consumption of lycopene or tomato powder diets modulates carotenoid and lipid metabolism in mice

PubMed Central

Ford, Nikki A.; Elsen, Amy C.; Erdman, John W.

2013-01-01

Carotene-15,15'-monooxygenase (CMO-I) cleaves β-carotene to form vitamin A while carotene-9’,10’-monooxygenase (CMO-II) preferentially cleaves non-provitamin A carotenoids. Recent reports indicate that beta-carotene metabolites regulate dietary lipid uptake while lycopene regulates peroxisome-proliferated activator receptor (PPAR) expression. To determine the physiologic consequences of carotenoids and their interactions with CMO-I and CMO-II, we characterized mammalian carotenoid metabolism, metabolic perturbations and lipid metabolism in female CMO-I−/− and CMO-II−/− mice fed lycopene or tomato-containing diets for 30 days. We hypothesized that there would be significant interactions between diet and genotype on carotenoid accumulation and lipid parameters. CMO-I−/− mice had higher levels of leptin, insulin and hepatic lipidosis, but lower levels of serum cholesterol. CMO-II−/− mice had increased tissue lycopene and phytofluene accumulation, reduced IGF-1 levels and cholesterol levels, but elevated liver lipids and cholesterol compared with WT mice. The diets did not modulate these genotypic perturbations, but lycopene and tomato powder did significantly decrease serum insulin-like growth factor-I. Tomato powder also reduced hepatic PPAR expression, independent of genotype. These data point to the pleiotropic actions of CMO-I and CMO-II supporting a strong role of these proteins in regulating tissue carotenoid accumulation and the lipid metabolic phenotype, as well as tomato carotenoid-independent regulation of lipid metabolism. PMID:24034573

Impact of a Traditional Dietary Supplement with Coconut Milk and Soya Milk on the Lipid Profile in Normal Free Living Subjects

PubMed Central

Ekanayaka, R. A. I.; Ekanayaka, N. K.; Perera, B.; De Silva, P. G. S. M.

2013-01-01

Background. The effects of coconut fat and soya fat on serum lipids are controversial. This study was designed to investigate the lipid effects of coconut milk and soya milk supplementation on the lipid profile of free living healthy subjects. Methods. Sixty (60) healthy volunteers aged 18–57 years were given coconut milk porridge (CMP) for 5 days of the week for 8 weeks, followed by a 2-week washout period, subsequent to which they received isoenergetic soya milk porridge (SMP) for 8 weeks. Results. The LDL (low density lipoprotein) levels decreased with CMP and reached statistical significance in the total study population and in the >130 baseline LDL group. The HDL (high density lipoprotein) levels rose significantly with CMP supplementation (P = 0.000). Conclusions. We conclude that coconut fat in the form of CM does not cause a detrimental effect on the lipid profile in the general population and in fact is beneficial due to the decrease in LDL and rise in HDL. SMP will be of benefit only in those whose baseline LDL levels are elevated. PMID:24282632

Postprandial lipid responses do not differ following consumption of butter or vegetable oil when consumed with omega-3 polyunsaturated fatty acids.

PubMed

Dias, Cintia B; Phang, Melinda; Wood, Lisa G; Garg, Manohar L

2015-04-01

Dietary saturated fat (SFA) intake has been associated with elevated blood lipid levels and increased risk for the development of chronic diseases. However, some animal studies have demonstrated that dietary SFA may not raise blood lipid levels when the diet is sufficient in omega-3 polyunsaturated fatty acids (n-3PUFA). Therefore, in a randomised cross-over design, we investigated the postprandial effects of feeding meals rich in either SFA (butter) or vegetable oil rich in omega-6 polyunsaturated fatty acids (n-6PUFA), in conjunction with n-3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triacylglycerol (TAG)] and n-3PUFA incorporation into plasma lipids over a 6-h period. The incremental area under the curve for plasma cholesterol, LDL-C, HDL-C, TAG and n-3PUFA levels over 6 h was similar in the n-6PUFA compared to SFA group. The postprandial lipemic response to saturated fat is comparable to that of n-6PUFA when consumed with n-3PUFA; however, sex-differences in response to dietary fat type are worthy of further attention.

Flavanol-rich lychee fruit extract alleviates diet-induced insulin resistance via suppressing mTOR/SREBP-1 mediated lipogenesis in liver and restoring insulin signaling in skeletal muscle.

PubMed

Liu, Hung-Wen; Wei, Chu-Chun; Chen, Yen-Ju; Chen, Yun-An; Chang, Sue-Joan

2016-10-01

An elevated intracellular lipid contents resulted from lipid oversupply links obesity to insulin resistance. Flavanol-rich lychee fruit extract, oligonol, exhibited anti-obesity property in vitro and in vivo; however, the effects of oligonol on peripheral lipid metabolism and insulin sensitivity have not been fully investigated. We hypothesized that oligonol alleviated insulin resistance via decreasing intracellular lipid contents in peripheral tissues. Dietary oligonol supplementation (20 or 200 mg/kg bw) reduced glucose and insulin levels, improved oral glucose tolerance, and suppressed inflammatory markers, MCP-1 and IL-6, in High-Fat diet (HFD) induced obese mice. Marked decreases in subcutaneous and visceral fat area, adipocyte size, and adipocyte released hormones including leptin and resistin by high-dose oligonol treatment were associated with downregulation of PPARγ gene expression. Significantly reduced intrahepatocellular lipid contents and hepatic triglyceride levels by oligonol (both doses) were associated with downregulation of mTOR/SREBP-1-mediated de novo lipogenesis. In skeletal muscle, oligonol enhanced Sirtuin1 protein expression and AMPKα activation, consequently resulted in reductions of intramuscular lipid contents and triglyceride levels and restoration of IRS-1 and AS160 phosphorylation. Oligonol reduced intracellular lipid contents in liver and skeletal muscle and suppressed inflammatory markers, thereby alleviating HFD-induced insulin resistance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High levels of anti-inflammatory and pro-resolving lipid mediators lipoxins and resolvins and declining docosahexaenoic acid levels in human milk during the first month of lactation

PubMed Central

2013-01-01

Background The fatty acid mixture of human milk is ideal for the newborn but little is known about its composition in the first few weeks of lactation. Of special interest are the levels of long-chain PUFAs (LCPUFAs), since these are essential for the newborn’s development. Additionally, the LCPUFAs arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are precursors for lipid mediators which regulate inflammation. Methods We determined the composition of 94 human milk samples from 30 mothers over the first month of lactation for fatty acids using GC-MS and quantified lipid mediators using HPLC-MS/MS. Results Over the four weeks period, DHA levels decreased, while levels of γC18:3 and αC18:3 steadily increased. Intriguingly, we found high concentrations of lipid mediators and their hydroxy fatty acid precursors in human milk, including pro-inflammatory leukotriene B4 (LTB4) and anti-inflammatory and pro-resolving lipoxin A4 (LXA4), resolvin D1 (RvD1) and resolvin E1 (RvE1). Lipid mediator levels were stable with the exception of two direct precursors. Conclusions Elevated levels of DHA right after birth might represent higher requirements of the newborn and the high content of anti-inflammatory and pro-resolving lipid mediators and their precursors may indicate their role in neonatal immunity and may be one of the reasons for the advantage of human milk over infant formula. PMID:23767972

Dietary deficiency of vitamin E aggravates retinal ganglion cell death in experimental glaucoma of rats.

PubMed

Ko, Mei-Lan; Peng, Pai-Huei; Hsu, Shens-Yao; Chen, Chau-Fong

2010-09-01

Investigate the effect of dietary vitamin E (Vit E) on the retinas of a rat model of induced glaucoma, in which surgically induced elevation of intraocular pressure (IOP) is associated with an increase in reactive oxygen species. Rats were fed a standard chow, Vit E-supplemented diet, or Vit E-deficient diet and subjected to surgically induced IOP elevation (or sham surgery) for five weeks. The retinal ganglion cells (RGCs) were subjected to retrograde fluorescent tracer labeling. The mean number of RGCs of rats on the standard chow, Vit E-supplemented diet, and Vit E-deficient diet were 79.6%, 78.6%, and 71.3% of controls, respectively. Lipid peroxidation of the retinas of rats given a Vit E-deficient diet were significantly higher after IOP elevation for three days (14.42 +/- 0.25 microM, P = 0.016) and five weeks (10.46 +/- 0.11 microM, p = 0.042), compared to rats given standard chow (11.37 +/- 0.31 microM; 8.95 +/- 0.16 microM). Compared with rats given standard chow, rats given a Vit E-deficient diet had significantly elevated concentrations of glutathione (p = 0.032), but no significant differences in the levels of total superoxide dismutase (SOD), Cu/Zn SOD, or catalase activities three days after IOP elevation. Rats fed a Vit E-deficient diet with surgically induced IOP elevation experience significantly more RGC death than rats fed a normal diet. This phenomenon may be related to the increased level of lipid peroxidation in Vit E-deficient rats.

Increased levels of palmitoylethanolamide and other bioactive lipid mediators and enhanced local mast cell proliferation in canine atopic dermatitis

PubMed Central

2014-01-01

Background Despite the precise pathogenesis of atopic dermatitis (AD) is unknown, an immune dysregulation that causes Th2-predominant inflammation and an intrinsic defect in skin barrier function are currently the two major hypotheses, according to the so-called outside-inside-outside model. Mast cells (MCs) are involved in AD both by releasing Th2 polarizing cytokines and generating pruritus symptoms through release of histamine and tryptase. A link between MCs and skin barrier defects was recently uncovered, with histamine being found to profoundly contribute to the skin barrier defects. Palmitoylethanolamide and related lipid mediators are endogenous bioactive compounds, considered to play a protective homeostatic role in many tissues: evidence collected so far shows that the anti-inflammatory effect of palmitoylethanolamide depends on the down-modulation of MC degranulation. Based on this background, the purpose of the present study was twofold: (a) to determine if the endogenous levels of palmitoylethanolamide and other bioactive lipid mediators are changed in the skin of AD dogs compared to healthy animals; (b) to examine if MC number is increased in the skin of AD dogs and, if so, whether it depends on MC in-situ proliferation. Results The amount of lipid extract expressed as percent of biopsy tissue weight was significantly reduced in AD skin while the levels of all analyzed bioactive lipid mediators were significantly elevated, with palmitoylethanolamide showing the highest increase. In dogs with AD, the number of MCs was significantly increased in both the subepidermal and the perifollicular compartments and their granule content was significantly decreased in the latter. Also, in situ proliferation of MCs was documented. Conclusions The levels of palmitoylethanolamide and other bioactive lipid mediators were shown to increase in AD skin compared to healthy samples, leading to the hypothesis that they may be part of the body’s innate mechanisms to maintain cellular homeostasis when faced with AD-related inflammation. In particular, the increase may be considered a temptative response to down-regulating the observed elevation in the number, functionality and proliferative state of MCs in the skin of AD dogs. Further studies are warranted to confirm the hypothesis. PMID:24423192

Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study

PubMed Central

Starling, Anne P.; Engel, Stephanie M.; Whitworth, Kristina W.; Richardson, David B.; Stuebe, Alison M.; Daniels, Julie L.; Haug, Line Småstuen; Eggesbø, Merete; Becher, Georg; Sabaredzovic, Azemira; Thomsen, Cathrine; Wilson, Ralph E.; Travlos, Gregory S.; Hoppin, Jane A.; Baird, Donna D.; Longnecker, Matthew P.

2013-01-01

Background Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. Methods This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003–2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. Results Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2 mg/dL per interquartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per interquartile shift (95% CI=2.5, 4.9). Conclusion Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal. PMID:24189199

Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study.

PubMed

Starling, Anne P; Engel, Stephanie M; Whitworth, Kristina W; Richardson, David B; Stuebe, Alison M; Daniels, Julie L; Haug, Line Småstuen; Eggesbø, Merete; Becher, Georg; Sabaredzovic, Azemira; Thomsen, Cathrine; Wilson, Ralph E; Travlos, Gregory S; Hoppin, Jane A; Baird, Donna D; Longnecker, Matthew P

2014-01-01

Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI=2.5, 4.9). Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal. © 2013.

The potential behavioral and economic impacts of widespread HMG-CoA reductase inhibitor (statin) use.

PubMed

Gendle, Mathew H

2016-12-01

Dyslipidemia is a common pathology throughout the industrialized world, and HMG-CoA reductase inhibitors (statins) are often administered to treat elevated lipid levels. Substantial concern has been raised regarding the aggressive clinical lowering of cholesterol, particularly in light of a growing body of research linking low circulating lipid levels with negative behavioral outcomes in both human samples and non-human primate models. In 2009, Goldstein and colleagues tentatively speculated that the greed, impulsiveness, and lack of foresight that lead to the worldwide economic collapse in 2007-2008 could have been caused (in part) by depressed population cholesterol levels resulting from the widespread use of statins by workers in the financial services industry. This paper reviews the literature that links low circulating lipid levels with neurobehavioral dysfunction, develops Goldstein and colleagues' initial speculation into a formal hypothesis, and proposes several specific studies that could rigorously empirically evaluate this hypothesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats.

PubMed

Sathiavelu, Jayanthi; Senapathy, Giftson Jebakkan; Devaraj, Rajkumar; Namasivayam, Nalini

2009-06-01

To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

Association between APOE, SCARB1, PPARα polymorphisms and serum lipids in a population of Lithuanian adults

PubMed Central

2013-01-01

Background Dyslipidemia is one of several known risk factors for coronary heart disease, a leading cause of death in Lithuania. Blood lipid levels are influenced by multiple genetic and environmental factors. Epidemiological studies demonstrated the impact of nutrition on lipid levels within the Lithuanian population although the role of genetic factors for dyslipidemias has not yet been studied. The objective of this study was to assess the distribution of the APOE, SCARB1, PPARα genotypes in the Lithuanian adult population and to determine the relationship of these genotypes with dyslipidemia. Methods A cross-sectional health survey was carried out in a representative random sample of the Lithuanian population aged 25–64 (n=1030). A variety of single-nucleotide polymorphisms (SNPs) of the APOE (rs429358 and rs7412), SCARB1 (rs5888) and PPARα (rs1800206) genes were assessed using real-time polymerase chain reaction. Serum lipids were determined using enzymatic methods. Results/Principal findings Men and women with the APOE2 genotype had the lowest level of total and low-density lipoprotein cholesterol (LDL-C). Men with the APOE2 genotype had significantly higher levels of triglycerides (TG) than those with the APOE3 genotype. In men, the carriers of the APOE4 genotype had higher odds ratios (OR) of reduced (<1.0 mmol/L) high density lipoprotein cholesterol (HDL-C) levels versus APOE3 carriers (OR=1.98; 95% CI=1.05-3.74). The odds of having elevated (>1.7 mmol/L) TG levels was significantly lower in SCARB1 genotype CT carriers compared to men with the SCARB1 genotype CC (OR=0.50; 95% CI=0.31-0.79). In men, carriers of the PPARα genotype CG had higher OR of elevated TG levels versus carriers of PPARα genotype CC (OR=2.67; 95% CI=1.15-6.16). The odds of having high LDL-C levels were lower in women with the APOE2 genotype as compared to APOE3 genotype carriers (OR=0.35; 95% CI=0.22-0.57). Conclusions/Significance Our data suggest a gender difference in the associations between APOE, SCARB1, PPARα genotypes and lipid levels. In men, the APOE4 genotype and PPARα genotype CG were correlated with an atherogenic lipid profile while the SCARB1 genotype CT had an atheroprotective effect. In women, APOE2 carriers had the lowest odds of high LDL-C. PMID:23919842

Betaine Attenuates Alcohol-Induced Pancreatic Steatosis.

PubMed

Yang, Wenjuan; Gao, Jinhang; Tai, Yang; Chen, Meng; Huang, Luming; Wen, Shilei; Huang, Zhiyin; Liu, Rui; Li, Jing; Tang, Chengwei

2016-07-01

To explore the effect of betaine on alcoholic pancreatic steatosis and its mechanism. Rats were randomly assigned to control, ethanol, or ethanol + betaine groups. Changes in pancreatic morphology; serum lipid levels; and pancreatic lipid, amylase and lipase levels were determined. The serum and adipose tissue adiponectin level was measured by an enzyme-linked immunoassay. Adiponectin receptor-1 (AdipoR1), AdipoR2, sterol regulatory element binding protein-1c (SREBP-1c), SREBP-2, and fatty acid synthetase expression levels were quantified. The SREBP-1c expression in SW1990 cells treated with various concentrations of ethanol or ethanol plus betaine and/or adiponectin was assessed. Alcohol-induced changes in pancreatic morphology were attenuated by betaine. Pancreatic triglyceride, free fatty acid and expression levels of SREBP-1c and fatty acid synthetase were elevated after ethanol feeding but remained at control levels after betaine supplementation. Alcohol-induced decreases in serum and adipose tissue adiponectin, pancreatic AdipoR1, amylase, and lipase were attenuated by betaine. Serum triglyceride and free fatty acid levels were elevated after alcohol consumption and remained higher after betaine supplementation compared with controls. Betaine and/or adiponectin suppressed alcohol-induced SREBP-1c upregulation in vitro. Betaine attenuated alcoholic-induced pancreatic steatosis most likely by suppressing pancreatic SREBP-1c both directly and through the restoration of adiponectin signaling.

Testicular membrane lipid damage by complex mixture of leachate from municipal battery recycling site as indication of idiopathic male infertility in rat

PubMed Central

Oboh, Ganiyu; Akindahunsi, Akintunde A.

2013-01-01

Leachate from a municipal battery recycling site is a potent source of mixed-metal released into the environment. The present study investigated the degree at which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected the lipid membrane of the testes in in vitro experiment. The results showed elevated level of mixed-metals over the permissible levels in drinking water, as recommended by regulatory authorities. In the leachate samples, the levels of malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05) increased in rat testes in a dose-dependent manner. MDA induced by the municipal auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular lipid membrane capacity was compromised following treatment with leachate from the municipal battery recycling site, implicating mixed-metal exposure as the causative agent of testicular damage and male infertility. PMID:24678257

Testicular membrane lipid damage by complex mixture of leachate from municipal battery recycling site as indication of idiopathic male infertility in rat.

PubMed

Akintunde, Jacob K; Oboh, Ganiyu; Akindahunsi, Akintunde A

2013-12-01

Leachate from a municipal battery recycling site is a potent source of mixed-metal released into the environment. The present study investigated the degree at which mixed-metal exposure to the municipal auto-battery leachate (MABL) and to the Elewi Odo municipal auto-battery recycling site leachate (EOMABRL) affected the lipid membrane of the testes in in vitro experiment. The results showed elevated level of mixed-metals over the permissible levels in drinking water, as recommended by regulatory authorities. In the leachate samples, the levels of malondialdehyde (MDA), a biomarker of lipid damage, was significantly (p<0.05) increased in rat testes in a dose-dependent manner. MDA induced by the municipal auto-battery leachate (MABL) was significantly (p<0.05) higher than the leachate from Elewi Odo municipal auto-battery recycling site (EOMABRL). The testicular lipid membrane capacity was compromised following treatment with leachate from the municipal battery recycling site, implicating mixed-metal exposure as the causative agent of testicular damage and male infertility.

Gender differences in the lipid profile of dyslipidemic subjects.

PubMed

Kolovou, Genovefa D; Anagnostopoulou, Katherine K; Damaskos, Dimitris S; Bilianou, Helen I; Mihas, Constantinos; Milionis, Haralampos J; Kostakou, Peggy M; Cokkinos, Dennis V

2009-03-01

We evaluated the gender-associated differences in lipid profile of subjects intended to receive lipid-lowering therapy with emphasis on the associations between triglycerides (TG) and other plasma lipid variables. Lipid profiles of 1385 patients [aged 55+/-11 years, 549 women (40%)] were evaluated. Eligible subjects fulfilled one or more of the following criteria: total cholesterol (TC)>or=6.2 mmol/l, TG>or=1.7 mmol/l, and high-density lipoprotein cholesterol (HDL-C)<1.0 mmol/l. Patients were divided into subgroups according to TG and HDL-C levels. Women aged on average 3.5 years older, had higher TC and HDL-C, lower TG and a correspondingly lower TC/HDL-C ratio than men. High TG and low HDL-C in tandem appeared twice more frequently in men. Inverse correlations between HDL-C and TG levels were found to exist in the entire cohort (r=-0.354, p<0.001) and in all various subgroups. In the subgroup with TG<1.7 mmol/l, women had higher TC and HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. In the subgroup with TG>or=1.7 mmol/l, women had higher TC and HDL-C levels and lower TC/HDL ratio compared with men. In the subgroup with HDL-C>or=1.0 mmol/l women had higher HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. Elevated TG levels and low HDL-C in tandem are common lipid abnormalities in the clinical setting of primary and secondary preventions. Gender-associated differences in the lipid profile are evident in subjects presenting with dyslipidemia and might be of potential relevance for diagnostics and therapy for the prevention of atherosclerosis.

Response of sunshine bass to ration at elevated culture temperature

USDA-ARS?s Scientific Manuscript database

Temperature and ammonia increase dramatically during summer production of sunshine bass. Global temperatures are projected to increase. A factorial experiment investigated the effects of three digestible protein (DP; 33, 40, 47%), two lipid (L; 10, 18 %) and two ration levels (satiation, restricted)...

Dioxin concentrations in breast milk of Vietnamese nursing mothers: a survey four decades after the herbicide spraying.

PubMed

Tai, Pham The; Nishijo, Muneko; Kido, Teruhiko; Nakagawa, Hideaki; Maruzeni, Shoko; Naganuma, Rie; Anh, Nguyen Thi Nguyet; Morikawa, Yuko; Luong, Hoang Van; Anh, Tran Hai; Hung, Nguyen Ngoc; Son, Le Ke; Tawara, Kenji; Nishijo, Hisao

2011-08-01

In an operation by United States Armed Forces during 1961 to 1971, large quantities of herbicides were sprayed in South Vietnam. These herbicides contained 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD), the most toxic congener of dioxins. Several decades after the herbicide spraying ceased, dioxin concentrations in the environment and human remained elevated in the sprayed areas. Breast milk samples from 520 nursing mothers residing in areas including the hot spots as well as the sprayed and unsprayed areas were collected to quantify the levels of dioxins. The total toxic equivalents of 2,3,7,8-substitued PCDDs/PCDFs in breast milk of mothers living in the hot spots, and the sprayed and unsprayed areas were 14.10 pg/g lipid, 10.89 pg/g lipid, and 4.09 pg/g lipid for primiparae and 11.48 pg/g lipid, 7.56 pg/g lipid, and 2.84 pg/g lipid for multiparae, respectively, with significant differences in the values among the three areas. In the hot spots, dioxin levels were highly correlated with the residency of mothers after adjustment for their age and parity.

Chromium picolinate inhibits cholesterol-induced stimulation of platelet aggregation in hypercholesterolemic rats.

PubMed

Seif, A A

2015-06-01

Hypercholesterolemia indirectly increases the risk of myocardial infarction by enhancing platelet aggregation. Chromium has been shown to lower plasma lipids. This study was designed to investigate whether chromium inhibits platelet aggregation under hypercholesterolemic conditions. Albino rats were divided into four groups: control rats fed with a normolipemic diet (NLD group), chromium-supplemented rats fed with NLD (NLD + Cr group), rats fed with a high-fat diet (HF group), and chromium-supplemented rats fed with HF (HF + Cr group). After 10 weeks, blood was collected to determine adenosine diphosphate and collagen-induced platelet aggregation and plasma levels of total cholesterol, triglycerides, high-density lipoprotein cholesterol, apolipoprotein A1, apolipoprotein B, and thromboxane B2. Low-density lipoprotein cholesterol was calculated by Friedewald formula. High-fat diet animals displayed significant elevation of plasma lipids and platelet aggregation which was normalized to control levels by chromium supplementation. Chromium supplementation in normolipemic (NLD + Cr) rats did not produce significant changes in either plasma lipids or platelet activity. Chromium supplementation to hypercholesterolemic rats improves the lipid profile and returns platelet hyperaggregability to control levels. This normalization is mostly due to a reduction in plasma cholesterol level.

Effect of N-benzoyl-d-phenylalanine on lipid profile in liver of neonatal streptozotocin diabetic rats.

PubMed

Pari, Leelavinothan; Ashokkumar, Natarajan

2005-10-01

The effect of N-benzoyl-d-phenylalanine (NBDP) and metformin combination treatment on liver lipids and lipid peroxidation markers was studied in neonatal streptozotocin (nSTZ) diabetic rats. Oral administration of NBDP (50, 100 and 200 mg/kg body weight) and metformin (500 mg/kg body weight) for 6 weeks significantly reduced the elevated blood glucose, liver cholesterol, triglycerides, free fatty acids and phospholipids. The combination treatment also caused a significant decrease in hepatic hydroxymethyl glutaryl-coenzyme A reductase, Thiobarbituric Acid Reactive Substances (TBARS) and significant increase in reduced glutathione levels. The results show that NBDP and metformin improve the hepatic lipid profile and antioxidant status in nSTZ diabetic rats. Combination treatment was more effective than either drug alone.

A Chinese herbal medicine, jia-wei-xiao-yao-san, prevents dimethylnitrosamine-induced hepatic fibrosis in rats.

PubMed

Chien, Shu-Chen; Chang, Wei-Chiao; Lin, Pu-Hua; Chang, Wei-Pin; Hsu, Shih-Chung; Chang, Jung-Chen; Wu, Ya-Chieh; Pei, Jin-Kuo; Lin, Chia-Hsien

2014-01-01

Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.

Metabolic profiling of muscle contraction in lean compared with obese rodents.

PubMed

Thyfault, John P; Cree, Melanie G; Tapscott, Edward B; Bell, Jill A; Koves, Timothy R; Ilkayeva, Olga; Wolfe, Robert R; Dohm, G Lynis; Muoio, Deborah M

2010-09-01

Interest in the pathophysiological relevance of intramuscular triacylglycerol (IMTG) accumulation has grown from numerous studies reporting that abnormally high glycerolipid levels in tissues of obese and diabetic subjects correlate negatively with glucose tolerance. Here, we used a hindlimb perfusion model to examine the impact of obesity and elevated IMTG levels on contraction-induced changes in skeletal muscle fuel metabolism. Comprehensive lipid profiling was performed on gastrocnemius muscles harvested from lean and obese Zucker rats immediately and 25 min after 15 min of one-legged electrically stimulated contraction compared with the contralateral control (rested) limbs. Predictably, IMTG content was grossly elevated in control muscles from obese rats compared with their lean counterparts. In muscles of obese (but not lean) rats, contraction resulted in marked hydrolysis of IMTG, which was then restored to near resting levels during 25 min of recovery. Despite dramatic phenotypical differences in contraction-induced IMTG turnover, muscle levels of diacylglycerol (DAG) and long-chain acyl-CoAs (LCACoA) were surprisingly similar between groups. Tissue profiles of acylcarnitine metabolites suggested that the surfeit of IMTG in obese rats fueled higher rates of fat oxidation relative to the lean group. Muscles of the obese rats had reduced lactate levels immediately following contraction and higher glycogen resynthesis during recovery, consistent with a lipid-associated glucose-sparing effect. Together, these findings suggest that contraction-induced mobilization of local lipid reserves in obese muscles promotes beta-oxidation, while discouraging glucose utilization. Further studies are necessary to determine whether persistent oxidation of IMTG-derived fatty acids contributes to systemic glucose intolerance in other physiological settings.

Is there any relationship between coronary artery disease and postprandial triglyceride levels?

PubMed

Atar, Inci Aslı; Atar, Ilyas; Aydınalp, Alp; Ertan, Cağatay; Bozbaş, Hüseyin; Ozin, Bülent; Yıldırır, Aylin; Müderrisoğlu, Haldun

2011-05-01

We aimed to evaluate the relationship between postprandial triglyceride (PPTG) levels and coronary artery disease (CAD). A total of 80 patients were included in this prospective cohort study. Oral lipid loading was used in order to measure PPTG levels. In the fasting state and after the high fat breakfast, triglyceride levels were measured by enzymatic methods at 2nd, 4th, 6th and 8th hours. We made subgroup analysis to show the effects of lipid loading on triglyceride levels in patients with and without fasting hypertriglyceridemia. We evaluated triglyceride levels and changes of triglyceride levels in percentages after lipid loading using a general linear model for repeated measures. Sample size analysis was performed. Baseline clinical, demographic and laboratory characteristics of both groups were similar. The peak triglyceride levels were seen at the 4th hour in both groups. Triglyceride levels were significantly increased after lipid-rich-breakfast loading compared to baseline levels in both groups (p<0.001) but these changes were not significant (p=0.279). In patients with elevated fasting triglyceride levels, the area under the plasma triglyceride concentration curve was significantly larger in CAD group than control group (334±103 vs. 233±58 mg/dl, p=0.02). Our data show that in patients who have a high fasting triglyceride level, high levels of PPTG may be related to CAD, however high PPTG levels are not related to CAD in patients with normal fasting levels of triglyceride.

Lp(a) (Lipoprotein(a)) Levels Predict Progression of Carotid Atherosclerosis in Subjects With Atherosclerotic Cardiovascular Disease on Intensive Lipid Therapy: An Analysis of the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) Carotid Magnetic Resonance Imaging Substudy-Brief Report.

PubMed

Hippe, Daniel S; Phan, Binh An P; Sun, Jie; Isquith, Daniel A; O'Brien, Kevin D; Crouse, John R; Anderson, Todd; Huston, John; Marcovina, Santica M; Hatsukami, Thomas S; Yuan, Chun; Zhao, Xue-Qiao

2018-03-01

To assess whether Lp(a) (lipoprotein(a)) levels and other lipid levels were predictive of progression of atherosclerosis burden as assessed by carotid magnetic resonance imaging in subjects who have been treated with LDL-C (low-density lipoprotein cholesterol)-lowering therapy and participated in the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes). AIM-HIGH was a randomized, double-blind study of subjects with established vascular disease, elevated triglycerides, and low HDL-C (high-density lipoprotein cholesterol). One hundred fifty-two AIM-HIGH subjects underwent both baseline and 2-year follow-up carotid artery magnetic resonance imaging. Plaque burden was measured by the percent wall volume (%WV) of the carotid artery. Associations between annualized change in %WV with baseline and on-study (1 year) lipid variables were evaluated using multivariate linear regression and the Bonferroni correction to account for multiple comparisons. Average %WV at baseline was 41.6±6.8% and annualized change in %WV over 2 years ranged from -3.2% to 3.7% per year (mean: 0.2±1.1% per year; P =0.032). Increases in %WV were significantly associated with higher baseline Lp(a) (β=0.34 per 1-SD increase of Lp(a); 95% confidence interval, 0.15-0.52; P <0.001) after adjusting for clinical risk factors and other lipid levels. On-study Lp(a) had a similar positive association with %WV progression (β=0.33; 95% confidence interval, 0.15-0.52; P <0.001). Despite intensive lipid therapy, aimed at aggressively lowering LDL-C to <70 mg/dL, carotid atherosclerosis continued to progress as assessed by carotid magnetic resonance imaging and that elevated Lp(a) levels were independent predictors of increases in atherosclerosis burden. © 2018 American Heart Association, Inc.

Effects of small interfering RNA-mediated hepatic glucagon receptor inhibition on lipid metabolism in db/db mice.

PubMed

Han, Seongah; Akiyama, Taro E; Previs, Stephen F; Herath, Kithsiri; Roddy, Thomas P; Jensen, Kristian K; Guan, Hong-Ping; Murphy, Beth A; McNamara, Lesley A; Shen, Xun; Strapps, Walter; Hubbard, Brian K; Pinto, Shirly; Li, Cai; Li, Jing

2013-10-01

Hepatic glucose overproduction is a major characteristic of type 2 diabetes. Because glucagon is a key regulator for glucose homeostasis, antagonizing the glucagon receptor (GCGR) is a possible therapeutic strategy for the treatment of diabetes mellitus. To study the effect of hepatic GCGR inhibition on the regulation of lipid metabolism, we generated siRNA-mediated GCGR knockdown (si-GCGR) in the db/db mouse. The hepatic knockdown of GCGR markedly reduced plasma glucose levels; however, total plasma cholesterol was increased. The detailed lipid analysis showed an increase in the LDL fraction, and no change in VLDL HDL fractions. Further studies showed that the increase in LDL was the result of over-expression of hepatic lipogenic genes and elevated de novo lipid synthesis. Inhibition of hepatic glucagon signaling via siRNA-mediated GCGR knockdown had an effect on both glucose and lipid metabolism in db/db mice.

Influence of membrane phospholipid composition and structural organization on spontaneous lipid transfer between membranes.

PubMed

Pankov, R; Markovska, T; Antonov, P; Ivanova, L; Momchilova, A

2006-09-01

Investigations were carried out on the influence of phospholipid composition of model membranes on the processes of spontaneous lipid transfer between membranes. Acceptor vesicles were prepared from phospholipids extracted from plasma membranes of control and ras-transformed fibroblasts. Acceptor model membranes with manipulated levels of phosphatidylethanolamine (PE), sphingomyelin and phosphatidic acid were also used in the studies. Donor vesicles were prepared of phosphatidylcholine (PC) and contained two fluorescent lipid analogues, NBD-PC and N-Rh-PE, at a self-quenching concentration. Lipid transfer rate was assessed by measuring the increase of fluorescence in acceptor membranes due to transfer of fluorescent lipid analogues from quenched donor to unquenched acceptor vesicles. The results showed that spontaneous NBD-PC transfer increased upon fluidization of acceptor vesicles. In addition, elevation of PE concentration in model membranes was also accompanied by an increase of lipid transfer to all series of acceptor vesicles. The results are discussed with respect to the role of lipid composition and structural order of cellular plasma membranes in the processes of spontaneous lipid exchange between membrane bilayers.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penrose, Harrison; Heller, Sandra; Cable, Chloe

The proliferation of colon cancer cells is mediated in part by epidermal growth factor receptor (EGFR) signaling and requires sustained levels of cellular energy to meet its high metabolic needs. Intracellular lipid droplets (LDs) are a source of energy used for various cellular functions and they are elevated in density in human cancer, yet their regulation and function are not well understood. Here, in human colon cancer cells, EGF stimulates increases in LD density, which depends on EGFR expression and activation as well as the individual cellular capacity for lipid synthesis. Increases in LDs are blockaded by inhibition of PI3K/mTORmore » and PGE2 synthesis, supporting their dependency on select upstream pathways. In colon cancer cells, silencing of the FOXO3 transcription factor leads to down regulation of SIRT6, a negative regulator of lipid synthesis, and consequent increases in the LD coat protein PLIN2, revealing that increases in LDs depend on loss of FOXO3/SIRT6. Moreover, EGF stimulates loss of FOXO3/SIRT6, which is blockaded by the inhibition of upstream pathways as well as lipid synthesis, revealing existence of a negative regulatory loop between LDs and FOXO3/SIRT6. Elevated LDs are utilized by EGF treatment and their depletion through the inhibition of lipid synthesis or silencing of PLIN2 significantly attenuates proliferation. This novel mechanism of proliferative EGFR signaling leading to elevated LD density in colon cancer cells could potentially be therapeutically targeted for the treatment of tumor progression. - Highlights: • In colon cancer cells, EGFR activation leads to increases in LD density. • EGFR signaling includes PI3K/mTOR and PGE2 leading to lipid synthesis. • Increases in LDs are controlled by a negative regulatory loop with FOXO3/SIRT6. • EGFR mediated colon cancer cell proliferation depends on increased LD density.« less

National lipid association recommendations for patient-centered management of dyslipidemia: part 1--full report.

PubMed

Jacobson, Terry A; Ito, Matthew K; Maki, Kevin C; Orringer, Carl E; Bays, Harold E; Jones, Peter H; McKenney, James M; Grundy, Scott M; Gill, Edward A; Wild, Robert A; Wilson, Don P; Brown, W Virgil

2015-01-01

The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non-high-density lipoprotein cholesterol and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Uteroplacental insufficiency after bilateral uterine artery ligation in the rat: impact on postnatal glucose and lipid metabolism and evidence for metabolic programming of the offspring by sham operation.

PubMed

Nüsken, Kai-Dietrich; Dötsch, Jörg; Rauh, Manfred; Rascher, Wolfgang; Schneider, Holm

2008-03-01

Ligation of the uterine arteries (LIG) in rats serves as a model of intrauterine growth restriction and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia, and adiposity in the offspring. Its impact on lipid metabolism has been less well investigated. We compared parameters of glucose and lipid metabolism and glucocorticoid levels in the offspring of dams that underwent either LIG or sham operation (SOP) with those of untreated controls. Blood parameters including insulin, leptin, and visfatin as well as body weight, food intake, and creatinine clearance were recorded up to an age of 30 wk. Glucose tolerance tests were performed, and both leptin and visfatin expression in liver, muscle, and epididymal and mesenteric fat was quantified by RT-PCR. After catch-up growth, weight gain of all groups was similar, despite lower food intake of the LIG rats. LIG offspring showed impaired glucose tolerance from the age of 15 wk as well as elevated glycosylated hemoglobin and corticosterone levels. However, the body fat content of both LIG and SOP animals increased relative to controls, and both showed elevated triglyceride, total cholesterol, and leptin levels as well as a reduced proportion of high-density lipoprotein cholesterol. Thus, use of the LIG model requires both SOP and untreated controls. Although only LIG is associated with impaired glucose tolerance, pathogenic programming of the lipid metabolism can also be induced by SOP. Visfatin does not appear to be involved in the disturbed glucose metabolism after intrauterine growth restriction and may represent only a marker of fat accumulation.

[Becoming more "goal-oriented" in therapy of dyslipidemias: results of the Hungarian MULTI GAP 2010].

PubMed

Reiber, István; Paragh, György; Márk, László; Pados, Gyula

2011-05-22

Previous studies have found that many high-risk patients are not achieving their LDL-cholesterol goals, and many patients, despite being treated with lipid-lowering therapy, also have elevated triglycerides and/or low levels of HDL-cholesterol. Authors analyzed the treatment strategies for dyslipidemic subjects following cardiovascular events similarly to their former survey from 2008 and 2009. In the MULTI GAP (MULTI Goal Attainment Problem) 2010 trial data from standard and structured questionnaires of 2332 patients were processed. Authors analyzed the proportion of the patients reaching target levels for total cholesterol, LDL-C, HDL-C, A-C (atherogen cholesterol) and triglyceride. 15% (n = 355) of the patients did not receive any lipid lowering treatment. 44% of the patients treated by specialists reached the target LDL-C level of 2.5 mmol/l. In "high risk" group target levels for HDL-C were reached by 61% of the patients, and for triglyceride by 43% of the subjects. 43% of the patients with the best compliance (>90%) reached the target LDL-C level of 2.5 mmol/l. There is a need for more effective lipid lowering therapy with more frequent use of higher doses of statins or combinations of lipid lowering drugs.

Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.

PubMed

Xu, Jin; Casas-Ferreira, Ana M; Ma, Yun; Sen, Arundhuti; Kim, Min; Proitsi, Petroula; Shkodra, Maltina; Tena, Maria; Srinivasan, Parthi; Heaton, Nigel; Jassem, Wayel; Legido-Quigley, Cristina

2015-12-04

Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.

Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

PubMed

Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong; Liu, Wei

2017-03-01

Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography-mass spectrometry (MS) and liquid chromatography-MS. Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. Copyright © 2017 by the Endocrine Society

Discovery of Novel Lipid Profiles in PCOS: Do Insulin and Androgen Oppositely Regulate Bioactive Lipid Production?

PubMed Central

Li, Shengxian; Chu, Qianqian; Ma, Jing; Sun, Yun; Tao, Tao; Huang, Rong; Liao, Yu; Yue, Jiang; Zheng, Jun; Wang, Lihua; Xue, Xinli; Zhu, Mingjiang; Kang, Xiaonan; Yin, Huiyong

2017-01-01

Abstract Context: Polycystic ovary syndrome (PCOS) is a complex syndrome showing clinical features of an endocrine/metabolic disorder, including hyperinsulinemia and hyperandrogenism. Polyunsaturated fatty acids (PUFAs) and their derivatives, both tightly linked to PCOS and obesity, play important roles in inflammation and reproduction. Objective: This study aimed to investigate serum lipid profiles in newly diagnosed patients with PCOS using lipidomics and correlate these features with the hyperinsulinemia and hyperandrogenism associated with PCOS and obesity. Design and Setting: Thirty-two newly diagnosed women with PCOS and 34 controls were divided into obese and lean subgroups. A PCOS rat model was used to validate results of the human studies. Main Outcome Measures: Serum lipid profiles, including phospholipids, free fatty acids (FFAs), and bioactive lipids, were analyzed using gas chromatography–mass spectrometry (MS) and liquid chromatography–MS. Results: Elevation in phosphatidylcholine and a concomitant decrease in lysophospholipid were found in obese patients with PCOS vs lean controls. Obese patients with PCOS had decreased PUFA levels and increased levels of long-chain saturated fatty acids vs lean controls. Serum bioactive lipids downstream of arachidonic acid were increased in obese controls, but reduced in both obese and lean patients with PCOS vs their respective controls. Conclusions: Patients with PCOS showed abnormal levels of phosphatidylcholine, FFAs, and PUFA metabolites. Circulating insulin and androgens may have opposing effects on lipid profiles in patients with PCOS, particularly on the bioactive lipid metabolites derived from PUFAs. These clinical observations warrant further studies of the molecular mechanisms and clinical implications of PCOS and obesity. PMID:27886515

Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Di-xian, E-mail: luodixian_2@163.com; Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan; First People's Hospital of Chenzhou City, Chenzhou 423000, Hunan

Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different staticmore » pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were upregulated. Conclusion: Static pressures stimulate ox-LDL-induced cholesterol accumulation in cultured VSMCs through decreasing caveolin-1 expression via inducing the maturation and nuclear translocation of SREBP-1.« less

Low Urinary Iodine Concentrations Associated with Dyslipidemia in US Adults.

PubMed

Lee, Kyung Won; Shin, Dayeon; Song, Won O

2016-03-17

Iodine is an essential component of the thyroid hormone which plays crucial roles in healthy thyroid function and lipid metabolism. However, the association between iodine status and dyslipidemia has not been well established at a population level. We aimed to test the hypothesis that the odds of dyslipidemia including elevated total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and apolipoprotein B, and lowered high-density lipoprotein (HDL) cholesterol and HDL/LDL ratio are associated with urinary iodine concentration (UIC) in a population perspective. Data of 2495 US adults (≥20 years) in the National Health and Nutrition Examination Survey 2007-2012 were used in this study. Two subgroups (i.e., UIC below vs. above the 10th percentile) were compared of dyslipidemia as defined based on NCEP ATP III guidelines. The differences between the groups were tested statistically by chi-square test, simple linear regressions, and multiple logistic regressions. Serum lipid concentrations differed significantly between two iodine status groups when sociodemographic and lifestyle covariates were controlled (all, p < 0.05). Those with the lowest decile of UIC were more likely to be at risk for elevated total cholesterol (>200 mg/dL) (adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI): 1.03-2.23) and elevated LDL cholesterol (>130 mg/dL) (AOR = 1.58, 95% CI: 1.11-2.23) and lowered HDL/LDL ratio (<0.4) (AOR = 1.66, 95% CI: 1.18-2.33), compared to those with UIC above the 10th percentile. In US adults, low UIC was associated with increased odds for dyslipidemia. Findings of the present cross-sectional study with spot urine samples highlight the significant association between UIC and serum lipids at population level, but do not substantiate a causal relationship. Further investigations are warranted to elucidate the causal relationship among iodine intakes, iodine status, and serum lipid profiles.

Sphingolipids Are Required for Efficient Triacylglycerol Loss in Conjugated Linoleic Acid Treated Adipocytes

PubMed Central

Wang, Wei; Fromm, Michael

2015-01-01

Conjugated linoleic acid (CLA) reduces adiposity in human and mouse adipocytes. This outcome is achieved through a variety of biological responses including increased energy expenditure and fatty acid oxidation, increased inflammation, repression of fatty acid biosynthesis, attenuated glucose transport, and apoptosis. In the current study, profiling of 261 metabolites was conducted to gain new insights into the biological pathways responding to CLA in 3T3-L1 adipocytes. Sphinganine and sphingosine levels were observed to be highly elevated in CLA treated adipocytes. Exogenous chemicals that increased endogenous ceramide levels decreased lipid levels in adipocytes, and activated AMP-activated protein kinase (AMPK) as well as NF-κB, both of which are typically activated in CLA treated adipocytes. Concurrent inhibition of ceramide de novo biosynthesis and recycling from existing sphingolipid pools attenuated the lipid lowering effect normally associated with responses to CLA, implicating ceramides as an important component of the lipid lowering response in CLA treated adipocytes. PMID:25906159

Mechanisms of Dyslipoproteinemias in Systemic Lupus Erythematosus

PubMed Central

Borba, Eduardo F.; Carvalho, Jozelio F.; Bonfá, Eloísa

2006-01-01

Autoimmunity and inflammation are associated with marked changes in lipid and lipoprotein metabolism in SLE. Autoantibodies and cytokines are able to modulate lipoprotein lipase (LPL) activity, a key enzyme in lipid metabolism, with a consequent “lupus pattern” of dyslipoproteinemia characterized by elevated levels of very low-density lipoprotein cholesterol (VLDL) and triglycerides (TG) and lower high-density lipoprotein cholesterol (HDL) levels. This pattern favors an enhanced LDL oxidation with a subsequent deleterious foam cell formation. Autoantibodies and immunocomplexes may aggravate this oxidative injury by inducing accumulation and deposition of oxLDL in endothelial cells. Drugs and associated diseases usually magnify the close interaction of these factors and further promote the proatherogenic environment of this disease. PMID:17162363

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat.

PubMed

Cho, Yun-Young; Kwon, Eun-Young; Kim, Hye-Jin; Jeon, Seon-Min; Lee, Ki-Teak; Choi, Myung-Sook

2011-01-20

Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC.

Metabolic profile of long-distance migratory flight and stopover in a shorebird.

PubMed

Landys, Meta M; Piersma, Theunis; Guglielmo, Christopher G; Jukema, Joop; Ramenofsky, Marilyn; Wingfield, John C

2005-02-07

Migrating birds often complete long non-stop flights during which body energy stores exclusively support energetic demands. The metabolic correlates of such long-distance travel in free-living migrants are as yet poorly studied. Bar-tailed godwits, Limosa lapponica taymyrensis, undertake a 4500 km flight to their single spring stopover site and thus provide an excellent model in which to determine the energy fuels associated with endurance travel. To this end, we evaluated plasma concentrations of six key metabolites in arriving godwits caught immediately upon landing near their stopover site. Initial metabolite levels were compared with levels after 5 h of inactive rest to determine how flight per se affects energy metabolism. Birds refuelling on the stopover site were also examined. Arriving godwits displayed elevated plasma free fatty acids, glycerol and butyrate, confirming the importance of lipid fuel in the support of extended migratory activity. Further-more, elevated plasma triglycerides in these birds suggest that fatty acid provisioning is facilitated through hepatic synthesis and release of neutral lipids, as previously hypothesized for small migrants with high mass-specific metabolic rates. Finally, elevations in plasma uric acid suggest that protein breakdown contributes to the support of long-distance movement, to possibly maintain citric acid cycle intermediates, gluconeogenesis and/or water balance.

Metabolic profile of long-distance migratory flight and stopover in a shorebird

PubMed Central

Landys, Mėta M.; Piersma, Theunis; Guglielmo, Christopher G.; Jukema, Joop; Ramenofsky, Marilyn; Wingfield, John C.

2005-01-01

Migrating birds often complete long non-stop flights during which body energy stores exclusively support energetic demands. The metabolic correlates of such long-distance travel in free-living migrants are as yet poorly studied. Bar-tailed godwits, Limosa lapponica taymyrensis, undertake a 4500 km flight to their single spring stopover site and thus provide an excellent model in which to determine the energy fuels associated with endurance travel. To this end, we evaluated plasma concentrations of six key metabolites in arriving godwits caught immediately upon landing near their stopover site. Initial metabolite levels were compared with levels after 5 h of inactive rest to determine how flight per se affects energy metabolism. Birds refuelling on the stopover site were also examined. Arriving godwits displayed elevated plasma free fatty acids, glycerol and butyrate, confirming the importance of lipid fuel in the support of extended migratory activity. Furthermore, elevated plasma triglycerides in these birds suggest that fatty acid provisioning is facilitated through hepatic synthesis and release of neutral lipids, as previously hypothesized for small migrants with high mass-specific metabolic rates. Finally, elevations in plasma uric acid suggest that protein breakdown contributes to the support of long-distance movement, to possibly maintain citric acid cycle intermediates, gluconeogenesis and/or water balance. PMID:15705555

Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer

PubMed Central

Swierczynski, Julian; Hebanowska, Areta; Sledzinski, Tomasz

2014-01-01

There is growing evidence that metabolic alterations play an important role in cancer development and progression. The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation. Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism. An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival, as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival. Based on the data that serum fatty acid synthase (FASN), also known as oncoantigen 519, is elevated in patients with certain types of cancer, its serum level was proposed as a marker of neoplasia. This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic neoplasm, characterized by high mortality. We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism. Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer. In particular, FASN is a viable candidate for indicator of pathologic state, marker of neoplasia, as well as, pharmacological treatment target in pancreatic cancer. Recent research showed that, in addition to lipogenesis, certain cancer cells can use fatty acids from circulation, derived from diet (chylomicrons), synthesized in liver, or released from adipose tissue for their growth. Thus, the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation. PMID:24605027

Adenovirus type 9 enhances differentiation and decreases cytokine release from preadipocytes.

PubMed

Bil-Lula, Iwona; Sochocka, Marta; Zatońska, Katarzyna; Szuba, Andrzej; Sawicki, Grzegorz; Woźniak, Mieczysław

2015-02-01

The hypothesis was that preadipocytes would have intrinsically elevated propensity to differentiate into mature adipocytes due to AdV9 infection. To test this hypothesis, the metabolic and molecular mechanisms responsible for AdV9-induced adipogenesis were examined. An association between anti-AdV9 antibodies and human obesity was also identified. 3T3L1 cells were used as a surrogate model to analyze the preadipocyte proliferation, differentiation, and maturation. An expression of E4orf1, C/EBP-β, PPAR-γ, GAPDH, aP2, LEP and fatty acid synthase gene, intracellular lipid accumulation and cytokine release were assessed. The presence of anti-AdV antibodies, serum lipids, plasma leptin, and CRP was evaluated in 204 obese and non-obese patients. AdV9-infected cells accumulated more intracellular lipids in comparison to uninfected controls. AdV9 enhanced an expression of C/EBP-β and PPAR-γ leading to an increased differentiation of preadipocytes. Overexpression of aP2 and fatty acid synthase, and decreased expression of leptin confirmed an increased accumulation of intracellular lipids due to AdV infection. Secretion of TNF-α and IL-6 from AdV9-inoculated cells was decreased strongly. About 24.5% of prevalence of anti-AdV9 antibodies was reported in the study group. AdV9-infected subjects presented higher body weights, BMIs, WHR, and central obesity. The presence of anti-AdV9 antibodies was associated with changes in serum lipids level but neither elevated CRP nor decreased leptin levels were related to obesity due to AdV infection. Data obtained from this study provide the evidences that AdV9 is a second adenovirus, which has an influence on differentiation and lipid accumulation of 3T3L1 cells. © 2014 Wiley Periodicals, Inc.

The Joint Effects of Smoking and Alcohol Drinking on Lipid-Related Indices among Chinese Males-Comparing Exercise and Non-Exercise Groups.

PubMed

Yang, Jian; Ye, Jun; Guo, Qiao; Sun, Yining; Zheng, Yansong; Zhang, Yongliang

2018-06-11

Smoking and drinking are two predisposing factors for dyslipidemia. Exercise has been proposed as a strategy to improve the blood lipids. However, it remains unclear how smoking and drinking jointly affect blood lipids and whether exercise influences their effects. To evaluate the effects of smoking and drinking, either alone or in combination, on lipid-related indices in both exercise and non-exercise groups among Chinese men. This study was conducted in a health examination center between 2015 and 2016. A sample of 6,179 male subjects was divided into exercise and non-exercise groups. Logistic and linear regression analyses were used to calculate the odds ratios for abnormal lipid-related indices and correlation coefficients between smoking/drinking and lipid-related indices. In the study population, the percentage of stable smokers and stable drinkers was 46.3% (2,860/6,179) and 77.6% (4,795/6,179), respectively. An increased smoking amount was significantly associated with an elevated triglyceride (TG) level and a decreased high-density lipoprotein cholesterol (HDL-C) level. Heavier smokers had higher odds ratios for high TG and low HDL-C. Heavier drinkers had higher levels of total cholesterol (TC), TG, and HDL-C and higher odds ratios for high TC and high TG but lower odds ratio for low HDL-C. The exercise group had lower TG levels and higher HDL-C levels than did the non-exercise group. Both heavier smoking and heavier drinking were associated with poorer TG levels, and the results suggest that drinking may be helpful for HDL-C. Exercise may relieve the negative effects of smoking and drinking.

Hawthorn Fruit Extract Elevates Expression of Nrf2/HO-1 and Improves Lipid Profiles in Ovariectomized Rats

PubMed Central

Yoo, Jeong-Hyun; Liu, Yanan; Kim, Hyun-Sook

2016-01-01

The purpose of this study was to investigate the effects of hawthorn (Crataegus pinnatifida Bunge) extract on the lipid profiles and antioxidant properties in ovariectomized (OVX) rats. After ovariectomy, the rats were randomly divided into four groups: the non-OVX control (Sham), the OVX-control (OVX), the OVX + 100 mg/kg b.w. of hawthorn extract (OL), and the OVX + 200 mg/kg b.w. of hawthorn extract (OH). The final body weights of the OVX group were significantly increased, but the increment was significantly decreased in hawthorn groups (p < 0.05). The serum total and low-density lipoprotein (LDL) cholesterol levels were significantly elevated in the OVX group, whereas the hawthorn groups showed a significant decrease in these levels (p < 0.05). The hepatic triglyceride (TG) and malondialdehyde (MDA) levels were significantly reduced in the hawthorn groups compared with the OVX group (p < 0.05). The mRNA expression of nuclear factor erythroid 2–related factor (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase (GPx) were significantly decreased in the OVX group, whereas the hawthorn groups exhibited a significant increase in expression (p < 0.05). The protein expressions of Nrf2, HO-1, and GPx were lower in the OVX group than the Sham group (p < 0.05). The oral administration of hawthorn extract reversed the suppression of protein levels. These results suggest that hawthorn extract could have protective effects in OVX rats by improving lipid profiles, decreasing oxidative stress, and improving the antioxidant defense system. PMID:27187458

Hawthorn Fruit Extract Elevates Expression of Nrf2/HO-1 and Improves Lipid Profiles in Ovariectomized Rats.

PubMed

Yoo, Jeong-Hyun; Liu, Yanan; Kim, Hyun-Sook

2016-05-13

The purpose of this study was to investigate the effects of hawthorn (Crataegus pinnatifida Bunge) extract on the lipid profiles and antioxidant properties in ovariectomized (OVX) rats. After ovariectomy, the rats were randomly divided into four groups: the non-OVX control (Sham), the OVX-control (OVX), the OVX + 100 mg/kg b.w. of hawthorn extract (OL), and the OVX + 200 mg/kg b.w. of hawthorn extract (OH). The final body weights of the OVX group were significantly increased, but the increment was significantly decreased in hawthorn groups (p < 0.05). The serum total and low-density lipoprotein (LDL) cholesterol levels were significantly elevated in the OVX group, whereas the hawthorn groups showed a significant decrease in these levels (p < 0.05). The hepatic triglyceride (TG) and malondialdehyde (MDA) levels were significantly reduced in the hawthorn groups compared with the OVX group (p < 0.05). The mRNA expression of nuclear factor erythroid 2-related factor (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase (GPx) were significantly decreased in the OVX group, whereas the hawthorn groups exhibited a significant increase in expression (p < 0.05). The protein expressions of Nrf2, HO-1, and GPx were lower in the OVX group than the Sham group (p < 0.05). The oral administration of hawthorn extract reversed the suppression of protein levels. These results suggest that hawthorn extract could have protective effects in OVX rats by improving lipid profiles, decreasing oxidative stress, and improving the antioxidant defense system.

The Associations of Serum Lipids with Vitamin D Status.

PubMed

Wang, Ying; Si, Shaoyan; Liu, Junli; Wang, Zongye; Jia, Haiying; Feng, Kai; Sun, Lili; Song, Shu Jun

2016-01-01

Vitamin D deficiency has been associated with some disorders including cardiovascular diseases. Dyslipidemia is a major risk factor for cardiovascular diseases. However, data about the relationships between vitamin D and lipids are inconsistent. The relationship of vitamin D and Atherogenic Index of Plasma (AIP), as an excellent predictor of level of small and dense LDL, has not been reported. The objective of this study was to investigate the effects of vitamin D status on serum lipids in Chinese adults. The study was carried out using 1475 participants from the Center for Physical Examination, 306 Hospital of PLA in Beijing, China. Fasting blood samples were collected and serum concentrations of 25(OH)D, total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were measured. AIP was calculated based on the formula: log [TG/HDL-C]. Multiple linear regression analysis was used to estimate the associations between serum 25(OH)D and lipids. The association between the occurrences of dyslipidemias and vitamin D levels was assessed by multiple logistic regression analysis. Confounding factors, age and BMI, were used for the adjustment. The median of serum 25(OH)D concentration was 47 (27-92.25) nmol/L in all subjects. The overall percentage of 25(OH)D ≦ 50 nmol/L was 58.5% (males 54.4%, females 63.7%). The serum 25(OH)D levels were inversely associated with TG (β coefficient = -0.24, p < 0.001) and LDL-C (β coefficient = -0.34, p < 0.001) and positively associated with TC (β coefficient = 0.35, p < 0.002) in men. The associations between serum 25(OH)D and LDL-C (β coefficient = -0.25, p = 0.01) and TC (β coefficient = 0.39, p = 0.001) also existed in women. The serum 25(OH)D concentrations were negatively associated with AIP in men (r = -0.111, p < 0.01) but not in women. In addition, vitamin D deficient men had higher AIP values than vitamin D sufficient men. Furthermore, the occurrences of dyslipidemias (reduced HDL-C, elevated TG and elevated AIP) correlated with lower 25(OH)D levels in men, whereas the higher TC and LDL-C associated with higher 25(OH)D levels in women. It seems that the serum 25(OH)D levels are closely associated with the serum lipids and AIP. Vitamin D deficiency may be associated with the increased risk of dyslipidemias, especially in men. The association between vitamin D status and serum lipids may differ by genders.

Spontaneous nonalcoholic fatty liver disease and ER stress in Sidt2 deficiency mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Jialin; Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu, 241001; Zhang, Yao

Sidt2 is a newly discovered lysosomal membrane protein that is closely related to glucose metabolism. In the present study, we found that Sidt2 is also closely related to lipid metabolism. Gradual increases in serum triglyceride (TG) and free fatty acid, as well as elevated aspartate transaminase and alanine transaminase levels were observed in Sidt2{sup −/−} mice fed a normal diet from the age of 3 months, suggesting the presence of lipid metabolism disorders and impaired liver function in these mice. In the liver slices of 6-month-old Sidt2{sup −/−} mice, there were obvious fat degeneration and inflammatory changes. Almost all ofmore » the liver cells demonstrated different levels of lipid droplet accumulation and cell swelling, and some of the cells demonstrated balloon-like changes. Infiltration of inflammatory cells was observed in the portal area and hepatic lobule. Electron microscopy showed that macrophages tended to be attached to the endothelial cells, and a large number of lipid droplets were present in the liver cells. Oil red O staining showed that there were significantly increased number of deep straining particles in the liver cells of Sidt2{sup −/−} mice, and the TG content in liver tissue was also significantly increased. Detection of key genes and proteins related to fat synthesis showed that mRNA and protein levels of the SREBP1c in the liver of Sidt2{sup −/−} mice were significantly elevated, and the downstream genes acetyl-CoA carboxylase, fatty acid synthase, and mitochondrial glycerol 3-phosphate acyltransferase were significantly upregulated. In addition, there was severe endoplasmic reticulum stress (ERS) in the liver of Sidt2{sup −/−} mice, which had significantly increased levels of markers specific for unfolded protein response activation, Grp78 and CHOP, as well as significant elevation of downstream p-PERK, p-eIF2a, p-IRE1a, along with ER damage. These results suggest that Sidt2{sup −/−} mice had spontaneous nonalcoholic fatty liver disease (NAFLD) accompanied by ERS. In summary, as a lysosomal membrane protein, Sidt2 plays an important role in the pathogenesis of NAFLD, and ERS may mediate the occurrence and development of this disease in Sdit2 deficiency mice.« less

The Association between genetic variations of CHI3L1, levels of the encoded glycoprotein YKL-40 and the lipid profile in a Danish population.

PubMed

Thomsen, Stine Brinkløv; Rathcke, Camilla Noelle; Skaaby, Tea; Linneberg, Allan; Vestergaard, Henrik

2012-01-01

The inflammatory biomarker YKL-40 seems to play a role in atherosclerosis and is elevated in patients with obesity, cardiovascular disease and type 2 diabetes. Single nucleotide polymorphisms (SNPs) of the YKL-40 encoding gene, CHI3L1, are associated with inter-individual YKL-40 levels. One study has described an association between a promoter polymorphism of CHI3L1 and levels of low density lipoprotein. The objective of this study was to evaluate the influence of YKL-40 on lipid parameters by determining the association between polymorphisms of CHI3L1, serum YKL-40 and levels of the differentiated lipid profile in a Danish general population. 12 SNPs of CHI3L1 were genotyped, and serum YKL-40 and parameters of the lipid profile were measured in 2,656 Danes. Lipid profile and genotypes were available in another Danish population (n = 6,784) for replication. Cholesterol and triglyceride levels increased with increasing YKL-40 quartile (both p<0.0001), and YKL-40 correlated with triglyceride levels (β = 0.15, p<0.0001). Low density lipoprotein levels increased slightly from the 1(st) to the 3(rd) quartile (p = 0.006). The highest YKL-40 quartile was associated with a greater risk of hypercholesterolemia compared to the lowest YKL-40 quartile (odds ratio 1.36, p = 0.009). Minor homozygosity of rs12123883 was associated with higher triglyceride levels (p = 0.022) and a higher prevalence of low high density lipoprotein (p = 0.012), but these associations could not be confirmed in the replication population. Serum YKL-40 correlates with triglyceride levels in a representative group of the general Danish population. No consistent associations between SNPs of CHI3L1 and lipid levels could be documented.

Lipid peroxidative damage in the erythrocytes and elevation of serum LDL-cholesterol, apolipoprotein-B, ferritin and uric acid with age and in coronary heart disease patients.

PubMed

El-Gebali, H H; Tahir, S A; Haider, S S; El-Fakhri, M M

2000-02-01

To determine the normal serum levels of LDL-cholesterol, apolipoprotein-B, ferritin, uric acid, and the extent of erythrocytes lipid peroxidation in healthy control group subjects and to compare them with coronary heart disease patients. Secondly, to study the effects of age and sex on these parameters. The blood samples from 150 healthy Libyan control group subjects (110 men and 40 women) were classified into 3 groups according to their age. Group I consisted of 76 subjects with an age range from 20 to 35 years. Group II consisted of 45 subjects with an age range from 36 to 50 years. Group III consisted of 29 subjects with an age range from 51 to 74 years. The blood samples from these groups were analyzed for LDL-cholesterol, apolipoprotein-B, ferritin and uric acid levels. Lipid peroxidation was compared in the erythrocytes of 56 selected healthy control group subjects (31 men and 11 women) of the aforementioned age groups. These parameters have shown age-dependent elevation in their levels. Meanwhile, LDL-cholesterol and Apolipoprotein-B levels in female subjects were higher than those of males. However, lipid peroxidation in the erythrocytes has revealed a statistically significant increase with increasing age. The comparison between 93 selected, sex and age matched, healthy control group subjects with 87 selected coronary heart disease patients (55 men and 45 women) with an age range from 30 to 74 years (49.6+13.25) has demonstrated significantly higher concentration of LDL-cholesterol, Apolipoprotein-B, ferritin and uric acid in coronary heart disease patients than those of healthy control group subjects. Meanwhile, lipid peroxidation was also significantly enhanced in coronary heart disease patients compared with healthy control group subjects. Our study has revealed that an increase in the lipid peroxidation in erythrocytes with age and during coronary heart disease, makes red cell membranes more vulnerable to free radical damage via formation of reactive oxygen species. It is thus likely that peroxidative damage may be contributing to an increase in serum LDL-cholesterol, Apolipoprotein-B, probably after its oxidative modification, increase in ferritin and hyperuricemia in coronary heart disease patients.

Impact of currently prescribed lipid-lowering drugs on plasma PCSK9 concentration: single or in combination study in rats

PubMed Central

2014-01-01

Background An emerging data suggested a significant impact of statins on PCSK9 concentration, while the rapid impacts of other lipid-lowering drugs such as ezetimibe and xuezhikang alone or in combination on PCSK9 and lipid profile have not been assessed. This study aims to investigate whether an enhanced PCSK9 concentration by single or combined therapy of lipid-lowering drugs currently used precedes the changes of lipid profile in rats. Methods Sixty-three rats were randomly divided into six groups and orally administrated with placebo (N = 13), ezetimibe 10 mg/kg daily, Xuezhikang 1200 mg/kg daily, ezetimibe 10 mg/kg plus Xuezhikang 1200 mg/kg daily, pitavastatin 10 mg/kg daily or pitavastatin 10 mg/kg plus ezetimibe 10 mg/kg daily for 3 days (N = 10 for each group respectively). Blood samples were obtained at day 3 after orally administration. Plasma PCSK9 levels were determined by ELISA and lipid profile were measured by enzymatic assay. Results Ezetimibe, Xuezhikang and pitavastatin alone and Xuezhikang plus ezetimibe as well as pitavastatin plus ezetimibe increased PCSK9 levels by 124%, 56%, 111%, 63% and 204% respectively (p < 0.05 compared with placebo). However, Xuezhikang plus ezetimibe did not enhance greater PCSK9 levels compared to monotherapy. Ezetimibe and pitavastatin in combination induced higher PCSK9 levels than pitavastatin monotherapy or co-therapy with ezetimibe plus Xuezhikang. There was no significant difference between any groups with regard to lipid profile levels at day 3 (P > 0.05). Conclusions Elevated PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was found prior to the alterations of lipid profile in rats. Combination of Xuezhikang and ezetimibe significantly attenuated increase in PCSK9 compared to ezetimibe plus pitavastatin, suggesting that the former combination may be better than the latter in future clinical application. PMID:24533584

Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis.

PubMed

Zhou, Richard; Lin, Jianjun; Wu, Defeng

2014-01-01

The mechanism(s) by which alcohol causes cell injury are still not clear but a major mechanism appears to be the role of lipid peroxidation and oxidative stress in alcohol toxicity. CYP2E1-generated ROS contributes to the ethanol-induced oxidant stress and inhibition of CYP2E1 activity decreases ethanol-induced fatty liver. The transcription factor Nrf2 regulates the expression of many cytoprotective enzymes which results in cellular protection against a variety of toxins. The current study was designed to evaluate the ability of sulforaphane, an activator of Nrf2, to blunt CYP2E1-dependent, ethanol-induced steatosis in vivo and in vitro. The sulforaphane treatment activated Nrf2, increased levels of the Nrf2 target heme oxygenase-1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-nitrotyrosine protein adducts and an increase in GSH levels after the acute ethanol treatment. It decreased ethanol-elevated liver levels of triglycerides and cholesterol and Oil Red O staining. Similar results were found in vitro as addition of sulforaphane to HepG2 E47 cells, which express CYP2E1, elevated Nrf2 levels and decreased the accumulation of lipid in cells cultured with ethanol. Sulforaphane treatment had no effect on levels of or activity of CYP2E1. Sulforaphane proved to be an effective in vivo inhibitor of acute ethanol-induced fatty liver in mice. The possible amelioration of liver injury which occurs under these conditions by chemical activators of Nrf2 is of clinical relevance and worthy of further study. © 2013.

Sulforaphane Induces Nrf2 and Protects Against CYP2E1-dependent Binge Alcohol –induced Liver Steatosis

PubMed Central

Zhou, Richard; Lin, Jianjun; Wu, Defeng

2013-01-01

Background The mechanism(s) by which alcohol causes cell injury are still not clear but a major mechanism appears to be the role of lipid peroxidation and oxidative stress in alcohol toxicity. CYP2E1-generated ROS contributes to the ethanol-induced oxidant stress and inhibition of CYP2E1 activity decreases ethanol-induced fatty liver. The transcription factor Nrf2 regulates the expression of many cytoprotective enzymes which results in cellular protection against a variety of toxins. Method The current study was designed to evaluate the ability of sulforaphane, an activator of Nrf2, to blunt CYP2E1-dependent, ethanol-induced steatosis in vivo and in vitro. Results The sulforaphane treatment activated Nrf2, increased levels of the Nrf2 target heme oxygenase -1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-Nitrotyrosine protein adducts and an increase in GSH levels after the acute ethanol treatment. It decreased ethanol-elevated liver levels of triglycerides and cholesterol and Oil Red O staining. Similar results were found in vitro as addition of sulforaphane to HepG2 E47 cells, which express CYP2E1, elevated Nrf2 levels and decreased the accumulation of lipid in cells cultured with ethanol. Sulforaphane treatment had no effect on levels of or activity of CYP2E1. Conclusions Sulforaphane proved to be an effective in vivo inhibitor of acute ethanol–induced fatty liver in mice. General significance The possible amelioration of liver injury which occurs under these conditions by chemical activators of Nrf2 is of clinical relevance and worthy of further study. PMID:24060752

Lower Serum Testosterone Associated with Elevated Polychlorinated Biphenyl Concentrations in Native American Men

PubMed Central

Goncharov, Alexey; Rej, Robert; Negoita, Serban; Schymura, Maria; Santiago-Rivera, Azara; Morse, Gayle; Carpenter, David O.

2009-01-01

Background Polychlorinated biphenyls (PCBs) and chlorinated pesticides are endocrine disruptors, altering both thyroid and estrogen hormonal systems. Less is known of action on androgenic systems. Objective We studied the relationship between serum concentrations of testosterone in relation to levels of PCBs and three chlorinated pesticides in an adult Native American (Mohawk) population. Methods We collected fasting serum samples from 703 adult Mohawks (257 men and 436 women) and analyzed samples for 101 PCB congeners, hexachlorobenzene (HCB), dichlorodiphenyldichloroethylene (DDE), and mirex, as well as testosterone, cholesterol, and triglycerides. The associations between testosterone and tertiles of serum organochlorine levels (both wet weight and lipid adjusted) were assessed using a logistic regression model while controlling for age, body mass index (BMI), and other analytes, with the lowest tertile being considered the referent. Males and females were considered separately. Results Testosterone concentrations in males were inversely correlated with total PCB concentration, whether using wet-weight or lipid-adjusted values. The odds ratio (OR) of having a testosterone concentration above the median was 0.17 [95% confidence interval (CI), 0.05–0.69] for total wet-weight PCBs (highest vs. lowest tertile) after adjustment for age, BMI, total serum lipids, and three pesticides. The OR for lipid-adjusted total PCB concentration was 0.23 (95% CI, 0.06–0.78) after adjustment for other analytes. Testosterone levels were significantly and inversely related to concentrations of PCBs 74, 99, 153, and 206, but not PCBs 52, 105, 118, 138, 170, 180, 201, or 203. Testosterone concentrations in females are much lower than in males, and not significantly related to serum PCBs. HCB, DDE, and mirex were not associated with testosterone concentration in either men or women. Conclusions Elevation in serum PCB levels is associated with a lower concentration of serum testosterone in Native American men. PMID:19750113

The possible contribution of a general glycosphingolipid transporter, GM2 activator protein, to atherosclerosis.

PubMed

Yanai, Hidekatsu; Yoshida, Hiroshi; Tomono, Yoshiharu; Tada, Norio; Chiba, Hitoshi

2006-12-01

We previously found that oxidized low-density lipoprotein (LDL) elevated the expression of mRNA of GalNAcbeta1-4[NeuNAcalpha2-3]Galbeta1-4Glc-Cer (GM2) ganglioside activator protein, in human monocyte-derived macrophages. Recently, GM2 activator protein has become known as a general glycosphingolipid transporter as well as a specific cofactor for the hydrolysis of GM2 ganglioside by lysosomal beta-hexosaminidase A. Accumulation of glycosphingolipids has been observed in the serum or aorta of atherosclerotic model animals and humans. The proliferation of aortic smooth muscle cells, elevation of LDL uptake by macrophages, interfering LDL clearance by the liver, and enhancement of platelet adhesion to collagen have been proposed as the underlying mechanisms of glycosphingolipid-mediated atherogenesis. The GM2 activator protein can bind, solubilize and transport a broad spectrum of lipid molecules, indicating that GM2 activator protein may function as a general intra- and inter-cellular lipid transport protein. Collectively, elevated levels of GM2 activator protein in the aorta may be another feature of human atherosclerosis.

Quantitative trait loci at the 11q23.3 chromosomal region related to dyslipidemia in the population of Andhra Pradesh, India.

PubMed

Pranavchand, Rayabarapu; Reddy, Battini Mohan

2017-06-13

Given the characteristic atherogenic dyslipidemia of south Indian population and crucial role of APOA1, APOC3, APOA4 and APOA5 genes clustered in 11q23.3 chromosomal region in regulating lipoprotein metabolism and cholesterol homeostasis, a large number of recently identified variants are to be explored for their role in regulating the serum lipid parameters among south Indians. Using fluidigm SNP genotyping platform, a prioritized set of 96 SNPs of the 11q23.3 chromosomal region were genotyped on 516 individuals from Hyderabad, India, and its vicinity and aged >45 years. The linear regression analysis of the individual lipid traits viz., TC, LDLC, HDLC, VLDL and TG with each of the 78 SNPs that confirm to HWE and with minor allele frequency > 1%, suggests 23 of those to be significantly associated (p ≤ 0.05) with at least one of these quantitative traits. Most importantly, the variant rs632153 is involved in elevating TC, LDLC, TG and VLDLs and probably playing a crucial role in the manifestation of dyslipidemia. Additionally, another three SNPs rs633389, rs2187126 and rs1263163 are found risk conferring to dyslipidemia by elevating LDLC and TC levels in the present population. Further, the ROC (receiver operating curve) analysis for the risk scores and dyslipidemia status yielded a significant area under curve (AUC) = 0.675, suggesting high discriminative power of the risk variants towards the condition. The interaction analysis suggests rs10488699-rs2187126 pair of the BUD13 gene to confer significant risk (Interaction odds ratio = 14.38, P = 7.17 × 10 5 ) towards dyslipidemia by elevating the TC levels (β = 37.13, p = 6.614 × 10 5 ). On the other hand, the interaction between variants of APOA1 gene and BUD13 and/or ZPR1 regulatory genes at this region are associated with elevated TG and VLDL. The variants at 11q23.3 chromosomal region seem to determine the quantitative lipid traits and in turn dyslipidemia in the population of Hyderabad. Particularly, the variants rs632153, rs633389, rs2187126 and rs1263163 might be risk conferring to dyslipidemia by elevating LDLC and TC levels, while the variants of APOC3 and APOA1 genes might be the genetic determinants of elevated triglycerides in the present population.

Increased breath ethane levels in medicated patients with schizophrenia and bipolar disorder are unrelated to erythrocyte omega-3 fatty acid abundance.

PubMed

Ross, Brian M; Maxwell, Ross; Glen, Iain

2011-03-30

Oxidative stress has been reported to be elevated in mental illness. Preliminary evidence suggests this phenomenon can be assessed non-invasively by determining breath levels of the omega-3 polyunsaturated fatty acid (PUFA) oxidation product ethane. This study compares alkane levels in chronic, medicated, patients with schizophrenia or bipolar disorder with those in healthy controls. Both ethane and butane levels were significantly increased in patients with schizophrenia or bipolar disorder, although elevated butane levels were likely due to increased ambient gas concentrations. Ethane levels were not correlated with symptom severity or with erythrocyte omega-3 PUFA levels. Our results support the hypothesis that oxidative stress is elevated in patients with schizophrenia and bipolar disorder leading to increased breath ethane abundance. This does not appear to be caused by increased abundance of omega-3 PUFA, but rather is likely due to enhanced oxidative damage of these lipids. As such, breath hydrocarbon analysis may represent a simple, non-invasive means to monitor the metabolic processes occurring in these disorders. Copyright © 2010 Elsevier Inc. All rights reserved.

Adverse lipid profile elevates risk for subarachnoid hemorrhage: A prospective population-based cohort study.

PubMed

Lindbohm, Joni; Korja, Miikka; Jousilahti, Pekka; Salomaa, Veikko; Kaprio, Jaakko

2018-05-05

Studies report that both high and low total cholesterol (TC) elevates SAH risk. There are few prospective studies on high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C), and apparently none concerns apolipoproteins A and B. We aimed to clarify the association between lipid profile and SAH risk. The National FINRISK study provided risk-factor data recorded at enrolment between 1972 and 2007. During 1.52 million person-years of follow-up until 2014, 543 individuals suffered from incident hospitalized SAH or outside-hospital-fatal SAH. Cox proportional hazards model was used to calculate the hazard ratios and multiple imputation predicted ApoA1, ApoB, and LDL-C values for cohorts from a time before apolipoprotein-measurement methods were available. One SD elevation (1.28 mmol/l) in TC elevated SAH risk in men (hazard ratio (HR) 1.15 (95% CIs 1.00-1.32)). Low HDL-C levels increased SAH risk, as each SD decrease (0.37 mmol/l) in HDL-C raised the risk in women (HR 1.29 (95% CIs 1.07-1.55)) and men (HR 1.20 (95% CIs 1.14-1.27)). Each SD increase (0.29 g/l) in ApoA1 decreased SAH risk in women (HR 0.85 (95% CIs 0.74-0.97)) and men (HR 0.88 (95% CIs 0.76-1.02)). LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l) elevated SAH risk in men with HR 1.15 (95% CIs 1.01-1.31) and HR 1.26 (95% CIs 1.10-1.44) per one SD increase. Age did not change these findings. An adverse lipid profile seems to elevate SAH risk similar to its effect in other cardiovascular diseases, especially in men. Whether SAH incidence diminishes with increasing statin use remains to be studied. Copyright © 2018 Elsevier B.V. All rights reserved.

Vitamin E and vitamin E-quinone levels in red blood cells and plasma of newborn infants and their mothers.

PubMed

Jain, S K; Wise, R; Bocchini, J J

1996-02-01

Vitamin E is a physiological antioxidant and protects cell membranes from oxidative damage. This study has determined whether vitamin E level in RBC of newborns has any relationship with its level in their mothers. We have also examined levels of vitamin E and vitamin E-quinone, an oxidized product of vitamin E, in paired samples of red blood cells (RBC) and plasma of newborns and their mothers. Blood was collected from 26 mothers and their full-term placental cords at delivery. Vitamin E and vitamin E-quinone levels were determined in RBC and plasma by HPLC. Newborn-plasma had significantly lower vitamin E levels compared with maternal-plasma both when expressed as nmole/ml (5.5+/-0.4 vs 26.1+/-1.1, p = 0.0001) or nmole/mumole total lipids (1.9+/-0.1 vs 2.6+/-0.1, p = 0.0001). Vitamin E level in the newborn-RBC was similar to that of maternal-RBC when expressed as nmole/ml packed cells (2.77+/-0.14 vs 2.95+/-0.13), but was significantly lower when expressed as nmole/mumole total lipids (0.56+/-0.03 vs 0.64+/-0.04, p = 0.03) from that of maternal-RBC. Vitamin E-quinone levels are significantly elevated in newborns compared with their mothers both in RBC (29.4+/-2.1 vs 24.1+/-1.2, p = 0.04) and plasma (39.9+/-5.3 vs 25.3+/-4.2, p = 0.006) when expressed as nmole/mmole total lipids but not when expressed as nmole/ml. There was a significant correlation of vitamin E between newborn-plasma and newborn-RBC (r = 0.65, p = 0.0002 for nmole per ml packed RBC;r = 0.63, p = 0.0007 for nmole per mumole total lipids). The relationship between maternal plasma and newborn plasma was significant when vitamin E was normalized with nmole/mumole total lipid (r = 0.54, p = 0.007 but not when expressed as nmole/ml (r = 0.09, p = 0.64). However, vitamin E in the RBC of maternal and newborn had significant correlation when expressed as per ml packed cells (r = 0.61, p = 0.001) and per total lipid (r = 0.46, p = 0.02). There was no relationship of vitamin E-quinone levels between RBC and plasma of newborns and their mothers. Elevated blood levels of vitamin E-quinone suggest increased oxidative stress and utilization of vitamin E in newborns compared to their mothers. Because vitamin E levels in RBC of newborns are lower and significantly related to vitamin E levels in RBC of their mothers, an increase in vitamin E supplementation to mothers during pregnancy may increase vitamin E levels in the newborn and help impede the effect of extrauterine oxygen toxicity.

Hepatic lipidosis in pregnant captive American bison (Bison bison).

PubMed

Palmer, Mitchell V; Olsen, Steve C

2002-11-01

Hepatic lipidosis, a hallmark lesion of lipid mobilization disorders in ruminants, was noted in four 3-year-old, pregnant bison (Bison bison) after periods of anorexia that progressed to recumbency and death. The affected bison were part of a herd at the National Animal Disease Center (NADC) that was used for brucellosis vaccine research. Microscopically, the liver contained swollen hepatocytes with numerous, variably sized, round, smoothly contoured vacuoles that displaced cytoplasmic structures. Hepatocytes in all zones of the lobule were affected equally. Hypoglycemia, decreased total carbon dioxide, elevated gamma-glutamyltransferase, elevated alkaline phosphatase, and increased nonesterified fatty acid levels were noted. As in the case of cattle, altered nutritional demands of late gestation combined with management factors such as obesity, nutrition, stress, and concomitant disease may be critical in the pathophysiology of lipid mobilization disorders in bison. Additionally, stressors unique to this research herd likely contributed to fatal hepatic lipidosis.

Elevated serum β₂-GPI-Lp(a) complexes levels in children with nephrotic syndrome.

PubMed

Zhang, Chunni; Luo, Yang; Huang, Zhongwei; Xia, Zhengkun; Cai, Xiaoyi; Yang, Yuhua; Niu, Dongmei; Wang, Junjun

2012-10-09

The complexes of β₂-glycoprotein I (β₂-GPI) with lipoprotein(a) [β₂-GPI-Lp(a)] exist in human circulation and are increased in serum from patients with some autoimmune diseases. This study aims to investigate the concentration of β₂-GPI-Lp(a) in serum of children with idiopathic nephrotic syndrome (NS) and its relationship with serum lipids, oxidized lipoprotein and renal function parameters to explore the potential of the complexes as an additional marker for evaluating pediatric NS. Serum concentrations of β₂-GPI-Lp(a) complexes and oxidized Lp(a) [ox-Lp(a)] were measured by "Sandwich" ELISAs in 80 NS children and 82 age/sex-matched healthy controls. The levels of serum lipids and kidney parameters were also determined. Multivariate logistic regression analysis was performed to identify correlate of β₂-GPI-Lp(a) and NS. The serum concentrations of β₂-GPI-Lp(a) complexes in children with NS were significantly higher than those in controls (median 0.95 U/ml vs 0.28 U/ml, P<0.0001). Ox-Lp(a) levels were also markedly elevated (median 14.55 mg/l vs 2.60 mg/l, P<0.0001] in NS children. The concentrations of β₂-GPI-Lp(a) were positively correlated with ox-Lp(a) (r=0.246, P=0.028), but not with Lp(a) level, and the concentrations of ox-Lp(a) were positively related with Lp(a) (r=0.301, P=0.007) in NS children. Multivariate logistic regression analysis identified a positive association between NS and β₂-GPI-Lp(a) (OR=13.694, 95% CI 6.400-29.299, P<0.0001), after adjusting for kidney function parameters, serum lipids and ox-Lp(a). Elevated β₂-GPI-Lp(a) level was an independent and significant risk factor for pediatric NS and, enhanced Lp(a) oxidation partly contributes to the formation of β₂-GPI-Lp(a) complexes. Copyright © 2012 Elsevier B.V. All rights reserved.

Subchronic cadmium exposure upregulates the mRNA level of genes associated to hepatic lipid metabolism in adult female CD1 mice.

PubMed

Zhang, Jun; Wang, Yan; Fu, Lin; Feng, Yu-Jie; Ji, Yan-Li; Wang, Hua; Xu, De-Xiang

2018-07-01

Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in humans and shows adverse effects on health. Accumulating evidence reveals that environmental Cd exposure is associated with hepatic lipid accumulation and metabolic alterations in adult male mice. However, whether Cd exposure induces hepatic lipid accumulation and metabolic alterations in female mice remains poorly understood. In the present study, we aimed to investigate the effects of Cd exposure on insulin resistance, hepatic lipid accumulation and associated metabolic pathways. Female CD1 mice were administrated with CdCl 2 (10 and 100 mg l -1 ) by drinking water. We found that Cd exposure did not induce obesity, insulin resistance and hepatic lipid accumulation. By contrary, mice in the Cd-100 mg l -1 group presented a significant reduction of the glucose area under the curve during the glucose tolerance test. However, there was a significant elevation in the mRNA level of Fasn and Scd-1, which were critical genes during hepatic fatty acid synthesis. Moreover, hepatic Fabp1 and Fabp4, two genes for hepatic fatty acid uptake were upregulated in Cd-treated mice. Of interest, Lpl, a key gene for hepatic lipoprotein lysis, was also upregulated in Cd-treated mice. Collectively, our results suggest that Cd exposure upregulated mRNA level of genes related to hepatic lipid metabolism although there was no insulin resistance and hepatic lipid accumulation shown in the present study. Copyright © 2018 John Wiley & Sons, Ltd.

Chemotherapy Agents Alter Plasma Lipids in Breast Cancer Patients and Show Differential Effects on Lipid Metabolism Genes in Liver Cells.

PubMed

Sharma, Monika; Tuaine, Jo; McLaren, Blair; Waters, Debra L; Black, Katherine; Jones, Lynnette M; McCormick, Sally P A

2016-01-01

Cardiovascular complications have emerged as a major concern for cancer patients. Many chemotherapy agents are cardiotoxic and some appear to also alter lipid profiles, although the mechanism for this is unknown. We studied plasma lipid levels in 12 breast cancer patients throughout their chemotherapy. Patients received either four cycles of doxorubicin and cyclophosphamide followed by weekly paclitaxel or three cycles of epirubicin, cyclophosphamide and 5'-fluorouracil followed by three cycles of docetaxel. Patients demonstrated a significant reduction (0.32 mmol/L) in high density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1) levels (0.18 g/L) and an elevation in apolipoprotein B (apoB) levels (0.15 g/L) after treatment. Investigation of the individual chemotherapy agents for their effect on genes involved in lipoprotein metabolism in liver cells showed that doxorubicin decreased ATP binding cassette transporter A1 (ABCA1) via a downregulation of the peroxisomal proliferator activated receptor γ (PPARγ) and liver X receptor α (LXRα) transcription factors. In contrast, ABCA1 levels were not affected by cyclophosphamide or paclitaxel. Likewise, apoA1 levels were reduced by doxorubicin and remained unaffected by cyclophosphamide and paclitaxel. Doxorubicin and paclitaxel both increased apoB protein levels and paclitaxel also decreased low density lipoprotein receptor (LDLR) protein levels. These findings correlate with the observed reduction in HDL-C and apoA1 and increase in apoB levels seen in these patients. The unfavourable lipid profiles produced by some chemotherapy agents may be detrimental in the longer term to cancer patients, especially those already at risk of cardiovascular disease (CVD). This knowledge may be useful in tailoring effective follow-up care plans for cancer survivors.

Treating elevated cholesterol levels: the great Satan in perspective.

PubMed

Gibaldi, M; Kradjan, W

1996-03-01

The purpose of this review is to provide perspective on the developments leading to the recognition of high cholesterol levels as a risk factor for coronary heart disease (CHD). Another objective is to consider the unfolding controversies regarding the relative value of cholesterol-lowering drug therapy in primary and secondary prevention. Should physicians use lipid-lowering drugs to treat patients with elevated cholesterol levels but no clinical evidence of coronary disease, or limit intervention to patients with a previous history of angina, coronary angioplasty, coronary artery bypass surgery, or myocardial infarction? This review finds inadequate data to support a recommendation for screening large populations for the presence of elevated cholesterol levels or for primary prevention in those known to have high cholesterol. On the other hand, there is mounting evidence to support vigorous intervention in those with known coronary disease. Further study is needed to determine whether a subset of patients with one or more well-defined risk factors would benefit from primary prevention.

Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

PubMed Central

Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

2013-01-01

Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

Ambient Ultrafine Particle Ingestion Alters Gut Microbiota in Association with Increased Atherogenic Lipid Metabolites

PubMed Central

Li, Rongsong; Yang, Jieping; Saffari, Arian; Jacobs, Jonathan; Baek, Kyung In; Hough, Greg; Larauche, Muriel H.; Ma, Jianguo; Jen, Nelson; Moussaoui, Nabila; Zhou, Bill; Kang, Hanul; Reddy, Srinivasa; Henning, Susanne M.; Campen, Matthew J.; Pisegna, Joseph; Li, Zhaoping; Fogelman, Alan M.; Sioutas, Constantinos; Navab, Mohamad; Hsiai, Tzung K.

2017-01-01

Ambient particulate matter (PM) exposure is associated with atherosclerosis and inflammatory bowel disease. Ultrafine particles (UFP, dp < 0.1–0.2 μm) are redox active components of PM. We hypothesized that orally ingested UFP promoted atherogenic lipid metabolites in both the intestine and plasma via altered gut microbiota composition. Low density lipoprotein receptor-null (Ldlr−/−) mice on a high-fat diet were orally administered with vehicle control or UFP (40 μg/mouse/day) for 3 days a week. After 10 weeks, UFP ingested mice developed macrophage and neutrophil infiltration in the intestinal villi, accompanied by elevated cholesterol but reduced coprostanol levels in the cecum, as well as elevated atherogenic lysophosphatidylcholine (LPC 18:1) and lysophosphatidic acids (LPAs) in the intestine and plasma. At the phylum level, Principle Component Analysis revealed significant segregation of microbiota compositions which was validated by Beta diversity analysis. UFP-exposed mice developed increased abundance in Verrocomicrobia but decreased Actinobacteria, Cyanobacteria, and Firmicutes as well as a reduced diversity in microbiome. Spearman’s analysis negatively correlated Actinobacteria with cecal cholesterol, intestinal and plasma LPC18:1, and Firmicutes and Cyanobacteria with plasma LPC 18:1. Thus, ultrafine particles ingestion alters gut microbiota composition, accompanied by increased atherogenic lipid metabolites. These findings implicate the gut-vascular axis in a atherosclerosis model. PMID:28211537

Anti-atherogenic effect of chromium picolinate in streptozotocin-induced experimental diabetes.

PubMed

Sundaram, Bhuvaneshwari; Singhal, Kirti; Sandhir, Rajat

2013-03-01

Several studies have implicated changes in the levels of trace elements in diabetes. Chromium is one such element that seems to potentiate insulin action, thereby regulating carbohydrate and lipid metabolism. The aim of the present study was to evaluate the effect of chromium supplementation as chromium picolinate on the lipid profile of streptozotocin (STZ)-induced diabetic rats. Rats were rendered diabetic by a single injection of STZ (50 mg/kg, i.p.). Chromium picolinate (1 mg/kg per day, p.o.) was administered to rats for a period of 4 weeks. At the end of the treatment period, plasma total lipids, triglycerides, total cholesterol and lipoprotein levels were determined, as was hepatic glucose-6-phosphate dehydrogenase activity. Total plasma lipids increased significantly in diabetic rats and this increase was ameliorated by chromium treatment for 4 weeks. Elevated total lipids in diabetic rats were due to increased plasma triglyceride and cholesterol levels. Chromium supplementation lowered plasma triglyceride and cholesterol levels to near normal. Chromium treatment also normalized low-density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein-cholesterol levels and improved the total cholesterol:high-density lipoprotein-cholesterol (HDL-C) and HDL-C:LDL-C ratios, suggesting an anti-atherogenic effect. In addition to improving the plasma lipid profile, chromium supplementation normalized liver glucose-6-phosphate dehydrogenase activity in diabetic rats. These results provide evidence that chromium picolinate effectively attenuates the dyslipidemia associated with diabetes and thus can be used as an adjuvant therapy in the treatment of diabetes and its associated complications. © 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Interactive effects of salinity and elevated CO2 levels on juvenile eastern oysters, Crassostrea virginica.

PubMed

Dickinson, Gary H; Ivanina, Anna V; Matoo, Omera B; Pörtner, Hans O; Lannig, Gisela; Bock, Christian; Beniash, Elia; Sokolova, Inna M

2012-01-01

Rising levels of atmospheric CO(2) lead to acidification of the ocean and alter seawater carbonate chemistry, which can negatively impact calcifying organisms, including mollusks. In estuaries, exposure to elevated CO(2) levels often co-occurs with other stressors, such as reduced salinity, which enhances the acidification trend, affects ion and acid-base regulation of estuarine calcifiers and modifies their response to ocean acidification. We studied the interactive effects of salinity and partial pressure of CO(2) (P(CO2)) on biomineralization and energy homeostasis in juveniles of the eastern oyster, Crassostrea virginica, a common estuarine bivalve. Juveniles were exposed for 11 weeks to one of two environmentally relevant salinities (30 or 15 PSU) either at current atmospheric P(CO2) (∼400 μatm, normocapnia) or P(CO2) projected by moderate IPCC scenarios for the year 2100 (∼700-800 μatm, hypercapnia). Exposure of the juvenile oysters to elevated P(CO2) and/or low salinity led to a significant increase in mortality, reduction of tissue energy stores (glycogen and lipid) and negative soft tissue growth, indicating energy deficiency. Interestingly, tissue ATP levels were not affected by exposure to changing salinity and P(CO2), suggesting that juvenile oysters maintain their cellular energy status at the expense of lipid and glycogen stores. At the same time, no compensatory upregulation of carbonic anhydrase activity was found under the conditions of low salinity and high P(CO2). Metabolic profiling using magnetic resonance spectroscopy revealed altered metabolite status following low salinity exposure; specifically, acetate levels were lower in hypercapnic than in normocapnic individuals at low salinity. Combined exposure to hypercapnia and low salinity negatively affected mechanical properties of shells of the juveniles, resulting in reduced hardness and fracture resistance. Thus, our data suggest that the combined effects of elevated P(CO2) and fluctuating salinity may jeopardize the survival of eastern oysters because of weakening of their shells and increased energy consumption.

Mixed dyslipidemias in primary care patients in France.

PubMed

Laforest, Laurent; Ambegaonkar, Baishali M; Souchet, Thierry; Sazonov, Vasilisa; Van Ganse, Eric

2012-01-01

To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients.

ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice.

PubMed

Xiao, Hong-Bo; Wang, Ji-Ying; Sun, Zhi-Liang

2017-12-01

Previous investigations have shown that inflammation induces changes in lipid and lipoprotein metabolism, and increased expression of angiopoietin-like protein 3 (ANGPTL3) contributes to the development of dyslipidemia. Here we investigated whether there is a correlation between increased ANGPTL3 expression and dyslipidemia in mastitis mice. Thirty mice were divided into two groups: control group and Staphylococcus aureus (S. aureus)-induced mastitis mice group. Changes in the levels of blood lipids [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)]; activity of myeloperoxidase (MPO); concentrations of plasma inflammation biomarkers [interferon-γ (IFNγ), tumor necrosis factor α (TNFα), and interleukin-1α (IL-1α)]; concentration of plasma ANGPTL3 protein; lipoprotein lipase (LPL) activities in postheparin plasma; expressions of hepatic N-acetylgalactosaminyltransferase 2 (GALNT2), hepatic ANGPTL3 and adipose LPL were determined. The major results indicated specific pathological mammary tissue changes, elevated MPO activity, reduced GALNT2 mRNA expression, elevated ANGPTL3 mRNA and protein expression and reduced LPL mRNA and protein expression. In plasma samples the S.aureus infused mice displayed elevated ANGPTL3 protein concentration, TG, TC and LDL-C levels, and reduced postheparin LPL activities and HDL-C level. The data suggests that ANGPTL3 is part of the machinery causing dyslipidemia majorily via LPL inhibition in mastitis mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Fuel use and metabolic response to endurance exercise: a wind tunnel study of a long-distance migrant shorebird.

PubMed

Jenni-Eiermann, Susanne; Jenni, Lukas; Kvist, Anders; Lindström, Ake; Piersma, Theunis; Visser, G Henk

2002-08-01

This study examines fuel use and metabolism in a group of long-distance migrating birds, red knots Calidris canutus (Scolopacidae), flying under controlled conditions in a wind tunnel for up to 10 h. Data are compared with values for resting birds fasting for the same time. Plasma levels of free fatty acids, glycerol and uric acid were elevated during flight, irrespective of flight duration (1-10 h). Triglyceride levels, the estimated concentration of very-low-density lipoproteins (VLDLs) and beta-hydroxybutyrate levels were lower during flight, while glucose levels did not change. In flying birds, plasma levels of uric acid and lipid catabolites were positively correlated with the residual variation in body mass loss, and lipid catabolites with energy expenditure (as measured using the doubly labelled water method), after removing the effect of initial body mass. The plasma metabolite levels indicate: (i) that the rates of catabolism of lipids from adipose tissue and of protein are higher during flight; (ii) that low ketone body concentrations probably facilitate fatty acid release from adipose tissue; (iii) that low triglyceride and VLDL levels do not indicate the use of an additional pathway of fatty acid delivery, as found in small birds; and (iv) that the relationships between energy expenditure, body mass loss and metabolic pattern suggest that a higher individual energy expenditure entails a higher rate of catabolism of both lipids and protein and not a shift in fuel substrate.

Colostrum supplementation protects against exercise - induced oxidative stress in skeletal muscle in mice

PubMed Central

2012-01-01

Background This study examined the effects of bovine colostrum on exercise –induced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum) and each group had three subgroups (day 0, 21 and 42). Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle. Results Exercise—induced a significant oxidative stress in skeletal muscles as evidenced by the elevated lipid hydroperoxides and xanthine oxidase levels. There was a significant decrease in skeletal muscle total antioxidants and superoxide dismutase levels. Daily colostrum supplement significantly reduced the lipid hydroperoxides and xanthine oxidase enzyme level and increased the total antioxidant levels in the leg muscle. Conclusion Thus, the findings of this study showed that daily bovine colostrum supplementation was beneficial to skeletal muscle to reduce the oxidant-induced damage during muscular exercise. PMID:23173926

Metabolic engineering of sugarcane to accumulate energy-dense triacylglycerols in vegetative biomass

DOE PAGES

Zale, Janice; Jung, Je Hyeong; Kim, Jae Yoon; ...

2015-06-08

Elevating the lipid content in vegetative tissues has emerged as a new strategy for increasing energy density and biofuel yield of crops. Storage lipids in contrast to structural and signaling lipids are mainly composed of glycerol esters of fatty acids, also known as triacylglycerol (TAG). TAGs are one of the most energy-rich and abundant forms of reduced carbon available in nature. Therefore, altering the carbon-partitioning balance in favour of TAG in vegetative tissues of sugarcane, one of the highest yielding biomass crops, is expected to drastically increase energy yields. We report metabolic engineering to elevate TAG accumulation in vegetative tissuesmore » of sugarcane. Constitutive co-expression of WRINKLED1 (WRI1), diacylglycerol acyltransferase1-2 (DGAT1-2) and oleosin1 (OLE1) and simultaneous cosuppression of ADP-glucose pyrophosphorylase (AGPase) and a subunit of the peroxisomal ABC transporter1 (PXA1) in transgenic sugarcane elevated TAG accumulation in leaves or stems by 95- or 43-fold to 1.9% or 0.9% of dry weight (DW), respectively, while expression or suppression of one to three of the target genes increased TAG levels by 1.5- to 9.5-fold. Accumulation of TAG in vegetative progeny plants was consistent with the results from primary transgenics and contributed to a total fatty acid content of up to 4.7% or 1.7% of DW in mature leaves or stems, respectively. We saw lipid droplets in mesophyll cells of transgenic leaves by confocal fluorescence microscopy. These results provide the basis for optimizations of TAG accumulation in sugarcane and other high yielding biomass grasses and will open new prospects for biofuel applications.« less

Natural honey lowers plasma glucose, C-reactive protein, homocysteine, and blood lipids in healthy, diabetic, and hyperlipidemic subjects: comparison with dextrose and sucrose.

PubMed

Al-Waili, Noori S

2004-01-01

This study included the following experiments: (1) effects of dextrose solution (250 mL of water containing 75 g of dextrose) or honey solution (250 mL of water containing 75 g of natural honey) on plasma glucose level (PGL), plasma insulin, and plasma C-peptide (eight subjects); (2) effects of dextrose, honey, or artificial honey (250 mL of water containing 35 g of dextrose and 40 g of fructose) on cholesterol and triglycerides (TG) (nine subjects); (3) effects of honey solution, administered for 15 days, on PGL, blood lipids, C-reactive protein (CRP), and homocysteine (eight subjects); (4) effects of honey or artificial honey on cholesterol and TG in six patients with hypercholesterolemia and five patients with hypertriglyceridemia; (5) effects of honey for 15 days on blood lipid and CRP in five patients with elevated cholesterol and CRP; (6) effects of 70 g of dextrose or 90 g of honey on PGL in seven patients with type 2 diabetes mellitus; and (7) effects of 30 g of sucrose or 30 g of honey on PGL, plasma insulin, and plasma C-peptide in five diabetic patients. In healthy subjects, dextrose elevated PGL at 1 (53%) and 2 (3%) hours, and decreased PGL after 3 hours (20%). Honey elevated PGL after 1 hour (14%) and decreased it after 3 hours (10%). Elevation of insulin and C-peptide was significantly higher after dextrose than after honey. Dextrose slightly reduced cholesterol and low-density lipoprotein-cholesterol (LDL-C) after 1 hour and significantly after 2 hours, and increased TG after 1, 2, and 3 hours. Artificial honey slightly decreased cholesterol and LDL-C and elevated TG. Honey reduced cholesterol, LDL-C, and TG and slightly elevated high-density lipoprotein-cholesterol (HDL-C). Honey consumed for 15 days decreased cholesterol (7%), LDL-C (1%), TG (2%), CRP (7%), homocysteine (6%), and PGL (6%), and increased HDL-C (2%). In patients with hypertriglyceridemia, artificial honey increased TG, while honey decreased TG. In patients with hyperlipidemia, artificial honey increased LDL-C, while honey decreased LDL-C. Honey decreased cholesterol (8%), LDL-C (11%), and CRP (75%) after 15 days. In diabetic patients, honey compared with dextrose caused a significantly lower rise of PGL. Elevation of PGL was greater after honey than after sucrose at 30 minutes, and was lower after honey than it was after sucrose at 60, 120, and 180 minutes. Honey caused greater elevation of insulin than sucrose did after 30, 120, and 180 minutes. Honey reduces blood lipids, homocysteine, and CRP in normal and hyperlipidemic subjects. Honey compared with dextrose and sucrose caused lower elevation of PGL in diabetics.

Ameliorative effect of hydro-methanolic extract from roots of Rauwolfia serpentina on some biochemical parameters of type 1 diabetic mice.

PubMed

Azmi, Muhammad Bilal; Qureshi, Shamim A; Ahmed, Syed Danish Haseen; Mudassir, Hina Akram; Imtiaz, Fauzia; Rais, Sumera; Khan, Auwais Ahmed; Ahsan, Muhammad

2018-03-01

Present work seeks to investigate the biochemical parameters in terms of hypoglycemic and hypolipidemic effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 (alloxan induced) diabetic mice. Animals were divided into seven groups, four control groups, and three were test groups (HyMREt at 50, 100, & 150mg/kg). Each treatment was repeated for 14 days regularly in all seven respective groups and afterwards the body weights, fasting blood glucose (FBG), insulin, and serum lipid levels were determined. Total body weights of diabetic mice treated with HyMREt extract were dose dependently (p<0.05) improved. FBG of test groups were significantly (p<0.0001) reduced in comparison with diabetic controls which displayed elevated fasting blood glucose level. The insulin levels of HyMREt treated groups were significantly (p<0.0001) higher than those of diabetic controls. Lower triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and very low density lipoprotein cholesterol (VLDL-c) whereas elevated level of high density lipoprotein cholesterol (HDL-c) were observed in test dose treated groups. In comparison with diabetic controls, the converse levels of serum lipid were observed. Significant improvement in cardio-protective indices and coronary risk index was also observed. Findings of present study support the hypoglycemic and hypolipidemic potential of HyMREt of R. serpentina.

Advances in lipid-lowering therapy through gene-silencing technologies.

PubMed

Nordestgaard, Børge G; Nicholls, Stephen J; Langsted, Anne; Ray, Kausik K; Tybjærg-Hansen, Anne

2018-05-01

New treatment opportunities are emerging in the field of lipid-lowering therapy through gene-silencing approaches. Both antisense oligonucleotide inhibition and small interfering RNA technology aim to degrade gene mRNA transcripts to reduce protein production and plasma lipoprotein levels. Elevated levels of LDL, remnant lipoproteins, and lipoprotein(a) all cause cardiovascular disease, whereas elevated levels of triglyceride-rich lipoproteins in some patients can cause acute pancreatitis. The levels of each of these lipoproteins can be reduced using gene-silencing therapies by targeting proteins that have an important role in lipoprotein production or removal (for example, the protein products of ANGPTL3, APOB, APOC3, LPA, and PCSK9). Using this technology, plasma levels of these lipoproteins can be reduced by 50-90% with 2-12 injections per year; such dramatic reductions are likely to reduce the incidence of cardiovascular disease or acute pancreatitis in at-risk patients. The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet counts. However, newer-generation drugs are more efficiently delivered to liver cells, requiring lower drug doses, which leads to fewer adverse effects. Although these findings are promising, robust evidence of cardiovascular disease reduction and long-term safety is needed before these gene-silencing technologies can have widespread implementation. Before the availability of such evidence, these drugs might have roles in patients with unmet medical needs through orphan indications.

Enhanced lipid accumulation and biodiesel production by oleaginous Chlorella protothecoides under a structured heterotrophic-iron (II) induction strategy.

PubMed

Li, Yuqin; Mu, Jinxiu; Chen, Di; Xu, Hua; Han, Fangxin

2015-05-01

A structured heterotrophic-iron (II) induction (HII) strategy was proposed to enhance lipid accumulation in oleaginous Chlorella protothecoides. C. protothecoides subjected to heterotrophic-iron (II) induction achieved a favorable lipid accumulation up to 62 % and a maximum lipid productivity of 820.17 mg/day, representing 2.78-fold and 3.64-fold increase respectively over heterotrophic cultivation alone. HII-induced cells produced significantly elevated levels of 16:0, 18:1(Δ9), and 18:2(Δ9,12) fatty acids (over 90 %). The lipid contents and plant lipid-like fatty acid compositions exhibit the potential of HII-induced C. protothecoides as biodiesel feedstock. Furthermore, 31 altered proteins in HII-induced algal cells were successfully identified. These differentially expressed proteins were assigned into nine molecular function categories, including carbohydrate metabolism, lipid biosynthesis, Calvin cycle, cellular respiration, photosynthesis, energy and transport, protein biosynthesis, regulate and defense, and unclassified. Analysis using the Kyoto encyclopedia of genes and genomes and gene ontology annotation showed that malic enzyme, acyltransferase, and ACP were key metabolic checkpoints found to modulate lipid accumulation in C. protothecoides. The results provided possible applications of HII cultivation strategy in other microalgal species and new possibilities in developing genetic and metabolic engineering microalgae for desirable lipid productivity.

Dyslipidemia in women with polycystic ovary syndrome.

PubMed

Kim, Jin Ju; Choi, Young Min

2013-05-01

Dyslipidemia is a very common metabolic abnormality in women with polycystic ovary syndrome (PCOS). Insulin resistance is a key pathophysiology of PCOS, thus dyslipidemia in women with PCOS may be consistent with those found in an insulin resistant state. In recent meta-analysis, triglycerides and low-density lipoprotein (LDL) cholesterol levels were 26 mg/dL and 12 mg/dL higher, and high-density lipoprotein cholesterol concentration was 6 mg/dL lower in women with PCOS than those of controls. Alterations in LDL quality also have been reported in women with PCOS: women with PCOS have an increased proportion of atherogenic small dense LDL or decreased mean LDL particle size. However, in a recent Korean study, non-obese Korean women with PCOS had no significant quantitative or qualitative changes in LDL cholesterol profile. Lipoprotein (a) has been identified as an independent risk factor for coronary heart disease, and its elevation in PCOS patients has been consistently reported in diverse studies including non-obese Korean population. Some studies have investigated apolipoprotein (Apo) A-I and ApoC-I levels in women with PCOS and levels of ApoA-I, which has cardio-protective effects, were significantly lower in women with PCOS than those of controls. ApoC-I is known to increase the postprandial serum lipid level that is common in coronary artery disease patients, and one study reported that such an elevation may be the earliest variation of lipid abnormality in women with PCOS. In conclusion, women with PCOS should receive a complete lipid test, and lifestyle modification, including diet and exercise, is the first line therapy for all women with PCOS and is particularly important for those with dyslipidemia.

[Changes of serum aminotransferase in children with obstructive sleep apnea hypopnea syndrome].

PubMed

Chen, Zhenjiang; Duo, Likun

2013-08-01

Obstructive sleep apnea hypopnea syndrome (OSAHS) and non-alcoholic fatty liver disease (NAFLD) are both strongly associated with obesity. Whether OSAHS is an independent risk factor for liver injury or not is uncertain. To assess the hypothesis that OSAHS is associated with liver injury independent of obesity. One hundred and thirty children with OSAHS and 77 children with primary snoring(PS) were enrolled. Polysomnography was performed. Body mass index (BMI), liver function tests, serum lipids, fasting plasma glucose (FPG), and insulin (INS) were measured. Seventeen children of OSAHS had elevated serum aminotransferase levels,while only 2 children of non-OSAHS had elevated serum aminotransferase in healthy control group (chi2 = 5.18, P < 0.05; OR = 5.64 CI 1.27-24.97). Fifteen children of obese had elevated serum aminotransferase levels, while only 4 children had elevated serum aminotransferase in non-obese group (chi2 = 4.58, P < 0.05; (OR = 1.97 CI 1.06-3.67). Seventy cases of obese children, 15 cases of elevated aminotransferase levels (21.4%), namely fatty liver patients, of these children, 14 had OSAHS (93.3%). In contrast, OSAHS was present in only 67.3% of obese children without elevated aminotransferase. OSAHS may be a risk factor for liver injury independent of obesity; Increased liver enzyme levels are frequently found in obese snoring children, particularly among those with OSAHS.

Combined dyslipidemia in childhood.

PubMed

Kavey, Rae-Ellen W

2015-01-01

Combined dyslipidemia (CD) is now the predominant dyslipidemic pattern in childhood, characterized by moderate-to-severe elevation in triglycerides and non-high-density lipoprotein cholesterol (non-HDL-C), minimal elevation in low-density lipoprotein cholesterol (LDL-C), and reduced HDL-C. Nuclear magnetic resonance spectroscopy shows that the CD pattern is represented at the lipid subpopulation level as an increase in small, dense LDL and in overall LDL particle number plus a reduction in total HDL-C and large HDL particles, a highly atherogenic pattern. In youth, CD occurs almost exclusively with obesity and is highly prevalent, seen in more than 40% of obese adolescents. CD in childhood predicts pathologic evidence of atherosclerosis and vascular dysfunction in adolescence and young adulthood, and early clinical cardiovascular events in adult life. There is a tight connection between CD, visceral adiposity, insulin resistance, nonalcoholic fatty liver disease, and the metabolic syndrome, suggesting an integrated pathophysiological response to excessive weight gain. Weight loss, changes in dietary composition, and increases in physical activity have all been shown to improve CD significantly in children and adolescents in short-term studies. Most importantly, even small amounts of weight loss are associated with significant decreases in triglyceride levels and increases in HDL-C levels with improvement in lipid subpopulations. Diet change focused on limitation of simple carbohydrate intake with specific elimination of all sugar-sweetened beverages is very effective. Evidence-based recommendations for initiating diet and activity change are provided. Rarely, drug therapy is needed, and the evidence for drug treatment of CD in childhood is reviewed. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Dyslipidemia in PCOS.

PubMed

Wild, Robert A

2012-03-10

Life-long apolipoprotein lipid metabolic dysfunction in women with PCOS exaggerates the risk for cardiovascular disease (CVD) with aging. The dysfunction has involved insulin resistance (IR), which occurs in most women with PCOS. Women with PCOS have androgen excess, IR, variable amounts of estrogen exposure, and many environmental factors, all of which can influence lipid metabolism. On average, women with PCOS were higher triglyceride [26.39 95% CI (17.24, 35.54)], lower HDL-cholesterol [6.41 95% CI (3.69, 9.14)], and higher non HDL cholesterol levels [18.82 95% CI (15.53, 22.11)] than their non-PCOS counterparts. They have higher ApoCIII/ApoCII ratios and higher ApoCI even if they are not obese. ApoC1 elevation in women with PCOS needs to be further evaluated as a marker of dysfunction and potential CVD risk. ApoB measurements track with non-HDL cholesterol as a surrogate for increased atherogenic circulating small LDL particles. Elevated triglycerides and waist circumference predict CVD risk and women with PCOS often have these phenotypes. Diet and exercise interventions followed by selective lipid lowering medications are encouraged to normalize the dyslipidemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Combination of Vildagliptin and Pioglitazone in Experimental Type 2 Diabetes in Male Rats.

PubMed

Refaat, Rowaida; Sakr, Ahmed; Salama, Mona; El Sarha, Ashgan

2016-09-01

Preclinical Research The majority of studies on vildagliptin and pioglitazone have focused on their combination in glycemic control. The aim of the present study was to investigate their effects in combination on (i) hyperglycemia-induced oxidative stress and inflammation and (ii) on organs involved in the pathophysiology of diabetes, pancreas, kidney and liver. Type 2 diabetes was induced using low-dose streptozotocin in male Wistar rats. Diabetic rats were treated for 4 weeks, with vildagliptin (10 mg/kg/day), pioglitazone (10 mg/kg/day) and their combination. Diabetic rats showed elevated fasting serum glucose, fasting serum insulin, serum transaminases together with a deleterious lipid profile and elevated serum creatinine and urea concentrations. Serum levels of the inflammatory markers tumor necrosis factor-α (TNF-α) and nitrite/nitrate were also elevated compared to normal rats. Oxidative stress was manifested by lowered hepatic reduced glutathione (GSH) and increased malondialdehyde (MDA) levels. Pancreatic sections from diabetic rats showed degenerated islets with poorly maintained architecture that was prevented by drug treatment. Pioglitazone was generally more effective than vildagliptin in the studied parameters except for the lipid profile where the effect of both drugs was comparable and for the liver enzymes and renal parameters where vildagliptin was more effective. The combination of vildagliptin and pioglitazone produced superior effects than either drug alone. Drug Dev Res 77 : 251-257, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat.

PubMed

Han, Ying; Lin, Min; Wang, Xiaobin; Guo, Keke; Wang, Shanshan; Sun, Mengfei; Wang, Jiao; Han, Xiaoyu; Fu, Ting; Hu, Yang; Fu, Jihua

2015-03-01

Our previous study has demonstrated that long-term stress, known as chronic stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic pathways were impacted by CS in the HFD-fed rat. Male Sprague-Dawley rats (6 weeks of age, n = 8 per group) were fed with either standard diet or HFD with or without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and lipid profile markers in serum and liver, and enzymes involved in de novo lipogenesis (DNL) of fatty acids (FAs) and cholesterol, β-oxidation, FAs uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly in the liver were detected. CS exposure reduced hepatic lipidosis but further elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats. There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR and western blot assays showed that CS exposure significantly promoted hepatic VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact on DNL, β-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed rats. This phenomenon was in accordance with elevated serum glucocorticoid level. The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed rats is VLDL assembly which might be regulated by glucocorticoid.

Heat stress dictates microbial lipid composition in hydrothermal marine sediments

NASA Astrophysics Data System (ADS)

Sollich, M.; Yoshinaga, M. Y.; Häusler, S.; Hinrichs, K. U.; Bühring, S. I.

2016-02-01

Abundant and diverse microbial communities inhabit hydrothermal marine sediments. Since ion permeability of membranes increases with temperature archaea and bacteria that use proton/sodium as coupling ions for bioenergetics must constantly adjust their cytoplasmic membrane permeability, which in turn is mostly controlled by the lipid composition. Here, we investigated a thermal gradient across a marine sediment field (ranging from 18 to over 100°C) and tested the concept that membrane lipids provide a major biochemical basis for cellular bioenergetics of archaea and bacteria under stressful conditions. Reflecting the lower ion permeability of the ether-linked isoprenoidal lipids, we found that archaea dominate over bacteria in sediments of >50 °C. Moreover, a detailed examination of the molecular lipid species revealed a quandary: low membrane permeability concomitantly with increased fluidity is required for energy conservation of both archaea and bacteria under heat stress. For instance, bacterial fatty acids were found to increase chain length in concert with a higher degree of unsaturation at elevated sediment temperatures while archaeal tetraethers were observed to show a higher degree of bulking (e.g. methylation and H-shaped) and fluidity (i.e. cyclization) under elevated temperatures. In addition, our data indicate that strong intermolecular hydrogen bonding at the headgroup level of archaeal glycolipids and bacterial sphingolipids may provide ideal membrane stability to attain the required balance between low permeability and a more fluidized configuration. For example, sphingolipids may stabilize bacterial phospholipids into lipid domains, enabling bacteria to thrive in heated sediments under unfavorable thermodynamic conditions. The scientific marriage of lipidomics and bioenergetics described here provides a new dimension for understanding microbial life in natural environments.

Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea.

PubMed

Kheirandish-Gozal, Leila; Sans Capdevila, Oscar; Kheirandish, Ebrahim; Gozal, David

2008-01-01

Fatty liver disease (FLD) is a highly prevalent condition in obese (Ob) children, who are at increased risk for obstructive sleep apnea (OSA). However, the contribution of OSA to FLD remains unknown. Prospective study. Polysomnographic evaluation and assessment of plasma levels of insulin, glucose, and lipids, and liver function tests. A total of 518 consecutive snoring children 4 to 17 years of age who were being evaluated for habitual snoring and suspected OSA. A total of 376 children had body mass index z score of < 1.20 (non-Ob children), 3 children (<1%) had elevated serum aminotransferase (LFT) levels, and 248 had OSA (65.9%). Among the 142 overweight/Ob children, 46 had elevated LFT levels (32.4%); of these children, 42 had OSA (91.3%). In contrast, OSA was present in only 71.8% of Ob children without elevated LFT level (p < 0.01). Insulin resistance and hyperlipidemia were more likely to occur in children with FLD. Furthermore, FLD was improved after treatment of OSA in 32 of 42 Ob children (p < 0.0001). Increased liver enzyme levels are frequently found in Ob snoring children, particularly among those with OSA and/or metabolic dysfunction. Effective treatment of OSA results in improved liver function test results in the vast majority of these patients.

Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity

PubMed Central

Pereira, Sandra; Yu, Wen Qin; Frigolet, María E; Beaudry, Jacqueline L; Shpilberg, Yaniv; Park, Edward; Dirlea, Cristina; Nyomba, B L Grégoire; Riddell, Michael C; Fantus, I George; Giacca, Adria

2013-01-01

We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase. PMID:23328071

Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After Surgery for Renal Cell Carcinoma.

PubMed

Haddad, Ahmed Q; Jiang, Lai; Cadeddu, Jeffrey A; Lotan, Yair; Gahan, Jeffrey C; Hynan, Linda S; Gupta, Neil; Raj, Ganesh V; Sagalowsky, Arthur I; Margulis, Vitaly

2015-12-01

To evaluate the association of statin use and preoperative serum lipid parameters with oncologic outcomes following surgery for renal cell carcinoma. A total of 850 patients who underwent surgery for localized renal cell carcinoma at our institution from 2000 to 2012 were included. Use of statins, preoperative serum lipid profile, and comprehensive clinicopathologic features were retrospectively recorded. Kaplan-Meier analysis and multivariate Cox proportional hazards model were employed to compare survival outcomes. There were 342 statin users and 508 non-users. Median follow-up was 25.0 months. Statin users were older, had greater body mass index, and had worse performance status than non-users. Tumor pathologic characteristics were balanced between groups. Five-year recurrence free survival (RFS) was 77.9% for non-users compared with 87.6% for statin users (P = .004). After adjustment for clinicopathologic variables, statin use was independently associated with improved RFS (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.33-0.86, P = .011) and overall survival (HR 0.45, 95%CI 0.28-0.71, P = .001). In patients with available serum lipid parameters (n = 193), 5-year RFS was 83.8% for patients with triglycerides <250 mg/dL compared with 33.3% for those with triglycerides >250 mg/dL (P <.0001). Elevated serum triglycerides (>250 mg/dL) was independently associated with worse RFS (HR 2.69, 95%CI 1.22-5.93, P = .015) on multivariate analysis. Statin use was independently associated with improved survival, whereas elevated serum triglyceride levels correlated with worse oncologic outcomes in this cohort. These findings warrant validation in prospective studies. Copyright © 2015 Elsevier Inc. All rights reserved.

Veratric acid ameliorates hyperlipidemia and oxidative stress in Wistar rats fed an atherogenic diet.

PubMed

Raja, Boobalan; Saravanakumar, Murugesan; Sathya, Gopal

2012-07-01

An investigation was made to reveal the protective effects of veratric acid (VA), a phenolic acid against atherogenic diet-induced hyperlipidemic rats. Male albino Wistar rats were fed with atherogenic diet (4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil) daily for 30 days and treated with VA (40 mg/kg body weight) daily for a period of 30 days. Rats fed with atherogenic diet showed significant (P < 0.05) elevation in the level of plasma lipids, systolic and diastolic blood pressure, oxidative stress markers (thiobarbituric acid reactive substances, lipid peroxides) and significant (P < 0.05) reduction in the activities of enzymatic (superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (vitamin C, vitamin E, and reduced glutathione) antioxidants in erythrocytes, plasma, and tissues (liver, kidney, and aorta). Oral administration of VA (40 mg/kg body weight) for 30 days to atherogenic diet fed rats markedly attenuates systolic, diastolic blood pressure and lipid peroxidation products. Further, VA treatment significantly improved enzymatic and non-enzymatic antioxidants levels and showed beneficial effects on lipid profile in atherogenic diet rats. All the above alterations were supported by histopathological observations. These results indicate that oral administration of VA ameliorates atherogenic diet-induced hyperlipidemia in rats by its free radical scavenging; improving the antioxidants and lipid lowering properties.

Exhaled ethane: an in vivo biomarker of lipid peroxidation in interstitial lung diseases.

PubMed

Kanoh, Soichiro; Kobayashi, Hideo; Motoyoshi, Kazuo

2005-10-01

Oxidative stress plays a role in the pathogenesis and progression of interstitial lung disease (ILD). Exhaled ethane is a product of lipid peroxidation that has been proposed as a biomarker of oxidative stress in vivo. To determine whether the exhaled ethane level is elevated in patients with ILD and to compare it with other clinical parameters. Breath samples were collected from 34 patients with ILD, including 13 with idiopathic pulmonary fibrosis (IPF), 9 patients with cryptogenic organizing pneumonia, 6 patients with collagen vascular disease-associated interstitial pneumonia, and 6 patients with pulmonary sarcoidosis. Gas samples were obtained at hospital admission and after 3 weeks. After each expired sample was concentrated using a trap-and-purge procedure, the ethane level was analyzed by gas chromatography. Exhaled ethane levels were elevated in ILD patients (n = 34, mean +/- SD, 8.5 +/- 8.0 pmol/dL) compared with healthy volunteers (n = 16, 2.9 +/- 1.0 pmol/dL; p < 0.001). Serial measurements revealed that increase and decrease of ethane levels were largely consistent with the clinical course. Four patients with IPF who had persistently high ethane levels died or deteriorated, whereas those with ethane levels < 5.0 pmol/dL remained stable or improved. Exhaled ethane concentrations were positively correlated with levels of lactate dehydrogenase (Spearman rank correlation coefficient [rs], 0.28, p = 0.026) and C-reactive protein (rs, 0.38, p = 0.025) and were inversely correlated with Pa(O2) (rs, - 0.40, p = 0.0026). Patients showing increased uptake on (67)Ga scintigraphy demonstrated higher ethane levels (n = 19, 7.5 +/- 5.7 pmol/dL) compared with those who did not show increased uptake on scintigraphy (n = 10, 3.0 +/- 2.4 pmol/dL; p < 0.01). Exhaled ethane is elevated in patients with ILD and is correlated with the clinical outcome, suggesting that it provides useful information about ongoing oxidative stress, and thereby disease activity and severity in ILD.

Elevated prostacyclin biosynthesis in mice impacts memory and anxiety-like behavior.

PubMed

Vollert, Craig; Ohia, Odochi; Akasaka, Hironari; Berridge, Casey; Ruan, Ke-He; Eriksen, Jason L

2014-01-01

Prostacyclin is an endogenous lipid metabolite with properties of vasodilation and anti-platelet aggregation. While the effects of prostacyclin on the vascular protection have been well-documented, the role of this eicosanoid in the central nervous system has not been extensively studied. Recently, a transgenic mouse containing a hybrid enzyme, of cyclooxygenase-1 linked to prostacyclin synthase, was developed that produces elevated levels of prostacyclin in vivo. The goal of this study was to investigate whether increased prostacyclin biosynthesis could affect behavioral phenotypes in mice. Our results uncovered that elevated levels of prostacyclin broadly affect both cognitive and non-cognitive behaviors, including decreased anxiety-like behavior and improved learning in the fear-conditioning memory test. This study demonstrates that prostacyclin plays an important, but previously unrecognized, role in central nervous system function and behavior. Copyright © 2013 Elsevier B.V. All rights reserved.

Differential effect of corn oil-based low trans structured fat on the plasma and hepatic lipid profile in an atherogenic mouse model: comparison to hydrogenated trans fat

PubMed Central

2011-01-01

Background Trans fat are not desirable in many aspects on health maintenance. Low trans structured fats have been reported to be relatively more safe than trans fats. Methods We examined the effects of low trans structured fat from corn oil (LC), compared with high trans fat shortening, on cholesterol and fatty acid metabolism in apo E deficient mice which is an atherogenic animal model. The animals were fed a high trans fat (10% fat: commercial shortening (CS)) or a low trans fat (LC) diet for 12 weeks. Results LC decreased apo B and hepatic cholesterol and triglyceride concentration compared to the CS group but significantly increased plasma total cholesterol and triglyceride concentration and fecal lipids with a simultaneous increase in HDL-cholesterol level, apo A-I, and the ratio of HDL-cholesterol to total cholesterol (HTR). Reduction of hepatic lipid levels by inclusion of LC intake was observed alongside modulation of hepatic enzyme activities related to cholesterol esterification, fatty acid metabolism and fecal lipids level compared to the CS group. The differential effects of LC intake on the plasma and hepatic lipid profile seemed to be partly due to the fatty acid composition of LC which contains higher MUFA, PUFA and SFA content as well as lower content of trans fatty acids compared to CS. Conclusions We suggest that LC may exert a dual effect on plasma and hepatic lipid metabolism in an atherogenic animal model. Accordingly, LC, supplemented at 10% in diet, had an anti-atherogenic effect on these apo E-/- mice, and increased fecal lipids, decreased hepatic steatosis, but elevated plasma lipids. Further studies are needed to verify the exact mode of action regarding the complex physiological changes and alteration in lipid metabolism caused by LC. PMID:21247503

Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.

PubMed

El-Sherbeeny, Nagla A; Nader, Manar A; Attia, Ghalia M; Ateyya, Hayam

2016-12-01

Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.

Anti-obesity and anti-diabetic effects of ethanol extract of Artemisia princeps in C57BL/6 mice fed a high-fat diet.

PubMed

Yamamoto, Norio; Kanemoto, Yuki; Ueda, Manabu; Kawasaki, Kengo; Fukuda, Itsuko; Ashida, Hitoshi

2011-01-01

Artemisia princeps is commonly used as a food ingredient and in traditional Asian medicine. In this study, we examined the effects of long-term administration of an ethanol extract of A. princeps (APE) on body weight, white adipose tissue, blood glucose, insulin, plasma and hepatic lipids, and adipocytokines in C57BL/6 mice fed a high-fat diet. Daily feeding of a 1% APE diet for 14 weeks normalized elevated body weight, white adipose tissue, and plasma glucose and insulin levels, and delayed impaired glucose tolerance in mice a fed high-fat diet. These events were not observed in mice fed a control diet containing 1% APE. Liver triglyceride and cholesterol levels were similar in mice fed a 1% APE-diet and those fed a control diet. In the high-fat diet groups, APE inhibited hepatic fatty acid synthase (FAS) and suppressed the elevation of plasma leptin, but had no effect on adiponectin levels. These findings suggest that the regulation of leptin secretion by APE may inhibit FAS activity with subsequent suppression of triglyceride accumulation in the liver and adipose tissues. Inhibition of lipid accumulation can, in turn, lead to improvements in impaired glucose tolerance.

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C.

PubMed

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-02-14

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 μg/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C

PubMed Central

Li, Sha; Zhao, Xi; Zhang, Yan; Zhu, Cheng-Gang; Guo, Yuan-Lin; Wu, Na-Qiong; Xu, Rui-Xia; Qing, Ping; Gao, Ying; Sun, Jing; Liu, Geng; Dong, Qian; Li, Jian-Jun

2017-01-01

Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit. PMID:27713142

Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study.

PubMed

Vrijkotte, Tanja G M; Krukziener, Náthalie; Hutten, Barbara A; Vollebregt, Karlijn C; van Eijsden, Manon; Twickler, Marcel B

2012-11-01

Elevated lipid levels during late pregnancy are associated with complications and adverse outcome for both mother and newborn. However, it is inconclusive whether a disturbed lipid profile during early pregnancy has similar negative associations. Our objective was to investigate whether nonfasting maternal total cholesterol and triglyceride levels during early pregnancy are associated with six major adverse pregnancy outcomes. Data were derived from the Amsterdam Born Children and Their Development (ABCD) cohort study. Random blood samples of nonfasting total cholesterol and triglyceride levels were determined during early gestation (median = 13, interquartile range = 12-14 wk). Outcome measures were pregnancy-induced hypertension (PIH), preeclampsia, preterm birth, small/large for gestational age (SGA/LGA), and child loss. Only nondiabetic women with singleton deliveries were included; the baseline sample consisted of 4008 women. Analysis for PIH and preeclampsia were performed in nulliparous women only (n = 2037). Mean (sd) triglyceride and total cholesterol levels were 1.33 (0.55) and 4.98 (0.87) mmol/liter, respectively. The incidence of pregnancy complications and perinatal outcomes were as follows: PIH, 4.9%; preeclampsia, 3.7%; preterm birth, 5.3%; SGA, 9.3%; LGA, 9.3%; and child loss, 1.4%. After adjustments, every unit increase in triglycerides was linearly associated with an increased risk of PIH [odds ratio (OR) = 1.60, P = 0.021], preeclampsia (OR = 1.69, P = 0.018), LGA (OR = 1.48, P < 0.001), and induced preterm delivery (OR = 1.69, P = 0.006). No associations were found for SGA or child loss. Total cholesterol was not associated with any of the outcome measures. Elevated maternal triglyceride levels measured during early pregnancy are associated with pregnancy complications and adverse pregnancy outcomes. These results suggest that future lifestyle programs in women of reproductive age with a focus on lowering triglyceride levels (i.e. diet, weight reduction, and physical activity) may help to prevent hypertensive complications during pregnancy and adverse birth outcomes.

Proton MR spectroscopy in patients with acute temporal lobe seizures.

PubMed

Castillo, M; Smith, J K; Kwock, L

2001-01-01

Decreases in N-acetyl aspartate (NAA) as seen by proton MR spectroscopy are found in hippocampal sclerosis, and elevated levels of lipids/lactate have been observed after electroconvulsive therapy. Our purpose was to determine whether increased levels of lipids/lactate are found in patients with acute seizures of hippocampal origin. Seventeen patients with known temporal lobe epilepsy underwent proton MR spectroscopy of the mesial temporal lobes within 24 hours of their last seizure. Four of them were restudied when they were seizure-free. Five healthy individuals were used as control subjects. All MR spectroscopy studies were obtained using a single-voxel technique with TEs of 135 and 270. The relationship between the presence of lipids/lactate and seizures was tested using Fisher's exact test. Mean and standard deviations for NAA/creatine (Cr) were obtained in the hippocampi in patients with seizures on initial and follow-up studies and these values were compared with those in the control subjects. Seizure lateralization was obtained in 15 patients. Of the 17 seizure locations that involved hippocampi, 16 showed lipids/lactate by proton MR spectroscopy. Of the 13 hippocampi not directly affected by seizures, 10 showed no lipids/lactate and three showed lipids/lactate. The relationship between lipids/lactate and seizure location was confirmed. A comparison of NAA/Cr ratios for the involved hippocampi with those in control subjects showed significant differences on initial MR spectroscopy; however, no significant difference was found between acute and follow-up NAA/Cr ratios in hippocampi affected by seizures. Lipids/lactate were present in the hippocampi of patients with acute seizures and decreased when the patients were seizure-free. Thus, lipids/lactate may be a sensitive marker for acute temporal lobe seizures.

L-rhamnose induces browning in 3T3-L1 white adipocytes and activates HIB1B brown adipocytes.

PubMed

Choi, Minji; Mukherjee, Sulagna; Kang, Nam Hyeon; Barkat, Jameel Lone; Parray, Hilal Ahmad; Yun, Jong Won

2018-06-01

Induction of the brown adipocyte-like phenotype in white adipocytes (browning) is considered as a novel strategy to fight obesity due to the ability of brown adipocytes to increase energy expenditure. Here, we report that L-rhamnose induced browning by elevating expression levels of beige-specific marker genes, including Cd137, Cited1, Tbx1, Prdm16, Tmem26, and Ucp1, in 3T3-L1 adipocytes. Moreover, L-rhamnose markedly elevated expression levels of proteins involved in thermogenesis both in 3T3-L1 white and HIB1B brown adipocytes. L-rhamnose treatment in 3T3-L1 adipocytes also significantly elevated protein levels of p-HSL, p-AMPK, ACOX, and CPT1 as well as reduced levels of ACC, FAS, C/EBPα, and PPARγ, suggesting its possible role in enhancement of lipolysis and lipid catabolism as well as reduced adipogenesis and lipogenesis, respectively. The quick technique of efficient molecular docking provided insight into the strong binding of L-rhamnose to the fat-digesting glycine residue of β 3 -adrenergic receptor (AR), indicating strong involvement of L-rhamnose in fat metabolism. Further examination of the molecular mechanism of L-rhamnose revealed that it induced browning of 3T3-L1 adipocytes via coordination of multiple signaling pathways through β 3 -AR, SIRT1, PKA, and p-38. To the best of our knowledge, this is the first study to demonstrate that L-rhamnose plays multiple modulatory roles in the induction of white fat browning, activation of brown adipocytes, as well as promotion of lipid metabolism, thereby demonstrating its therapeutic potential for treatment of obesity. © 2018 IUBMB Life, 70(6):563-573, 2018. © 2018 International Union of Biochemistry and Molecular Biology.

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans

PubMed Central

Hulver, Matthew W.; Berggren, Jason R.; Carper, Michael J.; Miyazaki, Makoto; Ntambi, James M.; Hoffman, Eric P.; Thyfault, John P.; Stevens, Robert; Dohm, G. Lynis; Houmard, Joseph A.; Muoio, Deborah M.

2014-01-01

Summary Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity. PMID:16213227

Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.

PubMed

Hulver, Matthew W; Berggren, Jason R; Carper, Michael J; Miyazaki, Makoto; Ntambi, James M; Hoffman, Eric P; Thyfault, John P; Stevens, Robert; Dohm, G Lynis; Houmard, Joseph A; Muoio, Deborah M

2005-10-01

Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.

[Metabolic changes associated with obesity in adults].

PubMed

Rincón, E; Ryder, E; Valbuena, H; García de Zambrano, N; Campos, G; Morales, L M; Semprún de Fereira, M; Wilhelm, I

1989-01-01

In order to find if the metabolic disorders more frequently found in our obese population were similar to the ones reported in the literature for other countries, a study was conducted in a group of 34 obese subjects (10 men and 24 women) whose only apparent alteration was a body mass index above 30 (mean value: 36.8 +/- 4.6) to obtain the relation between anthropometric measurements (Quetelet index, skinfold measures and waist/hip ratio) and plasma levels of nine biochemical parameters (including lipids, lipoproteins and glucose and insulin levels after an oral glucose load). The results revealed a tendency to the android distribution of fat in the female population, a significantly elevated triglyceride and total lipids levels and a decreased in HDL-cholesterol in both sexes. Hypercholesterolemia was present mainly in the male population. The most frequent dyslipidemia was Type IV (23%) followed by type IIb (15%). Practically none of the subjects had abnormal glycemic values after the glucose load, however the insulin levels were highly elevated in 80% of the patients, resulting in a great insulin/glucose ratios. Correlation analysis showed no association of the BMI with any biochemical parameter; only the insulin area was positively associated with anthropometric measures (mainly waist/hip ratio) and with the most altered biochemical parameter, the triglycerides. Variance analysis showed that only low HDL-cholesterol values were significantly different in patients presenting high blood pressure and familiar history of diabetes.

Mixed dyslipidemias in primary care patients in France

PubMed Central

Laforest, Laurent; Ambegaonkar, Baishali M; Souchet, Thierry; Sazonov, Vasilisa; Van Ganse, Eric

2012-01-01

Objective To determine the prevalence of single and mixed dyslipidemias among patients treated with statins in clinical practice in France. Methods This is a prospective, observational, cross-sectional, pharmacoepidemiologic study with a total of 2544 consecutive patients treated with a statin for at least 6 months. Main outcome measures Prevalence of isolated and mixed dyslipidemias of low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides among all patients and among patients at high cardiovascular risk; clinical variables associated with attainment of lipid targets/normal levels in French national guidelines. Results At least one dyslipidemia was present in 50.8% of all patients and in 71.1% of high-risk patients. Dyslipidemias of LDL-C, HDL-C, and triglycerides were present in 27.7%, 12.4%, and 28.7% of all patients, respectively, and in 51.0%, 18.2%, and 32.5% of high-risk patients, respectively. Among all subjects with any dyslipidemia, 30.9% had mixed dyslipidemias and 69.4% had low HDL-C and/or elevated triglycerides, while 30.6% had isolated elevated LDL-C; corresponding values for high-risk patients were 36.8%, 58.9%, and 41.1%. Age, gender, body mass index and Framingham Risk Score >20% were the factors significantly associated with attainment of normal levels for ≥2 lipid levels. Conclusions At least one dyslipidemia persisted in half of all patients and two-thirds of high cardiovascular risk patients treated with a statin. Dyslipidemias of HDL-C and/or triglycerides were as prevalent as elevated LDL-C among high cardiovascular risk patients. PMID:22566746

Biochemical modifications in Pinus pinaster Ait. as a result of environmental pollution.

PubMed

Acquaviva, Rosaria; Vanella, Luca; Sorrenti, Valeria; Santangelo, Rosa; Iauk, Liliana; Russo, Alessandra; Savoca, Francesca; Barbagallo, Ignazio; Di Giacomo, Claudia

2012-11-01

Exposure to chemical pollution can cause significant damage to plants by imposing conditions of oxidative stress. Plants combat oxidative stress by inducing antioxidant metabolites, enzymatic scavengers of activated oxygen and heat shock proteins. The accumulation of these proteins, in particular heat shock protein 70 and heme oxygenase, is correlated with the acquisition of thermal and chemical adaptations and protection against oxidative stress. In this study, we used Pinus pinaster Ait. collected in the areas of Priolo and Aci Castello representing sites with elevated pollution and reference conditions, respectively. The presence of heavy metals and the levels of markers of oxidative stress (lipid hydroperoxide levels, thiol groups, superoxide dismutase activity and expression of heat shock protein 70, heme oxygenase and superoxide dismutase) were evaluated, and we measured in field-collected needles the response to environmental pollution. P. pinaster Ait. collected from a site characterized by industrial pollution including heavy metals had elevated stress response as indicated by significantly elevated lipid hydroperoxide levels and decreased thiol groups. In particular, we observed that following a chronic chemical exposure, P. pinaster Ait. showed significantly increased expression of heat shock protein 70, heme oxygenase and superoxide dismutase. This increased expression may have protective effects against oxidative stress and represents an adaptative cellular defence mechanism. These results suggest that evaluation of heme oxygenase, heat shock protein 70 and superoxide dismutase expression in P. pinaster Ait. could represent a useful tool for monitoring environmental contamination of a region and to better understand mechanisms involved in plant defence and stress tolerance.

Compartmentalization of endocannabinoids into lipid rafts in a microglial cell line devoid of caveorrlin-1

PubMed Central

Rimmerman, Neta; Bradshaw, Heather B; Kozela, Ewa; Levy, Rivka; Juknat, Ana; Vogel, Zvi

2012-01-01

BACKGROUND AND PURPOSE N-acyl ethanolamines (NAEs) and 2-arachidonoyl glycerol (2-AG) are endogenous cannabinoids and along with related lipids are synthesized on demand from membrane phospholipids. Here, we have studied the compartmentalization of NAEs and 2-AG into lipid raft fractions isolated from the caveolin-1-lacking microglial cell line BV-2, following vehicle or cannabidiol (CBD) treatment. Results were compared with those from the caveolin-1-positive F-11 cell line. EXPERIMENTAL APPROACH BV-2 cells were incubated with CBD or vehicle. Cells were fractionated using a detergent-free continuous OptiPrep density gradient. Lipids in fractions were quantified using HPLC/MS/MS. Proteins were measured using Western blot. KEY RESULTS BV-2 cells were devoid of caveolin-1. Lipid rafts were isolated from BV-2 cells as confirmed by co-localization with flotillin-1 and sphingomyelin. Small amounts of cannabinoid CB1 receptors were found in lipid raft fractions. After incubation with CBD, levels and distribution in lipid rafts of 2-AG, N-arachidonoyl ethanolamine (AEA), and N-oleoyl ethanolamine (OEA) were not changed. Conversely, the levels of the saturated N-stearoyl ethanolamine (SEA) and N-palmitoyl ethanolamine (PEA) were elevated in lipid raft fractions. In whole cells with growth medium, CBD treatment increased AEA and OEA time-dependently, while levels of 2-AG, PEA and SEA did not change. CONCLUSIONS AND IMPLICATIONS Whereas levels of 2-AG were not affected by CBD treatment, the distribution and levels of NAEs showed significant changes. Among the NAEs, the degree of acyl chain saturation predicted the compartmentalization after CBD treatment suggesting a shift in cell signalling activity. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21449981

Metabolic Evidence of Diminished Lipid Oxidation in Women With Polycystic Ovary Syndrome

PubMed Central

Whigham, Leah D.; Butz, Daniel E.; Dashti, Hesam; Tonelli, Marco; Johnson, LuAnn K.; Cook, Mark E.; Porter, Warren P.; Eghbalnia, Hamid R.; Markley, John L.; Lindheim, Steven R.; Schoeller, Dale A.; Abbott, David H.; Assadi-Porter, Fariba M.

2014-01-01

Polycystic ovary syndrome (PCOS), a common female endocrinopathy, is a complex metabolic syndrome of enhanced weight gain. The goal of this pilot study was to evaluate metabolic differences between normal (n=10) and PCOS (n=10) women via breath carbon isotope ratio, urinary nitrogen and nuclear magnetic resonance (NMR)-determined serum metabolites. Breath carbon stable isotopes measured by cavity ring down spectroscopy (CRDS) indicated diminished (p<0.030) lipid use as a metabolic substrate during overnight fasting in PCOS compared to normal women. Accompanying urinary analyses showed a trending correlation (p<0.057) between overnight total nitrogen and circulating testosterone in PCOS women, alone. Serum analyzed by NMR spectroscopy following overnight, fast and at 2 h following an oral glucose tolerance test showed that a transient elevation in blood glucose levels decreased circulating levels of lipid, glucose and amino acid metabolic intermediates (acetone, 2-oxocaporate, 2-aminobutyrate, pyruvate, formate, and sarcosine) in PCOS women, whereas the 2 h glucose challenge led to increases in the same intermediates in normal women. These pilot data suggest that PCOS-related inflexibility in fasting-related switching between lipid and carbohydrate/protein utilization for carbon metabolism may contribute to enhanced weight gain. PMID:24765590

Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism.

PubMed

Klipping, Christine; Marr, Joachim

2005-06-01

To compare the effect of ethinyl estradiol 20 microg/drospirenone 3 mg (EE 20 microg/DRSP 3 mg) administered according to a 24/4 regimen with ethinyl estradiol 20 microg/desogestrel 150 microg (EE 20 microg/DSG 150 microg) administered according to the conventional 21/7 regimen on lipid, carbohydrate and hemostatic parameters. In this open-label study, healthy women were randomized to EE 20 microg/DRSP 3 mg or EE 20 microg/DSG 150 microg for seven cycles. Mean differences in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels at cycle 7 compared to baseline were assessed. Secondary variables included changes in other lipid, hemostatic and carbohydrate parameters. Both treatments increased HDL-cholesterol, but decreased LDL-cholesterol by a comparable extent. Although slightly elevated in both groups, blood glucose and C-peptide levels measured during oral glucose tolerance tests were within normal reference ranges at cycle 7. Overall, the differences in lipid, hemostatic or carbohydrate parameters were not significant between the two treatments. EE 20 microg/DRSP 3 mg has a good safety profile comparable with EE 20 microg/DSG 150 microg.

Dietary phytic acid prevents fatty liver by reducing expression of hepatic lipogenic enzymes and modulates gut microflora in rats fed a high-sucrose diet.

PubMed

Sekita, Ayaka; Okazaki, Yukako; Katayama, Tetsuyuki

2016-06-01

The aim of this study was to investigate the effect of phytic acid (PA) on fatty liver and gut microflora in rats fed a high-sucrose (HSC) diet. Three groups of rats were fed a high-starch (HSR) diet or an HSC diet with or without 1.02% sodium PA for 12 d. We evaluated hepatic weight, total lipids, and triacylglycerol (TG) levels, the activities and expression of hepatic lipogenic enzymes (glucose-6-phosphate dehydrogenase, malic enzyme 1, and fatty acid synthetase), and fecal microflora. The HSC diet significantly increased hepatic total lipids and TG levels, and the activities and expression of the hepatic lipogenic enzymes compared with the HSR diet. These upregulations were clearly suppressed by dietary PA. Consumption of PA elevated the fecal ratio of Lactobacillus spp. and depressed the ratio of Clostridium cocoides, and suppressed the elevation in the ratio of C. leptum induced by the HSC diet. This work showed that dietary PA ameliorates sucrose-induced fatty liver through reducing the expression of hepatic lipogenesis genes and modulates gut microflora in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemopreventive effect of bacoside A on N-nitrosodiethylamine-induced hepatocarcinogenesis in rats.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Ravisankar, Baskaran; Parthasarathy, Chandrakesan

2010-05-01

Chemoprevention is an effective approach to control hepatocarcinogenesis. Bacoside A, the active constituent of Bacopa monniera Linn., is anticipated to play a role in chemoprevention of liver cancer. In the present study, we investigated the chemopreventive effect of bacoside A against N-nitrosodiethylamine-induced hepatocarcinogenesis in an animal model. Administration of carcinogen showed a significant elevation in the levels of lipid peroxidation, serum tumor marker enzymes and liver injury marker enzymes with subsequent decrease in the levels of both hemolysate and liver antioxidant status. Bacoside A co-treatment maintained the N-nitrosodiethylamine-induced alterations at near normal level. Histopathological and electron microscopic study of the liver tissue also supports the above biochemical observations. From our findings we conclude that bacoside A is effective to prevent DEN-induced hepatocellular carcinoma by quenching lipid peroxidation and enhancing antioxidant status through free radical scavenging mechanism and having potential of protecting endogenous enzymatic and non-enzymatic antioxidant activity.

Impact of mitochondrial alternative oxidase expression on the response of Nicotiana tabacum to cold temperature.

PubMed

Wang, Jia; Rajakulendran, Nirusan; Amirsadeghi, Sasan; Vanlerberghe, Greg C

2011-08-01

The plant mitochondrial electron transport chain (ETC) includes a non-energy conserving alternative oxidase (AOX) thought to dampen reactive oxygen species (ROS) generation by the ETC and/or facilitate carbon metabolism by uncoupling it from ATP turnover. When wild-type (WT) Nicotiana tabacum grown at 28°C/22°C (light/dark) were transferred to 12°C/5°C, they showed a large induction of leaf Aox1a mRNA and AOX protein within 24 h. Transfer to cold also resulted in a large accumulation of monosaccharides, an increase in transcript level of genes encoding important ROS-scavenging enzymes and a moderate increase in lipid peroxidation. Transgenic plants with suppressed AOX level showed less cold-induced sugar accumulation than WT while transgenic plants with enhanced AOX levels showed enhanced sugar accumulation. This is inconsistent with the hypothesis that AOX acts to burn excess carbohydrate, but rather suggests a role for AOX to aid sugar accumulation, at least during cold stress. At 28°C/22°C, plants with suppressed AOX had elevated levels of lipid peroxidation compared with WT, while plants with enhanced AOX had reduced lipid peroxidation. This is consistent with the hypothesis that AOX dampens ROS generation and oxidative damage. However, this inverse relationship between AOX level and lipid peroxidation did not hold upon shift to cold. Under this stress condition, plants with strong suppression of AOX show enhanced induction of ROS-scavenging enzymes compared with WT and decline in lipid peroxidation. These data suggest that, under stress conditions, the lack of AOX enhances a mitochondrial stress-signaling pathway able to increase the ROS-scavenging capacity of the cell. Copyright © Physiologia Plantarum 2011.

Lipid reserve dynamics and magnification of persistent organic pollutants in spawning sockeye salmon (Oncorhynchus nerka) from the Fraser River, British Columbia.

PubMed

Kelly, Barry C; Gray, Samantha L; Ikonomou, Michael G; Macdonald, J Steve; Bandiera, Stelvio M; Hrycay, Eugene G

2007-05-01

Pacific sockeye salmon (Oncorhynchus nerka) can travel several hundred kilometers to reach native spawning grounds and fulfill semelparous reproduction. The dramatic changes in lipid reserves during upstream migration can greatly affect internal toxicokinetics of persistent organic pollutants (POPs) such as PCBs, PCDDs, and PCDFs. We measured lipid content changes and contaminant concentrations in tissues (liver, muscle, roe/gonads) and biomarker responses (ethoxyresorufin O-deethylase or EROD activity and CYP1A levels) in two Pacific sockeye salmon stocks sampled at several locations along their spawning migration in the Fraser River, British Columbia. Muscle lipid contents declined significantly with increasing upstream migration distance and corresponded to elevated lipid normalized concentrations of PCBs and PCDD/Fs in spawning sockeye. Post-migration magnification factors (MFs) in spawning sockeye ranged between 3 and 12 and were comparable to model-predicted MFs. sigmaPCBs(150-500 ng x g(-1) lipid), sigmaPCDD/Fs (1-1000 pg x g(-1) lipid) and 2,3,7,8-TCDD toxic equivalent or TEQ levels (0.1-15 pg x g(-1) lipid) in spawning sockeye were relatively low and did not affect hepatic EROD activity/CYP1A induction. Despite a 3-fold magnification, TEQ levels in eggs of spawning Fraser River sockeye did not exceed 0.3 pg x g(-1) wet wt, a threshold level associated with 30% egg mortality in salmonids. PCBs in Fraser River sockeye are comparable to previous levels in Pacific sockeye. In contrast to Pacific sockeye from more remote coastal locations, PCDDs and PCDFs in Fraser River sockeye were generally minor components (<25%) of TEQ levels, compared to dioxin like PCB contributions (>75%). The data suggest that (i) the Fraser River is not a major contamination source of PCBs or PCDD/Fs and (ii) marine contaminant distribution, food-chain dynamics, and ocean-migration pathway are likely important factors controlling levels and patterns of POPs in returning Pacific sockeye. We estimate an annual chemical flux entering the Fraser River of up to 150 g for sigmaPCBs and 40 mg for sigmaPCDD/ Fs via returning sockeye. The results indicate that historical concentrations of PCBs and PCDD/Fs remain a potential threat to organism and ecosystem health on the west coast of Canada.

Risk of type 2 diabetes mellitus associated with plasma lipid levels: The rural Chinese cohort study.

PubMed

Zhang, Ming; Zhou, Junmei; Liu, Yu; Sun, Xizhuo; Luo, Xinping; Han, Chengyi; Zhang, Lu; Wang, Bingyuan; Ren, Yongcheng; Zhao, Yang; Zhang, Dongdong; Liu, Xuejiao; Hu, Dongsheng

2018-01-01

To investigate the association of type 2 diabetes mellitus (T2DM) risk and plasma lipid levels in rural Chinese. Each lipid variable was divided into quartiles and dichotomized by clinical cutoff points. Cox proportional-hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of T2DM risk and plasma lipid levels and explore the interaction between plasma lipid levels and other risk factors. 11,929 participants were included in the analysis. We documented 720 incident cases of T2DM over 70,720.84 person-years of follow-up, for an incidence of 10.18/1,000 person-years. In the multivariable-adjusted model, risk of T2DM was increased with the highest versus lowest quartiles of total cholesterol (TC) and triglycerides (TG) levels and TC/high-density lipoprotein-cholesterol (HDL-C) and TG/HDL-C ratios. The HRs (95% CIs) for the fourth quartiles, for example, were 1.34 (1.03-1.74), 2.32 (1.73-3.13), 1.66 (1.23-2.25), and 1.84 (1.38-2.45), respectively. In addition, risk of T2DM was increased with high TG level and TC/HDL-C and TG/HDL-C ratios by clinical cutoffs. The HRs (95% CIs) were 1.50 (1.25-1.80), 1.24 (1.03-1.48), and 1.44 (1.18-1.75), respectively. Risk of T2DM was associated with interactions between all lipid variables and age and BMI. TG level and TG/HDL-C ratio additionally interacted with gender (all P interaction  < 0.0001). Risk of T2DM was increased with elevated serum levels of TC and TG and TC/HDL-C and TG/HDL-C ratios and also with interactions between high TC and TG levels and TC/HDL-C and TG/HDL-C ratios and age and BMI in a rural Chinese population. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-Water-Suppressed 1H MR Spectroscopy with Orientational Prior Knowledge Shows Potential for Separating Intra- and Extramyocellular Lipid Signals in Human Myocardium.

PubMed

Fillmer, Ariane; Hock, Andreas; Cameron, Donnie; Henning, Anke

2017-12-04

Conditions such as type II diabetes are linked with elevated lipid levels in the heart, and significantly increased risk of heart failure; however, metabolic processes underlying the development of cardiac disease in type II diabetes are not fully understood. Here we present a non-invasive method for in vivo investigation of cardiac lipid metabolism: namely, IVS-McPRESS. This technique uses metabolite-cycled, non-water suppressed 1 H cardiac magnetic resonance spectroscopy with prospective and retrospective motion correction. High-quality IVS-McPRESS data acquired from healthy volunteers allowed us to investigate the frequency shift of extramyocellular lipid signals, which depends on the myocardial fibre orientation. Assuming consistent voxel positioning relative to myofibres, the myofibre angle with the magnetic field was derived from the voxel orientation. For separation and individual analysis of intra- and extramyocellular lipid signals, the angle myocardial fibres in the spectroscopy voxel take with the magnetic field should be within ±24.5°. Metabolite and lipid concentrations were analysed with respect to BMI. Significant correlations between BMI and unsaturated fatty acids in intramyocellular lipids, and methylene groups in extramyocellular lipids were found. The proposed IVS-McPRESS technique enables non-invasive investigation of cardiac lipid metabolism and may thus be a useful tool to study healthy and pathological conditions.

[Study on the dynamic variations and influencing factors of serum lipid levels during pregnancy and postpartum].

PubMed

Xu, D; Liang, C; Chen, L; Wu, X D; He, J

2018-04-25

Objective: To study the variations and influencing factors of serum triglycerides and cholesterol levels during pregnancy and postpartum. Methods: A retrospective study was performed among 5 020 healthy singleton (95.10%, 4 774/5 020) and twin (4.90%, 246/5 020) women who had delivery in Women's Hospital, Zhejiang University School of Medicine from January 2011 to December 2016. Serum triglycerides and cholesterol levels during pregnancy and postpartum of all the cases were collected. Both singleton and twin pregnant women were divided into advanced age and appropriate age groups, and then data of serum sample were assigned to 3 groups according to the gestation weeks, which were second trimester pregnancy (24-28 gestation weeks) , third trimester pregnancy (32-41 gestation weeks) and postpartum (within 72 hours after delivery) . The serum triglycerides and cholesterol levels in each groups were compared. Results: (1) Serum triglycerides and cholesterol levels during the second trimester pregnancy, third trimester pregnancy and postpartum were higher than levels of non-pregnancy in both singleton and twin groups (all P< 0.05) . (2) Serum triglycerides and cholesterol levels in the third trimester pregnancy group were higher than those of second trimester pregnancy group in both advanced age and appropriate aged women regardless singleton or twin pregnancy (all P< 0.05) . The 95% CI of serum lipid levels in each group during second and third trimester pregnancy were as follows: in appropriate aged singleton group, the triglycerides levels were 1.07-4.13 and 1.52-7.21 mmol/L, and the cholesterol levels were 2.77-12.11 and 4.44-9.36 mmol/L. In advanced aged singleton group, the triglycerides levels were 1.28-4.61 and 1.70-7.80 mmol/L, and the cholesterol levels were 4.35-8.40 and 4.46-9.35 mmol/L; in appropriate aged twin group, the triglycerides levels were 1.39-7.16 and 1.90-9.29 mmol/L, and the cholesterol levels were 4.99-12.16 and 4.52-10.07 mmol/L; in advanced aged twin group, the triglycerides levels were 1.61-5.32 and 1.94-9.29 mmol/L, and the cholesterol levels were 5.24-8.10 and 4.53-8.86 mmol/L. (3) Serum lipids levels rapidly decreased during postpartum compared to the third trimester pregnancy. The 95% CI of blood lipid levels in each group were as follows: in appropriate aged singleton group, the triglycerides level was 0.90-5.64 mmol/L and the cholesterol level was 4.70-8.52 mmol/L; in advanced aged singleton group, the triglycerides level was 0.87-5.43 mmol/L and the cholesterol level was 4.68-9.04 mmol/L; in appropriate aged twin group, the triglycerides level was 1.20-8.21 mmol/L and the cholesterol level was 4.66-8.45 mmol/L; in advanced aged twin group, the triglycerides level was 1.32-6.61 mmol/L, and the cholesterol level was 5.01-7.94 mmol/L. (4) Serum triglycerides and cholesterol levels in twin pregnant women were significantly higher than in singleton during the second trimester and third trimester pregnancy both in advanced age and appropriate age groups (all P< 0.05) . During postpartum, there was no difference in serum lipid levels between the singleton and twin pregnant women in appropriate age group (triglycerides: P= 0.982; cholesterol: P= 0.759, respectively) . While the serum lipid levels in twin pregnant women were significantly higher than those of singleton women in advanced age group (triglycerides: P= 0.000; cholesterol: P= 0.000, respectively) . Conclusions: The standard of serum lipid levels of non-pregnant adults is not suitable for assessing that in pregnant women. Regardless of singleton or twin pregnancy, serum triglyceride and cholesterol levels during pregnancy elevate with the increasing gestational week and then rapidly decrease during postpartum. Age and twins are the influencing factors of the elevated physiological lipid levels during pregnancy.

mTORC2 Promotes Tumorigenesis via Lipid Synthesis.

PubMed

Guri, Yakir; Colombi, Marco; Dazert, Eva; Hindupur, Sravanth K; Roszik, Jason; Moes, Suzette; Jenoe, Paul; Heim, Markus H; Riezman, Isabelle; Riezman, Howard; Hall, Michael N

2017-12-11

Dysregulated mammalian target of rapamycin (mTOR) promotes cancer, but underlying mechanisms are poorly understood. We describe an mTOR-driven mouse model that displays hepatosteatosis progressing to hepatocellular carcinoma (HCC). Longitudinal proteomic, lipidomics, and metabolomic analyses revealed that hepatic mTORC2 promotes de novo fatty acid and lipid synthesis, leading to steatosis and tumor development. In particular, mTORC2 stimulated sphingolipid (glucosylceramide) and glycerophospholipid (cardiolipin) synthesis. Inhibition of fatty acid or sphingolipid synthesis prevented tumor development, indicating a causal effect in tumorigenesis. Increased levels of cardiolipin were associated with tubular mitochondria and enhanced oxidative phosphorylation. Furthermore, increased lipogenesis correlated with elevated mTORC2 activity and HCC in human patients. Thus, mTORC2 promotes cancer via formation of lipids essential for growth and energy production. Copyright © 2017 Elsevier Inc. All rights reserved.

Genetics of Lipid and Lipoprotein Disorders and Traits.

PubMed

Dron, Jacqueline S; Hegele, Robert A

2016-01-01

Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components. Recent advances in genetics of plasma lipids and lipoproteins include the following: (1) expanding the range of genes causing monogenic dyslipidemias, particularly elevated LDL cholesterol; (2) appreciating the role of polygenic effects in such traits as familial hypercholesterolemia and combined hyperlipidemia; (3) accumulating a list of common variants that determine plasma lipids and lipoproteins; (4) applying exome sequencing to identify collections of rare variants determining plasma lipids and lipoproteins that via Mendelian randomization have also implicated gene products such as NPC1L1 , APOC3 , LDLR , APOA5 , and ANGPTL4 as causal for atherosclerotic cardiovascular disease; and (5) using naturally occurring genetic variation to identify new drug targets, including inhibitors of apolipoprotein (apo) C-III, apo(a), ANGPTL3, and ANGPTL4. Here, we compile this disparate range of data linking human genetic variation to plasma lipids and lipoproteins, providing a "one stop shop" for the interested reader.

The boosted biomass and lipid accumulation in Chlorella vulgaris by supplementation of synthetic phytohormone analogs.

PubMed

Liu, Tingting; Liu, Fei; Wang, Chao; Wang, Zhenyao; Li, Yuqin

2017-05-01

This study attempted at maximizing biomass and lipid accumulation in Chlorella vulgaris by supplementation of natural abscisic acid (ABA) or synthetic 2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthaleneacetic acid (NAA) hormone analogs. Amongst three tested additives, NAA-treatment performed remarkable promoting effect on cell growth and lipid biosynthesis. The favorable lipid productivity (418.6mg/L/d) of NAA-treated cells showed 1.48 and 2.24 times more than that of 2,4-D and ABA. NAA-treatment also positively modified the proportions of saturated (C16:0 and C18:0) and monounsaturated fatty acids (C18:1) which were prone to high-quality biofuels-making. Further, NAA-treatment manipulated endogenous phytohormones metabolism leading to the elevated levels of indole-3-acetic acid, jasmonic acid, and salicylic acid and such hormone accumulation might be indispensable for signal transduction in regulating cell growth and lipid biosynthesis in microalgae. In addition, the economic-feasibility and eco-friendly estimation of NAA additive indicated the higher possibilities in developing affordable and scalable microalgal lipids for biofuels. Copyright © 2017 Elsevier Ltd. All rights reserved.

PCDD/Fs and PCBs in seafood species from Moreton Bay, Queensland, Australia.

PubMed

Matthews, V; Päpke, O; Gaus, C

2008-01-01

Previous studies have identified elevated levels of polychlorinated dibenzo-p-dioxins (PCDDs) in sediments and megafauna (dugongs and green turtles) in the marine environment of southeast Queensland, Australia. Little information exists, however, regarding the levels of PCDDs, polychlorinated dibenzofurans (PCDFs) and related polychlorinated biphenyls (PCBs) in seafood from this area. This study aims to establish baseline information on PCDD/F and PCB contamination in a range of seafood species from Moreton Bay and to investigate contaminant variability due to harvesting season, size, habitat location and trophic level. In addition, different seafood extraction methods were tested to evaluate their impact on lipid yields and contaminant concentration. Overall, the median TEQ(DF&PCB) levels in seafood from Moreton Bay were elevated compared to background levels in Australian marine/estuarine and retail fish. However, TEQ(DF&PCB) levels of most seafood analysed were below the respective EU maximum limits. High inter- and intraspecies variability was observed, which could be partially attributed to differences in trophic level, season harvested and habitat location.

Using FLIM in the study of permeability barrier function of aged and young skin

NASA Astrophysics Data System (ADS)

Xu, P.; Choi, E. H.; Man, M. Q.; Crumrine, D.; Mauro, T.; Elias, P.

2006-02-01

Aged skin commonly is afflicted by inflammatory skin diseases or xerosis/eczema that can be triggered or exacerbated by impaired epidermal permeability barrier homeostasis. It has been previously described a permeability barrier defect in humans of advanced age (> 75 years), which in a murine analog >18 mos, could be attributed to reduced lipid synthesis synthesis. However, the functional abnormality in moderately aged mice is due not to decreased lipid synthesis, but rather to a specific defect in stratum corneum (SC) acidification causing impaired lipid processing processing. Endogenous Na +/H + antiporter (NHE1) level was found declined in moderately aged mouse epidermis. This acidification defect leads to perturbed permeability barrier homeostasis through more than one pathways, we addressed suboptimal activation of the essential, lipid-processing enzyme, β-glucocerebrosidase (BGC) is linked to elevated SC pH. Finally, the importance of the epidermis acidity is shown by the normalization of barrier function after exogenous acidification of moderately aged skin.

[Indicators of lipid peroxidation in the blood in hereditary predisposition to arteriosclerosis].

PubMed

Davidenkova, E F; Shafran, M G; Veksler, B M

1990-02-01

In members of the families whose parents had atherosclerosis complicated by macrofocal myocardial infarction or stroke, the serum level of lipid peroxidation products was correlated to enzymatic activity of neutrophil and red blood cells oxidation-antioxidation. In persons with hereditary predisposition to atherosclerosis both with clinical signs of atherosclerosis and phenotypically healthy against the control group there was elevated content of plasma acylhydroperoxides and hypoactivity of neutrophil myeloperoxidase. Determination of lipid peroxidation products by malonic dealdehyde showed this parameter to be higher in members of the families of the study group and in those with cardiovascular disorders. For those whose parents had atherosclerosis versus control subjects there were no differences in the activity of superoxide dismutase, glutation peroxidase and catalase in the blood red cells. Shifts in lipid peroxidation and activity of blood myeloperoxidase are identical in type and may represent a pathogenetic ling in formation of hereditary predisposition to cardiovascular disorders of atherosclerotic origin, the detection of which becomes feasible in a subclinical period.

Changes in liver PPARalpha mRNA expression in response to two levels of high-safflower-oil diets correlate with changes in adiposity and serum leptin in rats and mice.

PubMed

Hsu, Shan-Ching; Huang, Ching-jang

2007-02-01

The ligand-dependent transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) is known to be activated by common fatty acids and to regulate the expression of genes of various lipid oxidation pathways and transport. High-fat diets provide more fatty acids, which presumably could enhance lipid catabolism through up-regulation of PPARalpha signaling. However, high intake of fat could also lead to obesity. To examine PPARalpha signaling in high-fat feeding and obesity, this study examined the hepatic mRNA expression of PPARalpha and some of its target genes in Wistar rats and C57BL/6J mice fed two levels (20% or 30% wt/wt) of high-safflower-oil (SFO; oleic-acid-rich) diets until animals showed significantly higher body weight (13 weeks for rats and 22 weeks for mice) than those of control groups fed a 5% SFO diet. At the end of these respective feeding periods, only the rats fed 30% SFO and the mice fed 20% SFO among the two groups fed high-fat diets showed significantly higher body weight, white adipose tissue weight, serum leptin and mRNA expression of PPARalpha (P<.05) compared to the respective control groups. Despite elevated acyl-CoA (a PPARalpha target gene) protein and activity in both groups fed high-fat diets, the mRNA expression level of most PPARalpha target genes examined correlated mainly to PPARalpha mRNA levels and not to fat intake or liver lipid levels. The observation that the liver PPARalpha mRNA expression in groups fed high-fat diets was significantly higher only in obese animals with elevated serum leptin implied that obesity and associated hyperleptinemia might have a stronger impact than dietary SFO intake per se on PPARalpha-regulated mRNA expression in the liver.

Soybean GmMYB73 promotes lipid accumulation in transgenic plants

PubMed Central

2014-01-01

Background Soybean is one of the most important oil crops. The regulatory genes involved in oil accumulation are largely unclear. We initiated studies to identify genes that regulate this process. Results One MYB-type gene GmMYB73 was found to display differential expression in soybean seeds of different developing stages by microarray analysis and was further investigated for its functions in lipid accumulation. GmMYB73 is a small protein with single MYB repeat and has similarity to CPC-like MYB proteins from Arabidopsis. GmMYB73 interacted with GL3 and EGL3, and then suppressed GL2, a negative regulator of oil accumulation. GmMYB73 overexpression enhanced lipid contents in both seeds and leaves of transgenic Arabidopsis plants. Seed length and thousand-seed weight were also promoted. GmMYB73 introduction into the Arabidopsis try cpc double mutant rescued the total lipids, seed size and thousand-seed weight. GmMYB73 also elevated lipid levels in seeds and leaves of transgenic Lotus, and in transgenic hairy roots of soybean plants. GmMYB73 promoted PLDα1 expression, whose promoter can be bound and inhibited by GL2. PLDα1 mutation reduced triacylglycerol levels mildly in seeds but significantly in leaves of Arabidopsis plants. Conclusions GmMYB73 may reduce GL2, and then release GL2-inhibited PLDα1 expression for lipid accumulation. Manipulation of GmMYB73 may potentially improve oil production in legume crop plants. PMID:24655684

Mechanism of insulin resistance in normal pregnancy.

PubMed

Hodson, K; Man, C Dalla; Smith, F E; Thelwall, P E; Cobelli, C; Robson, S C; Taylor, R

2013-08-01

Normal pregnancy is associated with insulin resistance although the mechanism is not understood. Increased intramyocellular lipid is closely associated with the insulin resistance of type 2 diabetes and obesity, and the aim of this study was to determine whether this was so for the physiological insulin resistance of pregnancy. Eleven primiparous healthy pregnant women (age: 27-39 years, body mass index 24.0±3.1 kg/m2) and no personal or family history of diabetes underwent magnetic resonance studies to quantify intramyocellular lipid, plasma lipid fractions, and insulin sensitivity. The meal-related insulin sensitivity index was considerably lower in pregnancy (45.6±9.9 vs. 193.0±26.1; 10(-4) dl/kg/min per pmol/l, p=0.0002). Fasting plasma triglyceride levels were elevated 3-fold during pregnancy (2.3±0.2 vs. 0.8±0.1 mmol/l, p<0.01) and the low-density density lipoprotein fraction, responsible for fatty acid delivery to muscle and other tissues, was 6-fold elevated (0.75±0.43 vs. 0.12±0.09 mmol/l; p=0.001). However, mean intramyocellular lipid concentrations of the soleus muscle were not different during pregnancy (20.0±2.3 vs. 19.1±3.2 mmol/l, p=0.64). The pregnancy effect on muscle insulin resistance is distinct from that underlying type 2 diabetes. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of NS lactobacillus strains on lipid metabolism of rats fed a high-cholesterol diet

PubMed Central

2013-01-01

Background Elevated serum cholesterol level is generally considered to be a risk factor for the development of cardiovascular diseases which seriously threaten human health. The cholesterol-lowering effects of lactic acid bacteria have recently become an area of great interest and controversy for many researchers. In this study, we investigated the effects of two NS lactobacillus strains, Lactobacillus plantarum NS5 and Lactobacillus delbrueckii subsp. bulgaricus NS12, on lipid metabolism of rats fed a high cholesterol diet. Methods Thirty-two SD rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The NS lactobacillus treated groups received the high-cholesterol diet supplemented with Lactobacillus plantarum NS5 or Lactobacillus delbrueckii subsp. bulgaricus NS12 in drinking water. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat weights, serum and liver cholesterol and lipid levels, intestinal microbiota and liver mRNA expression levels related to cholesterol metabolism were analyzed. Liver lipid deposition and adipocyte size were evaluated histologically. Results Compared with rats fed a high cholesterol diet, serum total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B and free fatty acids levels were decreased and apolipoprotein A-I level was increased in NS5 or NS12 strain treated rats, and with no significant change in high-density lipoprotein cholesterol level. Liver cholesterol and triglyceride levels were also significantly decreased in NS lactobacillus strains treated groups. Meanwhile, the NS lactobacillus strains obviously alleviated hepatic injuries, decreased liver lipid deposition and reduced adipocyte size of high cholesterol diet fed rats. NS lactobacillus strains restored the changes in intestinal microbiota compositions, such as the increase in Bacteroides and the decrease in Clostridium. NS lactobacillus strains also regulated the mRNA expression levels of liver enzymes related to cholesterol metabolism, including the down regulation of acyl-CoA:cholesterol acyltransferase (ACAT) and the upregulation of cholesterol 7α-hydroxylase (CYP7A1). Conclusion This study suggested that the two NS lactobacillus strains may affect lipid metabolism and have cholesterol-lowering effects in rats fed a high cholesterol diet. PMID:23656797

Effect of a marathon run on serum lipoproteins, creatine kinase, and lactate dehydrogenase in recreational runners.

PubMed

Kobayashi, Yoshio; Takeuchi, Toshiko; Hosoi, Teruo; Yoshizaki, Hidekiyo; Loeppky, Jack A

2005-12-01

The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride level was significantly elevated postrace, then fell 30% below baseline 1 day after the run, and returned to baseline after 1 week. Total cholesterol responded less dramatically but with a similar pattern. High-density lipoprotein cholesterol remained significantly elevated and low-density lipoprotein cholesterol was transiently reduced for 3 days after the run. The total cholesterol/high-density cholesterol ratio was significantly lowered for 3 days. Serum lactate dehydrogenase activity significantly doubled postrace and then declined but remained elevated for 2 weeks. Serum creatine kinase activity peaked 24 hr after the run, with a 15-fold rise, and returned to baseline after 1 week. The rise of these enzymes reflects mechanically damaged muscle cells leaking contents into the interstitial fluid. It is concluded that a prolonged strenuous exercise bout in recreational runners, such as a marathon, produces beneficial changes in lipid blood profiles that are significant for only 3 days. However, muscle damage is also evident for 1 week or more from the dramatic and long-lasting effect on enzyme levels. Laboratory values for these runners were outside normal ranges for some days after the race.

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

PubMed Central

Aalto-Setälä, K; Bisgaier, C L; Ho, A; Kieft, K A; Traber, M G; Kayden, H J; Ramakrishnan, R; Walsh, A; Essenburg, A D; Breslow, J L

1994-01-01

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system. Images PMID:8163677

Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial dysfunction[S

PubMed Central

Alecu, Irina; Tedeschi, Andrea; Behler, Natascha; Wunderling, Klaus; Lamberz, Christian; Lauterbach, Mario A. R.; Gaebler, Anne; Ernst, Daniela; Van Veldhoven, Paul P.; Al-Amoudi, Ashraf; Latz, Eicke; Othman, Alaa; Kuerschner, Lars; Hornemann, Thorsten; Bradke, Frank; Thiele, Christoph; Penno, Anke

2017-01-01

1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in the plasma of patients with type 2 diabetes and hereditary sensory and autonomic neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very similar, suggesting the involvement of deoxySLs in the pathology of both diseases. However, very little is known about the biology of these lipids and the underlying pathomechanism. We synthesized an alkyne analog of 1-deoxysphinganine (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and localization of deoxySLs. Our results indicate that the metabolism of these lipids is restricted to only some lipid species and that they are not converted to canonical sphingolipids or fatty acids. Furthermore, exogenously added alkyne-doxSA [(2S,3R)-2-aminooctadec-17-yn-3-ol] localized to mitochondria, causing mitochondrial fragmentation and dysfunction. The induced mitochondrial toxicity was also shown for natural doxSA, but not for sphinganine, and was rescued by inhibition of ceramide synthase activity. Our findings therefore indicate that mitochondrial enrichment of an N-acylated doxSA metabolite may contribute to the neurotoxicity seen in diabetic neuropathy and HSAN1. Hence, we provide a potential explanation for the characteristic vulnerability of peripheral nerves to elevated levels of deoxySLs. PMID:27881717

Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia.

PubMed

Ricotta, Daniel N; Frishman, William

2012-01-01

Mipomersen is an antisense oligonucleotide inhibitor of apolipoprotein (apo) B-100 currently in phase 3 of development for the treatment of hyperlipidemia in patients with a high risk for cardiovascular disease. The drug acts by inhibiting the production of apoB-100, which is the structural core for all atherogenic lipids, including low-density lipoprotein cholesterol (LDL-C). The agent has been shown to produce significant reductions in LDL-C from baseline values compared with placebos. Clinical trials have demonstrated that mipomersen reduces LDL-C up to 44% in patients with familial hypercholesterolemia and patients with significantly elevated LDL despite taking maximum doses of statins. Unlike other medications that target apoB-100, such as microsomal triglyceride transfer proteins, mipomersen does not cause hepatic steatosis or intestinal steatosis and does not affect dietary fat absorption. Adverse side effects encountered with mipomersen include flu-like symptoms, injection site reactions, and elevated liver transaminases. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for patients who are at high cardiovascular risk, intolerant to statins, and/or not at target lipid levels despite maximum doses of statin therapy. Clinical outcome studies looking at cardiovascular disease end points still need to be done.

Silymarin inhibits adipogenesis in the adipocytes in grass carp Ctenopharyngodon idellus in vitro and in vivo.

PubMed

Xiao, Peizhen; Yang, Zhou; Sun, Jian; Tian, Jingjing; Chang, Zhiguang; Li, Xuexian; Zhang, Baotong; Ye, Yuantu; Ji, Hong; Yu, Ermeng; Xie, Jun

2017-12-01

In this study, two experiments were performed to explore the function of silymarin in adipogenesis in grass carp (Ctenopharyngodon idellus) using in vitro and in vivo models. In experiment 1, differentiated grass carp pre-adipocytes were treated with silymarin for 6 days. Treatment with 100 μg mL -1 silymarin (SM100 group) significantly reduced triglyceride accumulation at day 6. The adipogenic gene expression levels of PPARγ, C/EBPα, SREBP1c, FAS, SCD1, and LPL, and the protein expression level of PPARγ were significantly down-regulated in the SM100 group. Additionally, the SM100 group had significantly lower reactive oxygen species production and reduced glutathione contents compared with the control in vitro. In experiment 2, the juvenile grass carp (mean body weight= 27.4 ± 0.17 g) were fed six isonitrogenous and isocaloric diets in a factorial design containing 0, 100, or 200 mg kg -1 silymarin (SM0, SM100, SM200) associated with either 4 or 8% lipid levels (low lipid, LL, and high lipid, HL, respectively) for 82 days. The results demonstrated that dietary silymarin supplementation significantly reduced the elevated intraperitoneal fat index in grass carp fed with high-lipid diets, and the gene expression of adipogenesis (PPARγ, FAS) when supplemented with dietary silymarin was notably lower than when no silymarin was supplemented under the high-lipid diets. Thus, our data suggest that silymarin suppressed lipid accumulation in grass carp both in vitro and in vivo, and the effect might be due to an influence on the expression of adipogenesis factors and ROS production partly associated with effects on antioxidant capability.

Contaminant levels in fish tissue from San Francisco Bay

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fairey, R.; Taberski, K.

1995-12-31

Edible fish species were collected from thirteen locations throughout San Francisco Bay, during the spring of 1994, for determination of contaminants levels in muscle tissue. Species collected included white croaker, surfperch, leopard and brown smoothhound sharks, striped bass, white sturgeon and halibut Sixty six composite tissue samples were analyzed for the presence of PAHs, PCBs, pesticides, trace elements and dioxin/furans. The US EPA approach to assessing chemical contaminant data for fish tissue consumption was used for identifying the primary chemicals of concern. Six chemicals or chemical groups were found to exceed screening levels established using the US EPA approach. PCBsmore » (as total Aroclors) exceeded the screening level of 3 ppb in all sixty six tissue samples, with the highest concentrations (638 ppb) found near San Francisco`s industrial areas. Mercury was elevated (> 0.14 ppm) in forty of the sixty-six samples with the highest levels (1.26 ppm) occurring in shark muscle tissues. Concentrations of the organochlorine pesticides dieldrin, total chlordanes and total DDTs exceeded screening levels in a number of samples. Dioxin/furans (as TEQs) were elevated (above 0.15 ppt) in 16 of the 19 samples analyzed. Fish with high lipid content (croaker and surfperch) in their muscle tissue generally exhibited higher contaminant levels while fish with low lipid levels (halibut and shark) exhibited lower organic contaminant levels. Tissue samples taken from North Bay stations most often exhibited high levels of chemical contamination. The California Office of Health Hazard Assessment is currently evaluating the results of this study and has issued an interim Health Advisory concerning the human consumption of fish tissue from San Francisco Bay.« less

Lipid Supplement in the Cultural Condition Facilitates the Porcine iPSC Derivation through cAMP/PKA/CREB Signal Pathway

PubMed Central

Zhang, Wei; Wang, Hanning; Zhang, Shaopeng; Zhong, Liang; Wang, Yanliang; Pei, Yangli; Cao, Suying

2018-01-01

Large numbers of lipids exist in the porcine oocytes and early embryos and have the positive effects on their development, suggesting that the lipids may play an important role in pluripotency establishment and maintenance in pigs. However, the effects of lipids and their metabolites, such as fatty acids on reprogramming and the pluripotency gene expression of porcine-induced pluripotent stem cells (iPSCs), are unclear. Here, we generated the porcine iPSCs that resemble the mouse embryonic stem cells (ESCs) under lipid and fatty-acid-enriched cultural conditions (supplement of AlbuMAX). These porcine iPSCs show positive for the ESCs pluripotency markers and have the differentiation abilities to all three germ layers, and importantly, have the capability of aggregation into the inner cell mass (ICM) of porcine blastocysts. We further confirmed that lipid and fatty acid enriched condition can promote the cell proliferation and improve reprogramming efficiency by elevating cAMP levels. Interestingly, this lipids supplement promotes mesenchymal–epithelial transition (MET) through the cAMP/PKA/CREB signal pathway and upregulates the E-cadherin expression during porcine somatic cell reprogramming. The lipids supplement also makes a contribution to lipid droplets accumulation in the porcine iPSCs that resemble porcine preimplantation embryos. These findings may facilitate understanding of the lipid metabolism in porcine iPSCs and lay the foundation of bona fide porcine embryonic stem cell derivation. PMID:29419748

ADAM17_i33780A>G polymorphism interacts with dietary n-6 polyunsaturated fatty acids to modulate obesity risk in the genetics of lipid lowering drugs and diet network study

USDA-ARS?s Scientific Manuscript database

The disintegrin and metalloproteinase ADAM17, also known as tumor necrosis factor alpha converting enzyme, is expressed in adipocytes, and elevated levels of expression have been linked to obesity and insulin resistance. This study evaluated the association of six ADAM17 single nucleotide polymorphi...

[Association of lipid parameters with insulin resistance in different glycemic among the elderly population].

PubMed

Pang, S J; Man, Q Q; Song, S; Song, P K; Liu, Z; Li, Y Q; He, L; Zhao, W H; Zhang, J

2018-06-06

Objective: This study was to analyze the association of lipid parameters with insulin resistance of Chinese elderly population in different glycemic status. Methods: Data were from China National Chronic Diseases and Nutrition Survey (2015). A total of 15 535 participants aged 60 and above who had completed survey questionnaire, physical examination, fasting blood biochemistry and insulin measurements were included in this study. According to the American Diabetes Association (2010) criteria, the participants were divided into normal glucose regulation, pre-diabetes, newly-diagnosed diabetes and previously-diagnosed diabetes. Multivariable logistic regression was preformed to assess the effects of lipid parameters on insulin resistance in different glycemic among the elderly population. Results: The proportion of normal glucose regulation, pre-diabetes, newly-diagnosed diabetes and previously-diagnosed diabetes was 50.46% ( n =7 839), 22.19% ( n =3 448), 12.46% ( n =1 937) and 14.88% ( n =2 311), respectively. The risk of insulin resistance increased with the elevated per quartile of triglycerides (TG) ( OR= 1.48,95 %CI: 1.35-1.62), non-high-density lipoprotein cholesterol (Non-HDL)/HDL-C ( OR= 1.23, 95 %CI: 1.12-1.35) and TG/HDL-C ( OR= 1.50, 95 %CI: 1.36-1.65) and decreased with the elevated per quartile of HDL-C ( OR= 0.83, 95 %CI: 0.76-0.90) after multivariate adjustment among normal glucose regulation participants. As for pre-diabetes participants, the risk of insulin resistance increased with the elevated per quartile of TG ( OR= 1.26, 95 %CI: 1.14-1.39) and TG/HDL-C ( OR= 1.38, 95 %CI: 1.24-1.54) and decreased with the elevated per quartile of HDL-C ( OR= 0.79, 95 %CI: 0.71-0.87). The risk of insulin resistance increased with the elevated per quartiles of TG/HDL-C ( OR= 1.29, 95 %CI: 1.12-1.48) among newly-diagnosed diabetes. As for previously-diagnosed diabetes, the risk of insulin resistance increased with the elevated per quartile of TG, Non-HDL/HDL-C and TG/HDL-C with adjusted OR (95 %CI ) about 1.28 (1.16-1.41), 1.37(1.21-1.55) and 1.51 (1.33-1.72) repsectivley and decreased with the elevated per quartile of HDL-C ( OR= 0.77, 95 %CI: 0.67-0.87). Conclusion: The relationship between lipid parameters and insulin resistance presented diversely in different glycemic status. The elderly with normal glucose regulation and previously-diagnosed diabetes should pay close attention to the change of TG/HDL-C, TG, HDL-C and Non-HDL/HDL-C. As for prediabetes participants, the TG/HDL-C, TG and HDL-C level change should be focused.

Correlation of plasma and peritoneal diasylate clomipramine concentration with hemodynamic recovery after intralipid infusion in rabbits.

PubMed

Harvey, Martyn; Cave, Grant; Hoggett, Kerry

2009-02-01

Drug sequestration to an expanded plasma lipid phase has been proposed as a potential mechanism of action for lipid emulsions in lipophilic cardiotoxin overdose. The authors set out to document plasma and peritoneal diasylate clomipramine concentration after resuscitation with lipid emulsion in a rabbit model of clomipramine-induced hypotension. Twenty sedated mechanically ventilated New Zealand White rabbits were allocated to receive either 12 mL/kg 20% Intralipid or 12 mL/kg saline solution, following clomipramine infusion to 50% baseline mean arterial pressure (MAP). Hemodynamic parameters and serum clomipramine concentration were determined to 59 minutes. Peritoneal dialysis with 20% Intralipid or saline solution was evaluated for clomipramine concentration. Mean arterial pressure was greater in lipid-treated animals as assessed by repeated-measures analysis of variance (F[1,14] = 6.84; p = 0.020). Lipid infusion was associated with elevated plasma clomipramine concentration and reduced initial volume of distribution (Vd; 5.7 [+/-1.6] L/kg lipid vs. 15.9 [+/-7.2] L/kg saline; p = 0.0001). Peritoneal diasylate clomipramine concentration was greater in lipid-treated animals (366.2 [+/-186.2] microg/L lipid vs. 37.7 [+/-13.8] microg/L saline; p = 0.002). Amelioration of clomipramine-induced hypotension with lipid infusion is associated with reduced initial Vd and elevated plasma clomipramine concentration consistent with intravascular drug-lipid sequestration. Concomitant peritoneal dialysis with lipid emulsion enhances clomipramine extraction.

The effect of oral contraception on cardiometabolic risk factors in women with elevated androgen levels.

PubMed

Krysiak, Robert; Gilowska, Małgorzata; Okopień, Bogusław

2017-02-01

In unselected reproductive-aged women, use of combined estrogen-progestin oral contraceptive pills has been linked with an increased risk of vascular disease. The aim of this study was to investigate the effect of oral contraception on cardiometabolic risk factors in a population of women with hyperandrogenism. The study included 16 untreated women with elevated testosterone levels and 15 matched healthy women who were then treated with oral contraceptive pills containing ethinyl estradiol (30μg) and drospirenone (3mg). Plasma lipids, glucose homeostasis markers, circulating levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as urinary albumin-to-creatinine ratio (UACR) were assessed at baseline and after 12 weeks of treatment. Compared to healthy women, women with elevated androgen levels showed increased plasma levels of hsCRP, fibrinogen and homocysteine, as well as a higher value of UACR. Oral contraception reduced androgen levels only in hyperandrogenic women. In healthy women, ethinyl estradiol plus drospirenone increased plasma levels of insulin, hsCRP, fibrinogen and homocysteine, while in women with elevated androgen levels their effect was limited only to a small increase in hsCRP. Our results suggest that a deteriorating effect of oral contraceptive pills containing ethinyl estradiol and drospirenone in hyperandrogenic women is weaker than in healthy young women and that ethinyl estradiol/drospirenone combination therapy may be safely used in the former group of patients. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Efficacy of brown seaweed hot water extract against HCl-ethanol induced gastric mucosal injury in rats.

PubMed

Raghavendran, Hanumantha Rao Balaji; Sathivel, Arumugam; Devaki, Thiruvengadam

2004-04-01

Effect of pre-treatment with hot water extract of marine brown alga Sargassum polycystum C.Ag. (100 mg/kg body wt, orally for period of 15 days) on HCl-ethanol (150 mM of HCl-ethanol mixture containing 0.15 N HCl in 70% v/v ethanol given orally) induced gastric mucosal injury in rats was examined with respect to lipid peroxides, antioxidant enzyme status, acid/pepsin and glycoproteins in the gastric mucosa. The levels of lipid peroxides of gastric mucosa and volume, acidity of the gastric juice were increased with decreased levels of antioxidant enzymes and glycoproteins were observed in HCl-ethanol induced rats. The rats pre-treated with seaweed extract prior to HCl-ethanol induction reversed the depleted levels of antioxidant enzymes and reduced the elevated levels of lipid peroxides when compared with HCl-ethanol induced rats. The levels of glycoproteins and alterations in the gastric juice were also maintained at near normal levels in rats pre-treated with seaweed extract. The rats given seaweed extract alone did not show any toxicity, which was confirmed by histopathological studies. These results suggest that the seaweed extract contains some anti-ulcer agents, which may maintain the volume/acidity of gastric juice and improve the gastric mucosa antioxidant defense system against HCl-ethanol induced gastric mucosal injury in rats.

Imbalance of plasma amino acids, metabolites and lipids in patients with lysinuric protein intolerance (LPI).

PubMed

Kurko, Johanna; Tringham, Maaria; Tanner, Laura; Näntö-Salonen, Kirsti; Vähä-Mäkilä, Mari; Nygren, Heli; Pöhö, Päivi; Lietzen, Niina; Mattila, Ismo; Olkku, Anu; Hyötyläinen, Tuulia; Orešič, Matej; Simell, Olli; Niinikoski, Harri; Mykkänen, Juha

2016-09-01

Lysinuric protein intolerance (LPI [MIM 222700]) is an aminoaciduria with defective transport of cationic amino acids in epithelial cells in the small intestine and proximal kidney tubules due to mutations in the SLC7A7 gene. LPI is characterized by protein malnutrition, failure to thrive and hyperammonemia. Many patients also suffer from combined hyperlipidemia and chronic kidney disease (CKD) with an unknown etiology. Here, we studied the plasma metabolomes of the Finnish LPI patients (n=26) and healthy control individuals (n=19) using a targeted platform for analysis of amino acids as well as two analytical platforms with comprehensive coverage of molecular lipids and polar metabolites. Our results demonstrated that LPI patients have a dichotomy of amino acid profiles, with both decreased essential and increased non-essential amino acids. Altered levels of metabolites participating in pathways such as sugar, energy, amino acid and lipid metabolism were observed. Furthermore, of these metabolites, myo-inositol, threonic acid, 2,5-furandicarboxylic acid, galactaric acid, 4-hydroxyphenylacetic acid, indole-3-acetic acid and beta-aminoisobutyric acid associated significantly (P<0.001) with the CKD status. Lipid analysis showed reduced levels of phosphatidylcholines and elevated levels of triacylglycerols, of which long-chain triacylglycerols associated (P<0.01) with CKD. This study revealed an amino acid imbalance affecting the basic cellular metabolism, disturbances in plasma lipid composition suggesting hepatic steatosis and fibrosis and novel metabolites correlating with CKD in LPI. In addition, the CKD-associated metabolite profile along with increased nitrite plasma levels suggests that LPI may be characterized by increased oxidative stress and apoptosis, altered microbial metabolism in the intestine and uremic toxicity. Copyright © 2016 Elsevier Inc. All rights reserved.

The influence of coping with perceived racism and stress on lipid levels in African Americans.

PubMed

Mwendwa, Denee T; Sims, Regina C; Madhere, Serge; Thomas, Joneis; Keen, Larry D; Callender, Clive O; Campbell, Alfonso L

2011-07-01

Lipid dysregulation is a major contributor to cardiovascular disease (CVD) risk and is attributed to numerous biological, psychosocial, and behavioral risk factors. Psychological stress has been examined as a predictor of lipid dysregulation; however, the role of coping with perceived racism, a stressor unique to the African American experience, has not been addressed. The current study sought to determine the impact of behavioral coping responses to perceived racism and perceived daily stress on lipid levels in African Americans. The sample consisted of 122 African American participants who resided in the Washington, DC, metropolitan area. Data were collected as part of an ongoing study entitled Stress and Psychoneuroimmunological Factors in Renal Health and Disease at Howard University Hospital. Through canonical analysis, distinct profiles of African American lipid function emerged with body mass index, age, and behavioral coping responses to perceived racism being associated with high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), respectively. Results from linear regression analyses showed that greater endorsement of behavioral coping responses to perceived racism items predicted higher levels of LDL (B = .24, p < .05). This relationship was not mediated by pathophysiological mechanisms associated with the stress response system such as cortisol, norepinephrine, epinephrine, and IL-6. The relationship between elevated levels of LDL and behavioral coping responses to perceived racism suggests that African Americans may be at increased risk for CVD due to the unique stress encountered by racism in our culture. Behavioral pathways used to counteract the negative effects of perceived discrimination may better explain this relationship. Further research is necessary to determine other biobehavioral and pathophysiological mechanisms that explain this relationship.

The effect of cinnamon extract and long-term aerobic training on heart function, biochemical alterations and lipid profile following exhaustive exercise in male rats.

PubMed

Badalzadeh, Reza; Shaghaghi, Mehrnoush; Mohammadi, Mustafa; Dehghan, Gholamreza; Mohammadi, Zeynab

2014-12-01

Regular training is suggested to offer a host of benefits especially on cardiovascular system. In addition, medicinal plants can attenuate oxidative stress-mediated damages induced by stressor insults. In this study, we investigated the concomitant effect of cinnamon extract and long-term aerobic training on cardiac function, biochemical alterations and lipid profile following exhaustive exercise. Male Wistar rats (250-300 g) were divided into five groups depending on receiving regular training, cinnamon bark extraction, none or both of them, and then encountered with an exhausted exercise in last session. An 8-week endurance training program was designed with a progressive increase in training speed and time. Myocardial hemodynamics was monitored using a balloon-tipped catheter inserted into left ventricles. Blood samples were collected for analyzing biochemical markers, lipid profiles and lipid-peroxidation marker, malondealdehyde (MDA). Trained animals showed an enhanced cardiac force and contractility similar to cinnamon-treated rats. Co-application of regular training and cinnamon had additive effect in cardiac hemodynamic (P<0.05). Both regular training and supplementation with cinnamon significantly decreased serum levels of total cholesterol, low-density lipoprotein (LDL), and increased high-density lipoprotein (HDL) level and HDL/LDL ratio as compared to control group (P<0.01). Furthermore, pre-treatment with cinnamon extract and/or regular training significantly reduced MDA level elevation induced by exhausted exercise (P<0.01). Long-term treatment of rats with cinnamon and regular training improved cardiac hemodynamic through an additive effect. The positive effects of cinnamon and regular training on cardiac function were associated with a reduced serum MDA level and an improved blood lipid profile.

The Influence of Coping With Perceived Racism and Stress on Lipid Levels in African Americans

PubMed Central

Mwendwa, Denee T.; Sims, Regina C.; Madhere, Serge; Thomas, Joneis; Keen, Larry D.; Callender, Clive O.; Campbell, Alfonso L.

2016-01-01

Background Lipid dysregulation is a major contributor to cardiovascular disease (CVD) risk and is attributed to numerous biological, psychosocial, and behavioral risk factors. Psychological stress has been examined as a predictor of lipid dysregulation; however, the role of coping with perceived racism, a stressor unique to the African American experience, has not been addressed. The current study sought to determine the impact of behavioral coping responses to perceived racism and perceived daily stress on lipid levels in African Americans. Methods The sample consisted of 122 African American participants who resided in the Washington, DC, metropolitan area. Data were collected as part of an ongoing study entitled Stress and Psychoneuroimmunological Factors in Renal Health and Disease at Howard University Hospital. Results Through canonical analysis, distinct profiles of African American lipid function emerged with body mass index, age, and behavioral coping responses to perceived racism being associated with high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), respectively. Results from linear regression analyses showed that greater endorsement of behavioral coping responses to perceived racism items predicted higher levels of LDL (β = .24, p < .05). This relationship was not mediated by pathophysiological mechanisms associated with the stress response system such as cortisol, norepinephrine, epinephrine, and IL-6. Conclusion The relationship between elevated levels of LDL and behavioral coping responses to perceived racism suggests that African Americans may be at increased risk for CVD due to the unique stress encountered by racism in our culture. Behavioral pathways used to counteract the negative effects of perceived discrimination may better explain this relationship. Further research is necessary to determine other biobehavioral and pathophysiological mechanisms that explain this relationship. PMID:21999034

A relative quantitative positive/negative ion switching method for untargeted lipidomics via high resolution LC-MS/MS from any biological source

PubMed Central

Breitkopf, Susanne B.; Ricoult, Stéphane J. H.; Yuan, Min; Xu, Ying; Peake, David A.; Manning, Brendan D.

2017-01-01

Introduction Advances in high-resolution mass spectrometry have created renewed interest for studying global lipid biochemistry in disease and biological systems. Objectives Here, we present an untargeted 30 min. LC-MS/MS platform that utilizes positive/negative polarity switching to perform unbiased data dependent acquisitions (DDA) via higher energy collisional dissociation (HCD) fragmentation to profile more than 1000–1500 lipid ions mainly from methyl-tert-butyl ether (MTBE) or chloroform:methanol extractions. Methods The platform uses C18 reversed-phase chromatography coupled to a hybrid QExactive Plus/HF Orbitrap mass spectrometer and the entire procedure takes ~10 h from lipid extraction to identification/quantification for a data set containing 12 samples (~4 h for a single sample). Lipids are identified by both accurate precursor ion mass and fragmentation features and quantified using Lipid-Search and Elements software. Results Using this approach, we are able to profile intact lipid ions from up to 18 different main lipid classes and 66 subclasses. We show several studies from different biological sources, including cultured cancer cells, resected tissues from mice such as lung and breast tumors and biological fluids such as plasma and urine. Conclusions Using mouse embryonic fibroblasts, we showed that TSC2−/− KD significantly abrogates lipid biosynthesis and that rapamycin can rescue triglyceride (TG) lipids and we show that SREBP−/− shuts down lipid biosynthesis significantly via mTORC1 signaling pathways. We show that in mouse EGFR driven lung tumors, a large number of TGs and phosphatidylmethanol (PMe) lipids are elevated while some phospholipids (PLs) show some of the largest decrease in lipid levels from ~ 2000 identified lipid ions. In addition, we identified more than 1500 unique lipid species from human blood plasma. PMID:28496395

The effects of the aqueous extract and residue of Matcha on the antioxidant status and lipid and glucose levels in mice fed a high-fat diet.

PubMed

Xu, Ping; Ying, Le; Hong, Gaojie; Wang, Yuefei

2016-01-01

Matcha is a kind of powdered green tea produced by grinding with a stone mill. In the present study, the preventive effects of the aqueous extract (water-soluble) and residue (water-insoluble) of Matcha on the antioxidant status and lipid and glucose levels in mice fed a high-fat diet were investigated. Mice were fed seven different experimental diets for 4 weeks: a normal diet control (NC), a high-fat diet (HF), a high-fat diet with 0.025% Matcha (MLD), a high-fat diet with 0.05% Matcha (MMD), a high-fat diet with 0.075% Matcha (MHD), a high-fat diet with 0.05% Matcha aqueous extracts (ME), and a high-fat diet with 0.05% Matcha residues (MR). It was found that serum total cholesterol (TC) and triglyceride (TG) levels of the MHD group were significantly decreased compared to those of the HF group. Furthermore, in the MHD group, the level of high-density lipoprotein-cholesterol (HDL-C) was elevated, on the contrary the level of low-density lipoprotein-cholesterol (LDL-C) was suppressed. Moreover, Matcha could significantly lower the blood glucose levels, and improve the superoxide dismutase (SOD) activity and malondialdehyde (MAD) contents both in serum and liver; besides, the serum GSH-Px activity indicated that the oxidative stress caused by HF could be reversed by administration of Matcha. These findings suggest that Matcha has beneficial effects through the suppression of the blood glucose (BG) accumulation and promotion of the lipid metabolism and antioxidant activities. Moreover, the water-insoluble part of Matcha is suggested to play an important role in the suppression of diet-induced high levels of lipid and glucose.

Trans-4-oxo-2--nonenal potently alters mitochondrial function

USDA-ARS?s Scientific Manuscript database

Alzheimer’s disease elevates lipid peroxidation in the brain and data indicate that lipid-aldehydes are pathological effectors of lipid peroxidation. The disposition of 4-substituted nonenals derived from arachidonate (20:4, n-6) and linoleate (18:2, n-6) oxidation is modulated by their protein addu...

Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization

PubMed Central

Bates, Ryan C.; Fees, Colby P.; Holland, William L.; Winger, Courtney C.; Batbayar, Khulan; Ancar, Rachel; Bergren, Todd; Petcoff, Douglas; Stith, Bradley J.

2014-01-01

We report a new step in the fertilization in Xenopus laevis which has been found to involve activation of Src tyrosine kinase to stimulate phospholipase C-γ (PLC- γ) which increases inositol 1,4,5-trisphosphate (IP3) to release intracellular calcium ([Ca]i). Molecular species analysis and mass measurements suggested that sperm activate phospholipase D (PLD) to elevate phosphatidic acid (PA). We now report that PA mass increased 2.7 fold by 1 minute after insemination and inhibition of PA production by two methods inhibited activation of Src and PLCγ, increased [Ca]i and other fertilization events. As compared to 14 other lipids, PA strongly bound Xenopus Src but not PLCγ. Addition of synthetic PA activated egg Src (an action requiring intact lipid rafts) and PLCγ as well as doubling the amount of PLCγ in rafts. In the absence of elevated [Ca]i, PA addition elevated IP3 mass to levels equivalent to that induced by sperm (but twice that achieved by calcium ionophore). Finally, PA induced [Ca]i release that was blocked by an IP3 receptor inhibitor. As only PLD1b message was detected, and Western blotting did not detect PLD2, we suggest that sperm activate PLD1b to elevate PA which then binds to and activates Src leading to PLCγ stimulation, IP3 elevation and [Ca]i release. Due to these and other studies, PA may also play a role in membrane fusion events such as sperm-egg fusion, cortical granule exocytosis, the elevation of phosphatidylinositol 4,5-bisphosphate and the large, late increase in sn 1,2-diacylglycerol in fertilization. PMID:24269904

Activation of Src and release of intracellular calcium by phosphatidic acid during Xenopus laevis fertilization.

PubMed

Bates, Ryan C; Fees, Colby P; Holland, William L; Winger, Courtney C; Batbayar, Khulan; Ancar, Rachel; Bergren, Todd; Petcoff, Douglas; Stith, Bradley J

2014-02-01

We report a new step in the fertilization in Xenopus laevis which has been found to involve activation of Src tyrosine kinase to stimulate phospholipase C-γ (PLC-γ) which increases inositol 1,4,5-trisphosphate (IP3) to release intracellular calcium ([Ca](i)). Molecular species analysis and mass measurements suggested that sperm activate phospholipase D (PLD) to elevate phosphatidic acid (PA). We now report that PA mass increased 2.7 fold by 1 min after insemination and inhibition of PA production by two methods inhibited activation of Src and PLCγ, increased [Ca](i) and other fertilization events. As compared to 14 other lipids, PA specifically bound Xenopus Src but not PLCγ. Addition of synthetic PA activated egg Src (an action requiring intact lipid rafts) and PLCγ as well as doubling the amount of PLCγ in rafts. In the absence of elevated [Ca](i), PA addition elevated IP3 mass to levels equivalent to that induced by sperm (but twice that achieved by calcium ionophore). Finally, PA induced [Ca](i) release that was blocked by an IP3 receptor inhibitor. As only PLD1b message was detected, and Western blotting did not detect PLD2, we suggest that sperm activate PLD1b to elevate PA which then binds to and activates Src leading to PLCγ stimulation, IP3 elevation and [Ca](i) release. Due to these and other studies, PA may also play a role in membrane fusion events such as sperm-egg fusion, cortical granule exocytosis, the elevation of phosphatidylinositol 4,5-bisphosphate and the large, late increase in sn 1,2-diacylglycerol in fertilization. © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Effect of n-3 polyunsaturated fatty acids on the lipidic profile of healthy Mexican volunteers.

PubMed

Carvajal, O; Angulo, O

1997-01-01

The effect of n-3 polyunsaturated fatty acids on the serum lipid profile in a Mexican population was evaluated. Three g of salmon oil was the daily intake during four weeks. Total cholesterol, triglycerides, low density lipoproteins, high density lipoproteins and erythrocyte fatty acid composition were analyzed. The hypertriglyceridemic group showed a statistically significant (p < 0.05) reduction of triglycerides and significant (p < 0.01) elevation of high density lipoproteins. The hypercholesterolemic group reduced significantly the levels of cholesterol and triglycerides; high density lipoproteins were augmented by 11.6%. The hypolipidemic effect of n-3 polyunsaturated fatty acids was manifest in the Mexican volunteers under the conditions here evaluated.

The Contribution of GWAS Loci in Familial Dyslipidemias

PubMed Central

Söderlund, Sanni; Surakka, Ida; Matikainen, Niina; Pirinen, Matti; Pajukanta, Päivi; Service, Susan K.; Laurila, Pirkka-Pekka; Ehnholm, Christian; Salomaa, Veikko; Wilson, Richard K.; Palotie, Aarno; Freimer, Nelson B.; Taskinen, Marja-Riitta; Ripatti, Samuli

2016-01-01

Familial combined hyperlipidemia (FCH) is a complex and common familial dyslipidemia characterized by elevated total cholesterol and/or triglyceride levels with over five-fold risk of coronary heart disease. The genetic architecture and contribution of rare Mendelian and common variants to FCH susceptibility is unknown. In 53 Finnish FCH families, we genotyped and imputed nine million variants in 715 family members with DNA available. We studied the enrichment of variants previously implicated with monogenic dyslipidemias and/or lipid levels in the general population by comparing allele frequencies between the FCH families and population samples. We also constructed weighted polygenic scores using 212 lipid-associated SNPs and estimated the relative contributions of Mendelian variants and polygenic scores to the risk of FCH in the families. We identified, across the whole allele frequency spectrum, an enrichment of variants known to elevate, and a deficiency of variants known to lower LDL-C and/or TG levels among both probands and affected FCH individuals. The score based on TG associated SNPs was particularly high among affected individuals compared to non-affected family members. Out of 234 affected FCH individuals across the families, seven (3%) carried Mendelian variants and 83 (35%) showed high accumulation of either known LDL-C or TG elevating variants by having either polygenic score over the 90th percentile in the population. The positive predictive value of high score was much higher for affected FCH individuals than for similar sporadic cases in the population. FCH is highly polygenic, supporting the hypothesis that variants across the whole allele frequency spectrum contribute to this complex familial trait. Polygenic SNP panels improve identification of individuals affected with FCH, but their clinical utility remains to be defined. PMID:27227539

Effects of chronic elevated ozone concentration on the redox state and fruit yield of red pepper plant Capsicum baccatum.

PubMed

Bortolin, Rafael Calixto; Caregnato, Fernanda Freitas; Divan, Armando Molina; Reginatto, Flávio Henrique; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

2014-02-01

Ozone (O3) is one of the most harmful air pollutants to crops, contributing to high losses on crop yield. Tropospheric O3 background concentrations have increased since pre-industrial times reaching phytotoxic concentrations in many world regions. Capsicum peppers are the second most traded spice in the world, but few studies concerning the O3 effects in this genus are known. Thereby, the aim of this work was to evaluate the effects of chronic exposure to elevated O3 concentrations in red pepper plant Capsicum baccatum L. var. pendulum with especial considerations on the leaf redox state and fruit yield. Fifteen C. baccatum plants were exposed to O3 in open-top chambers during fruit ripening (62 days) at a mean concentration of 171.6 µg/m(3) from 10:00 am to 4:00 pm. We found that O3 treated plants significantly decreased the amount and the total weight of fruits, which were probably a consequence of the changes on leaf oxidative status induced by ozone exposure. Ozone exposed plants increased the reactive oxygen species (ROS) levels on the leaves, which may be associated with the observed decrease on the activity of enzymatic antioxidant defense system, as well with lower levels of polyphenol and reduced thiol groups. Enhanced ROS production and the direct O3 reaction lead to biomacromolecules damages as seen in the diminished chlorophyll content and in the elevated lipid peroxidation and protein carbonylation levels. Through a correlation analysis it was possible to observe that polyphenols content was more important to protect pepper plants against oxidative damages to lipids than to proteins. © 2013 Published by Elsevier Inc.

Maternal Circulating Lipid Profile during Early Pregnancy: Racial/Ethnic Differences and Association with Spontaneous Preterm Delivery.

PubMed

Chen, Xinhua; Scholl, Theresa O; Stein, Thomas P; Steer, Robert A; Williams, Keith P

2017-01-01

Prior reports on the association between altered maternal serum lipid levels with preterm delivery are inconsistent. Ethnic differences in serum lipids during pregnancy and their relation to preterm delivery have not been studied. We examined the relationships of six maternal lipids during early pregnancy with the risk of spontaneous preterm delivery (SPTD). The design represents a case-control study nested within a large prospective, multiethnic cohort of young, generally healthy pregnant women. SPTD cases ( n = 183) and controls who delivered at term ( n = 376) were included. SPTD is defined as delivery at <37 completed weeks of gestation without indicated conditions. We found that African-American women had significantly increased levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (apoA1), and lower triglyceride (TG) and apolipoprotein B (apoB) levels compared to Hispanic and non-Hispanic Caucasians combined. Elevated HDL-C and apoA1 concentrations were significantly associated with an increased odds of SPTD after controlling for potential confounding factors. The adjusted odds ratio (AOR) was 1.91 (95% confidence interval (CI) 1.15, 3.20) for the highest quartile of HDL-C relative to the lowest quartile, and for apoA1 the AOR was 1.94 (95% CI 1.16, 3.24). When controlling for ethnicity, the results remained comparable. These data suggest that pregnant African-American women had a more favorable lipid profile suggestive of a reduction in cardiovascular risk. Despite this, increased HDL-C and apoA1 were both found to be associated with SPTD.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keith, Dove; Finlay, Liam; Butler, Judy

Highlights: • 24 month old rats were supplemented with 0.2% lipoic acid in the diet for 2 weeks. • Lipoic acid shifts phase of core circadian clock proteins. • Lipoic acid corrects age-induced desynchronized lipid metabolism rhythms. - Abstract: It is well established that lipid metabolism is controlled, in part, by circadian clocks. However, circadian clocks lose temporal precision with age and correlates with elevated incidence in dyslipidemia and metabolic syndrome in older adults. Because our lab has shown that lipoic acid (LA) improves lipid homeostasis in aged animals, we hypothesized that LA affects the circadian clock to achieve thesemore » results. We fed 24 month old male F344 rats a diet supplemented with 0.2% (w/w) LA for 2 weeks prior to sacrifice and quantified hepatic circadian clock protein levels and clock-controlled lipid metabolic enzymes. LA treatment caused a significant phase-shift in the expression patterns of the circadian clock proteins Period (Per) 2, Brain and Muscle Arnt-Like1 (BMAL1), and Reverse Erythroblastosis virus (Rev-erb) β without altering the amplitude of protein levels during the light phase of the day. LA also significantly altered the oscillatory patterns of clock-controlled proteins associated with lipid metabolism. The level of peroxisome proliferator-activated receptor (PPAR) α was significantly increased and acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) were both significantly reduced, suggesting that the LA-supplemented aged animals are in a catabolic state. We conclude that LA remediates some of the dyslipidemic processes associated with advanced age, and this mechanism may be at least partially through entrainment of circadian clocks.« less

Vitamin C attenuation of the development of type I diabetes mellitus by interferon-alpha.

PubMed

al-Zuhair, H; Mohamed, H E

1998-07-01

Interferon alpha (IFN-alpha) inhibits insulin release and may be cytotoxic to pancreatic islets. Increased free radical activity may be implicated in the cytotoxic action of IFN-alpha and development of diabetes mellitus. Therefore we measured markers of free radical activity (lipid peroxides and the non-peroxide-conjugated diene isomer of linoleic acid [PL-9,11-LA']) along with some pancreatic variables in male albino rats treated with IFN-alpha, as well as the possible protective effect of two antioxidants, vitamin C and mannitol. Compared to untreated rats, it was shown that IFN-alpha induced an increase in plasma glucose. Pancreatic and serum insulin, as well as serum C-peptide, were increased after 1 week, then their levels were reduced after 2 weeks. Plasma lipids peroxides and (PL-9,11-LA') were markedly elevated, while linoleic acid was reduced. These changes in the studied parameters were attributed, in part, to the superoxide and free radical generation during IFN-alpha treatment. Plasma glucagon was increased after 2 weeks. Administration of vitamin C along with IFN-alpha succeeded in modulating most of the altered parameters affected during IFN-alpha. The hyperglycaemic effect of IFN-alpha was greatly ameliorated and the negative effect on pancreatic and serum insulin and serum C-peptide were nearly abolished. The elevated levels of lipid peroxide and (PL-9,11-LA') and the reduction in linoleic acid being normalised. The only persistent effect was the increase in plasma glucagon. Concurrent administration of mannitol with IFN-alpha caused no changes in the parameters studied compared to that induced by treatment with IFN-alpha alone.

Effect of temperature on fatty acid metabolism in skeletal muscle mitochondria of untrained and endurance-trained rats.

PubMed

Zoladz, Jerzy A; Koziel, Agnieszka; Broniarek, Izabela; Woyda-Ploszczyca, Andrzej M; Ogrodna, Karolina; Majerczak, Joanna; Celichowski, Jan; Szkutnik, Zbigniew; Jarmuszkiewicz, Wieslawa

2017-01-01

We studied the effects of various assay temperatures, representing hypothermia (25°C), normothermia (35°C), and hyperthermia (42°C), on the oxidation of lipid-derived fuels in rat skeletal muscle mitochondria of untrained and endurance-trained rats. Adult 4-month-old male Wistar rats were assigned to a training group (rats trained on a treadmill for 8 weeks) or a sedentary control group. In skeletal muscle mitochondria of both control and trained rats, an increase in the assay temperature from 25°C to 42°C was accompanied by a consistent increase in the oxidation of palmitoylcarnitine and glycerol-3-phosphate. Moreover, endurance training increased mitochondrial capacity to oxidize the lipid-derived fuels at all studied temperatures. The endurance training-induced increase in mitochondrial capacity to oxidize fatty acids was accompanied by an enhancement of mitochondrial biogenesis, as shown by the elevated expression levels of Nrf2, PGC1α, and mitochondrial marker and by the elevated expression levels of mitochondrial proteins involved in fatty acid metabolism, such as fatty acid transporter CD36, carnitine palmitoyltransferase 1A (CPT1A), and acyl-CoA dehydrogenase (ACADS). We conclude that hyperthermia enhances but hypothermia attenuates the rate of the oxidation of fatty acids and glycerol-3-phosphate in rat skeletal muscle mitochondria isolated from both untrained and trained rats. Moreover, our results indicate that endurance training up-regulates mitochondrial biogenesis markers, lipid-sustained oxidative capacity, and CD36 and CPT1A proteins involved in fatty acid transport, possibly via PGC1α and Nrf2 signaling pathways.

Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

PubMed

Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

2016-03-01

A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

Physiological and Transcriptome Responses to Combinations of Elevated CO2 and Magnesium in Arabidopsis thaliana

PubMed Central

Niu, Yaofang; Ahammed, Golam Jalal; Tang, Caixian; Guo, Longbiao; Yu, Jingquan

2016-01-01

The unprecedented rise in atmospheric CO2 concentration and injudicious fertilization or heterogeneous distribution of Mg in the soil warrant further research to understand the synergistic and holistic mechanisms involved in the plant growth regulation. This study investigated the influence of elevated CO2 (800 μL L−1) on physiological and transcriptomic profiles in Arabidopsis cultured in hydroponic media treated with 1 μM (low), 1000 μM (normal) and 10000 μM (high) Mg2+. Following 7-d treatment, elevated CO2 increased the shoot growth and chlorophyll content under both low and normal Mg supply, whereas root growth was improved exclusively under normal Mg nutrition. Notably, the effect of elevated CO2 on mineral homeostasis in both shoots and roots was less than that of Mg supply. Irrespective of CO2 treatment, high Mg increased number of young leaf but decreased root growth and absorption of P, K, Ca, Fe and Mn whereas low Mg increased the concentration of P, K, Ca and Fe in leaves. Transcriptomics results showed that elevated CO2 decreased the expression of genes related to cell redox homeostasis, cadmium response, and lipid localization, but enhanced signal transduction, protein phosphorylation, NBS-LRR disease resistance proteins and subsequently programmed cell death in low-Mg shoots. By comparison, elevated CO2 enhanced the response of lipid localization (mainly LTP transfer protein/protease inhibitor), endomembrane system, heme binding and cell wall modification in high-Mg roots. Some of these transcriptomic results are substantially in accordance with our physiological and/or biochemical analysis. The present findings broaden our current understanding on the interactive effect of elevated CO2 and Mg levels in the Arabidopsis, which may help to design the novel metabolic engineering strategies to cope with Mg deficiency/excess in crops under elevated CO2. PMID:26881808

Mucuna pruriens Reduces Stress and Improves the Quality of Semen in Infertile Men

PubMed Central

Shukla, Kamla Kant; Ahmad, Mohammad Kaleem; Jaiswar, Shyam Pyari; Shankwar, Satya Narain; Tiwari, Sarvada Chandra

2010-01-01

The present investigation was undertaken to assess the role of Mucuna pruriens in infertile men who were under psychological stress. Study included 60 subjects who were undergoing infertility screening and were found to be suffering from psychological stress, assessed on the basis of a questionnaire and elevated serum cortisol levels. Age-matched 60 healthy men having normal semen parameters and who had previously initiated at least one pregnancy were included as controls. Infertile subjects were administered with M. pruriens seed powder (5 g day−1) orally. For carrying out morphological and biochemical analysis, semen samples were collected twice, first before starting treatment and second after 3 months of treatment. The results demonstrated decreased sperm count and motility in subjects who were under psychological stress. Moreover, serum cortisol and seminal plasma lipid peroxide levels were also found elevated along with decreased seminal plasma glutathione (GSH) and ascorbic acid contents and reduced superoxide dismutase (SOD) and catalase activity. Treatment with M. pruriens significantly ameliorated psychological stress and seminal plasma lipid peroxide levels along with improved sperm count and motility. Treatment also restored the levels of SOD, catalase, GSH and ascorbic acid in seminal plasma of infertile men. On the basis of results of the present study, it may be concluded that M. pruriens not only reactivates the anti-oxidant defense system of infertile men but it also helps in the management of stress and improves semen quality. PMID:18955292

Mucuna pruriens Reduces Stress and Improves the Quality of Semen in Infertile Men.

PubMed

Shukla, Kamla Kant; Mahdi, Abbas Ali; Ahmad, Mohammad Kaleem; Jaiswar, Shyam Pyari; Shankwar, Satya Narain; Tiwari, Sarvada Chandra

2010-03-01

The present investigation was undertaken to assess the role of Mucuna pruriens in infertile men who were under psychological stress. Study included 60 subjects who were undergoing infertility screening and were found to be suffering from psychological stress, assessed on the basis of a questionnaire and elevated serum cortisol levels. Age-matched 60 healthy men having normal semen parameters and who had previously initiated at least one pregnancy were included as controls. Infertile subjects were administered with M. pruriens seed powder (5 g day(-1)) orally. For carrying out morphological and biochemical analysis, semen samples were collected twice, first before starting treatment and second after 3 months of treatment. The results demonstrated decreased sperm count and motility in subjects who were under psychological stress. Moreover, serum cortisol and seminal plasma lipid peroxide levels were also found elevated along with decreased seminal plasma glutathione (GSH) and ascorbic acid contents and reduced superoxide dismutase (SOD) and catalase activity. Treatment with M. pruriens significantly ameliorated psychological stress and seminal plasma lipid peroxide levels along with improved sperm count and motility. Treatment also restored the levels of SOD, catalase, GSH and ascorbic acid in seminal plasma of infertile men. On the basis of results of the present study, it may be concluded that M. pruriens not only reactivates the anti-oxidant defense system of infertile men but it also helps in the management of stress and improves semen quality.

Antioxidant and antihyperlipidemic effect of Solanum nigrum fruit extract on the experimental model against chronic ethanol toxicity

PubMed Central

Arulmozhi, Vadivel; Krishnaveni, Mani; Karthishwaran, Kandhan; Dhamodharan, Ganesan; Mirunalini, Sankaran

2010-01-01

The possible protective effect of Solanum nigrum fruit extract (SNFEt) was investigated for its antioxidant and antihyperlipidemic activity against ethanol-induced toxicity in rats. The experimental animals were intoxicated with 20% ethanol (7.9 g/kg/day) for 30 days via gastric intubation. SNFEt was administered at the dose of 250 mg/kg body weight along with the daily dose of ethanol for 30 days. From the result it was observed that ethanol-induced rats showed a significant elevation in the levels of Thiobarbituric acid reactive substances (TBARS), which lowered the antioxidant defense systems, such as, reduced glutathione (GSH) and vitamins C and E, when compared to the controls. In the lipid profiles, the levels of total cholesterol (TC), triglycerides (TG), low density lipoproteins (LDL), very low density lipoproteins (VLDL), free fatty acids (FFA), and phospholipids were significantly elevated in the ethanol-induced group, whereas, the high density lipoproteins (HDL) were found to be reduced in the plasma, and the phospholipid levels were significantly decreased in the tissues. Supplementation of SNFEt improved the antioxidant status by decreasing the levels of TBARS and altering the lipid profiles to near normal. These activities were also compared to the standard drug silymarin (25 mg/kg body weight). Thus the findings of the present study indicated a significant antioxidant and antihyperlipidemic activity of Solanum nigrum fruits, which offered protection against ethanol-induced toxicity. PMID:20548935

Response to fasting in an unnaturally obese carnivore, the captive European polecat Mustela putorius.

PubMed

Mustonen, Anne-Mari; Puukka, Matti; Rouvinen-Watt, Kirsti; Aho, Jari; Asikainen, Juha; Nieminen, Petteri

2009-11-01

The European polecat (Mustela putorius) is a naturally lean carnivore prone to excessive weight gain in captivity. This study assessed its suitability to investigate the natural history of the obese phenotype displayed in overweight humans, domestic animals, and seasonally obese wild mammals. Ten farm-bred polecats were subjected to a 5-day fast with 10 controls. Obesity (40% body fat) was associated with an unfavorable plasma lipid profile and high glucose and insulin concentrations. The polecats were in phase II of fasting with normoglycemia, low liver carbohydrate stores, and decreased plasma concentrations of urea and most amino acids. Although the plasma nonesterified fatty acid (NEFA) levels were elevated, the adipose tissue lipase activities suggested a blunted lipolytic response. Lipid mobilization was more efficient from intraabdominal fat. The animals developed hepatic lipidosis with elevated NEFA influx into the liver and losses of n-3 polyunsaturated fatty acids and arginine as hypothetical etiological factors. The plasma leptin, insulin, and triiodothyronine levels decreased but were not accompanied by reduced sex steroid or increased stress hormone concentrations. The blunted lipolytic response often encountered in obesity suggests that the organism is trying to defend the obese phenotype. Liver lipidosis and decreased insulin and triiodothyronine levels seem to be among the most consistent responses to fasting manifested in diverse mammalian orders and different levels of body fatness. The polecat could be recommended as an easily accessible carnivorean model to study the natural history of the obese phenotype and its comorbidities.

Evaluation of lipid oxidative stress status and inflammation in atopic ocular surface disease

PubMed Central

Wakamatsu, Tais H.; Ayako, Igarashi; Takano, Yoji; Matsumoto, Yukihiro; Ibrahim, Osama M.A.; Okada, Naoko; Satake, Yoshiyuki; Fukagawa, Kazumi; Shimazaki, Jun; Tsubota, Kazuo; Fujishima, Hiroshi

2010-01-01

Background Although the oxidative stress status in atopic skin disease has been reported to be elevated, there are still no studies related to the status of oxidative stress in atopic ocular surface disease. The purpose of this study was to evaluate the ocular surface lipid oxidative stress status and inflammation in atopic keratoconjunctivitis (AKC) patients and normal subjects. Methods Twenty eight eyes of 14 patients (9 males, 5 females) with AKC and 18 eyes of 9 age and sex matched (4 males and 5 females) normal healthy controls were examined in this prospective study. The severity of atopic dermatitis (AD) was scored by the SCORing Atopic Dermatitis (SCORAD) index. All subjects underwent Schirmer test, tear film break up time (BUT), fluorescein/Rose Bengal stainings, tear collection, and brush cytology from the upper palpebral conjunctiva. The brush cytology samples were stained with Diff-Quik for differentiation of inflammatory cells and immunohistochemistry (IHC) staining with HEL (hexanoyl-lysine) and 4-HNE (4-hydroxy-2-nonenal) to study lipid oxidation. HEL and cytokine (interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ)) levels were measured by enzyme-linked immunosorbent assay (ELISA) from tear samples of AKC patients and control subjects. Toluidine Blue and IHC staining with HEL, 4-HNE and cluster of differentiation 45 (CD45) were performed on papillary samples of AKC patients. This study was conducted in compliance with the “Declaration of Helsinki.” Results The tear stability and vital staining scores were significantly worse in eyes of AKC patients (p<0.05) compared to the controls. Inflammatory cells and positively stained conjunctival epithelial cells for HEL and 4-HNE showed a significant elevation in brush cytology samples of AKC patients. Significantly higher levels of HEL and cytokines were detected in tears of AKC patients compared to controls. Papillary specimens also revealed many CD45 inflammatory cells as well as many cells positively stained with HEL and 4-HNE in IHC. A strong significant linear positive correlation between conjunctival inflammation and epithelial lipid oxidative stress status was observed. Conjunctival lipid oxidative stress also correlated strongly with tear HEL levels and epithelial damage scores. Conclusions The ocular surface disease in AKC was characterized by marked tear instability, ocular surface epithelial damage, increase in inflammatory infiltrates and presence of increased lipid oxidation. PMID:21139696

Effect of periocular humidity on the tear film lipid layer.

PubMed

Korb, D R; Greiner, J V; Glonek, T; Esbah, R; Finnemore, V M; Whalen, A C

1996-03-01

The purpose of this study was to determine the relationship between the tear film and humidity by examining whether alterations in periocular humidity influence the thickness of the tear film lipid layer. Thirteen dry eye subjects presenting with a baseline lipid layer thickness of < or = 60 nm were fitted with modified swim goggles in which the right eye (OD) was exposed to conditions of high humidity and the left eye (OS) remained exposed to ambient room conditions. The lipid layer was monitored over a 60-min time course with goggles on and for an additional 60 min following goggle removal. The OD lipid layer increased significantly in thickness within 5 min of exposure to conditions of high humidity (p < 0.0001), reaching a maximum increase of 66.4 nm after 15 min of goggle wear (p < 0.0001). This maximum increase to a lipid layer thickness of 120.5 nm was maintained at the 30- and 60-min goggle time points. No significant change was detected OS. Following goggle removal, OD values declined but remained significantly elevated over the OS lipid layer thickness throughout the 60-min postgoggle period. Moderate to total relief of dry eye symptoms was reported during goggle wear and generally persisted at a reduced level for 1-3 h following goggle removal. Increased periocular humidity results in an increase in tear film lipid layer thickness, possibly by providing an environment that is more conducive to the spreading of meibomian lipid and its incorporation into the tear film.

Salivary matrix metalloproteinase (MMP-8) levels and gelatinase (MMP-9) activities in patients with type 2 diabetes mellitus.

PubMed

Collin, H L; Sorsa, T; Meurman, J H; Niskanen, L; Salo, T; Rönkä, H; Konttinen, Y T; Koivisto, A M; Uusitupa, M

2000-10-01

We studied the salivary levels and activities of the matrix metalloproteinases (MMP) -8 and -9 in 45 type 2 diabetic patients and 77 control subjects. The patients' mean glycosylated haemoglobin (HbA1c) was 8.7%, indicating an unsatisfactory metabolic control of the disease. The MMP levels were further related to the clinical and microbiological periodontal findings as well as to salivary flow rate and other factors. The salivary flow rate, albumin and amylase concentrations were similar in type 2 diabetic patients to those in the control group. The mean gingival and periodontal pocket indexes were higher in the diabetes group. The number of potential periodontopathogenic bacteria was lower, however, in the diabetic than in the control group. Zymography and immunoblotting revealed that the major MMPs in the type 2 diabetic patients' saliva were MMP-8 and MMP-9. Salivary MMP levels and activities in type 2 diabetic patients were in general similar to those in the control group. However, the correlation coefficients using multiple regression analysis revealed that gingival bleeding, pocket depths and HbA1c were associated with increased MMP-8 levels which, in turn, were negatively predicted by elevated plasma lipid peroxide levels in the diabetic group. Our data on salivary MMP-8 and -9 do not support the concept of generalized neutrophil dysfunction in unbalanced diabetes. Moreover, plasma lipid peroxidation levels reflecting the increased oxidative burden, which is generated mainly by triggered neutrophils, do not indicate neutrophil dysfunction due to diabetes, but may rather be related to the increased tissue damage in an uncontrolled disease. However. advanced periodontitis in type 2 diabetes seems to be related to elevated salivary MMP-8 levels which might be useful in monitoring periodontal disease in diabetes.

Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study.

PubMed

Arend, A; Zilmer, M; Vihalemm, T; Selstam, G; Sepp, E

2000-01-01

As previously shown, dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) suppress connective tissue proliferation in the rat liver wound concurrent with an elevated level of lipid peroxidation. The present study was undertaken to investigate the influence of alpha-lipoic acid (LA), a natural anti-oxidant, on these effects of n-3 PUFAs. Rats were fed with a commercial pellet diet (control group) or with diets enriched with 10% of sunflower oil (n-6 group) or 10% of fish oil (n-3 group) for 8 weeks followed by addition of LA to the same diets for 10 days. Then a liver thermic wound was induced and the administration of LA was continued for 6 days. The proliferation of the connective tissue, the level of lipid peroxidation and their peroxidizability and the content of prostaglandins E2 and F2alpha were measured in the liver wounds. LA prevented the suppression of connective tissue proliferation in the healing wound induced by n-3 PUFAs, avoided the increase in peroxidation of lipids, reduced peroxidizability of lipids and modulated the decrease in PGE2 and PGF2alpha. The results indicate that dietary LA may prevent the suppression of liver wound healing induced by n-3 PUFAs.

Pharmacogenetics in the Development of Lipid Lowering Medications: Lomitapide & Mipomersen in Clinical Practice.

PubMed

Marbach, Jeffrey A; Thapa, Jhapat; Goldenberg, Edward; Duffy, Danielle

2015-08-01

The familial hypercholesterolemias (FH) are a group of undertreated genetically inherited disorders of lipid metabolism that lead to severely elevated cholesterol levels and early onset cardiovascular disease. Aggressive lifestyle modifications and lipid-lowering medications such as statins and bile acid sequestrants are the backbone of current treatment. Despite these interventions, homozygous FH (HoFH) patients are unable to reach LDL-C targets and remain at significantly increased risk of cardiovascular disease. Recently, two novel lipid-lowering medications, lomitapide and mipomersen, have been approved for the treatment of HoFH. We present two patients with HoFH who have been unable to reach target LDL-C goals on standard therapy. Patient A is a 41-year-old male and patient B is a 64-year-old female, both of whom have complex histories of multi-vessel coronary artery disease. In attempt to improve their LDL-C levels and lower their cardiovascular risk, lomitapide and mipomersen were initiated in patient A and B, respectively. Through inhibition of the microsomal triglyceride transfer protein, lomitapide prevents the formation of triglyceride rich lipoproteins. Mipomersen is an antisense oligonucleotide that inhibits the translation of apolipoprotein B-100. Both medications employ novel mechanisms developed through advances in pharmacogenetic technology and achieve unprecedented LDL-C reductions.

Effect of high fluoride and high fat on serum lipid levels and oxidative stress in rabbits.

PubMed

Sun, Liyan; Gao, Yanhui; Zhang, Wei; Liu, Hui; Sun, Dianjun

2014-11-01

The purpose of this study was to explore the effects of high fluoride and high fat on triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total antioxidant capacity (T-AOC), lipid peroxide (LPO) and malondialdehyde (MDA) in rabbits. A factorial experimental design was used, with two factors (fluoride and fat) and three levels. Seventy-two male rabbits were randomly assigned into nine groups according to initial weight and serum lipid levels. The rabbits were fed with basic feed, moderate fat feed or high fat feed and drank tap water, fluoridated water at levels of 50 and 100mgfluorion/L freely. Biological materials were collected after 5 months, and serum lipid, T-AOC, LPO, and MDA levels were then measured. Using these data, the separate and interactive effects of high fluoride and high fat were analyzed. High fluoride and high fat both increased serum levels of TC, HDL-C and LDL-C significantly (P<0.05), and there was also a synergistic effect between high fluoride and high fat (P<0.05). High fluoride and high fat had different effects on TG levels: high fat significantly increased TG levels (P<0.01) whereas high fluoride had nothing to do with TG levels (P>0.05). High fat significantly elevated LPO and MDA levels and lowered T-AOC levels in serum (P<0.05). Similarly, high fluoride significantly increased LPO and MDA levels in serum (P<0.05). However, there was no interactive effect between high fat and high fluoride on these indexes. In summary, high fluoride and high fat increased serum TC and LDL-C levels individually and synergistically, and this would cause and aggravate hypercholesterolemia in rabbits. At the same time, high fluoride and high fat both made the accumulation of product of oxidative stress in experimental animals. Copyright © 2014 Elsevier B.V. All rights reserved.

Up-regulation of fatty acid synthase induced by EGFR/ERK activation promotes tumor growth in pancreatic cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bian, Yong, E-mail: drbiany@126.com; Yu, Yun; Wang, Shanshan

2015-08-07

Lipid metabolism is dysregulated in many human diseases including atherosclerosis, type 2 diabetes and cancers. Fatty acid synthase (FASN), a key lipogenic enzyme involved in de novo lipid biosynthesis, is significantly upregulated in multiple types of human cancers and associates with tumor progression. However, limited data is available to understand underlying biological functions and clinical significance of overexpressed FASN in pancreatic ductal adenocarcinoma (PDAC). Here, upregulated FASN was more frequently observed in PDAC tissues compared with normal pancreas in a tissue microarray. Kaplan–Meier survival analysis revealed that high expression level of FASN resulted in a significantly poor prognosis of PDACmore » patients. Knockdown or inhibition of endogenous FASN decreased cell proliferation and increased cell apoptosis in HPAC and AsPC-1 cells. Furthermore, we demonstrated that EGFR/ERK signaling accounts for elevated FASN expression in PDAC as ascertained by performing siRNA assays and using specific pharmacological inhibitors. Collectively, our results indicate that FASN exhibits important roles in tumor growth and EGFR/ERK pathway is responsible for upregulated expression of FASN in PDAC. - Highlights: • Increased expression of FASN indicates a poor prognosis in PDAC. • Elevated FASN favors tumor growth in PDAC in vitro. • Activation of EGFR signaling contributes to elevated FASN expression.« less

Cadmium Exposure is Associated with the Prevalence of Dyslipidemia.

PubMed

Zhou, Zhou; Lu, Yong-Hui; Pi, Hui-Feng; Gao, Peng; Li, Min; Zhang, Lei; Pei, Li-Ping; Mei, Xiang; Liu, Lin; Zhao, Qi; Qin, Qi-Zhong; Chen, Yu; Jiang, Yue-Ming; Zhang, Zhao-Hui; Yu, Zheng-Ping

2016-01-01

Cadmium is a widespread environmental and occupational pollutant that accumulates in human body with a biological half-life exceeding 10 years. Cadmium exposure has been demonstrated to increase rates of cardiovascular diseases. Whether occupational cadmium exposure is associated with the increase in the prevalence of dyslipidemia and hence contributes to the risk of cardiovascular diseases is still equivocal. To test the hypothesis that exposure to cadmium is related to the prevalence of dyslipidemia, we examined the associations between blood cadmium concentration and the prevalence of dyslipidemia in workers occupationally exposed to cadmium in China. A cross-sectional survey on demographic data, blood cadmium level and lipid profile in cadmium exposed workers from seven cadmium smelting factories in central and southwestern China was conducted. We measured blood cadmium concentration and lipid components of 1489 cadmium exposed workers. The prevalence of dyslipidemia was compared across blood cadmium quartiles. Associations between the blood cadmium concentrations and the prevalence of dyslipidemia were assessed using confounder adjusted linear and logistic regressions. The blood cadmium concentration was 3.61±0.84µg/L ( mean ±SD). The prevalence of dyslipidemia in this occupational population was 66.3%. Mean blood cadmium concentration of workers with dyslipedemia was significantly higher than that of workers without dyslipidemia (p <0.01). The prevalence of dyslipidemia increased dose-dependently with elevations in blood cadmium concentrations (p for trend <0.001). Elevated levels of blood cadmium were associated with BMI, education attainment, income, smoking status and duration of exposure (all p <0.01). Furthermore, the profile of blood lipid was obviously changed in this occupational population. The prevalence of high TC, high TG, Low HDL-C and high LDL-C rose with increases in blood cadmium levels dose-dependently (p for trend <0.001). The odds ratios (95% confidence interval) for dyslipidemia across the increasing blood cadmium quartiles were 1.21(1.16-1.55), 1.56(1.11-1.87), 1.79(1.26-2.25) respectively (referencing to 1.00; p for trend <0.001), after multivariate adjustment for BMI, education attainment, income, lifestyle factors and duration of exposure, the association between blood cadmium concentrations and the prevalence of dyslipidemia remained unchanged (all p for trend <0.001). Elevated blood cadmium concentration is associated with prevalence of dyslipidemia. Cadmium exposure could alter lipid metabolism in humans. It is imperative to control cadmium exposure of occupational population in cadmium related industries and reduce adverse health effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

Relationship of the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio to the remainder of the lipid profile: The Very Large Database of Lipids-4 (VLDL-4) study.

PubMed

Quispe, Renato; Manalac, Raoul J; Faridi, Kamil F; Blaha, Michael J; Toth, Peter P; Kulkarni, Krishnaji R; Nasir, Khurram; Virani, Salim S; Banach, Maciej; Blumenthal, Roger S; Martin, Seth S; Jones, Steven R

2015-09-01

High levels of the triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio are associated with obesity, metabolic syndrome, and insulin resistance. We evaluated variability in the remaining lipid profile, especially remnant lipoprotein particle cholesterol (RLP-C) and its components (very low-density lipoprotein cholesterol subfraction 3 and intermediate-density lipoprotein cholesterol), with variability in the TG/HDL-C ratio in a very large study cohort representative of the general U.S. We examined data from 1,350,908 US individuals who were clinically referred for lipoprotein cholesterol ultracentrifugation (Atherotech, Birmingham, AL) from 2009 to 2011. Demographic information other than age and sex was not available. Changes to the remaining lipid profile across percentiles of the TG/HDL-C ratio were quantified, as well as by three TG/HDL-C cut-off points previously proposed in the literature: 2.5 (male) and 2 (female), 3.75 (male) and 3 (female), and 3.5 (male and female). The mean age of our study population was 58.7 years, and 48% were men. The median TG/HDL-C ratio was 2.2. Across increasing TG/HDL-C ratios, we found steadily increasing levels of RLP-C, non-HDL-C and LDL density. Among the lipid parameters studied, RLP-C and LDL density had the highest relative increase when comparing individuals with elevated TG/HDL-C levels to those with lower TG/HDL-C levels using established cut-off points. Approximately 47% of TG/HDL-C ratio variance was attributable to RLP-C. In the present analysis, a higher TG/HDL-C ratio was associated with an increasingly atherogenic lipid phenotype, characterized by higher RLP-C along with higher non-HDL-C and LDL density. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of zinc and multimineral vitamin supplementation on glycemic and lipid control in adult diabetes.

PubMed

Gunasekara, Priyanka; Hettiarachchi, Manjula; Liyanage, Chandrani; Lekamwasam, Sarath

2011-01-26

To evaluate the effects of zinc with or without other antioxidants on blood glucose, lipid profile, and serum creatinine in adult diabetics on long-term follow-up. Patients (n = 96) were randomly allocated to three groups: group A (n = 29) was supplemented with oral zinc sulfate (22 mg/day) and multivitamin/mineral (zinc+MVM) preparation; group B (n = 31) was given the same preparation without zinc (MVM); and group C (n = 36) was given a matching placebo for a period of 4 months in a single-blinded study. Blood samples were taken at baseline and after 4 months of supplementation to assess blood glucose (fasting and postprandial) and glycosylated hemoglobin (Hb(A1C)%) and serum levels of zinc, creatinine, and lipids. The zinc+MVM group had a mean change of fasting blood sugar -0.33 mmol/L (standard error of the mean 0.21 mmol/L) and was significant (P = 0.05) when compared with the other two groups (mean change in the MVM group +0.19 (0.31) mmol/L and +0.43 (0.23) mmol/L in the control group, respectively). The Hb(A1C)% level reduced significantly, irrespective of the baseline level, in zinc+MVM-supplemented individuals. In the other two groups, the change of Hb(A1C)% level was not significant. Serum lipid levels reduced significantly in the zinc+MVM and MVM groups. Zinc+MVM supplementation showed beneficial effects in the metabolic control of adult diabetics in addition to elevating their serum zinc level. Zinc supplementation improved glycemic control measured by Hb(A1C)% and fasting and postprandial glucose. Furthermore, zinc supplementation lowered serum cholesterol and cholesterol/high-density lipoprotein ratio.

Mass spectrometry profiling of oxylipins, endocannabinoids, and N-acylethanolamines in human lung lavage fluids reveals responsiveness of prostaglandin E2 and associated lipid metabolites to biodiesel exhaust exposure.

PubMed

Gouveia-Figueira, Sandra; Karimpour, Masoumeh; Bosson, Jenny A; Blomberg, Anders; Unosson, Jon; Pourazar, Jamshid; Sandström, Thomas; Behndig, Annelie F; Nording, Malin L

2017-04-01

The adverse effects of petrodiesel exhaust exposure on the cardiovascular and respiratory systems are well recognized. While biofuels such as rapeseed methyl ester (RME) biodiesel may have ecological advantages, the exhaust generated may cause adverse health effects. In the current study, we investigated the responses of bioactive lipid mediators in human airways after biodiesel exhaust exposure using lipidomic profiling methods. Lipid mediator levels in lung lavage were assessed following 1-h biodiesel exhaust (average particulate matter concentration, 159 μg/m 3 ) or filtered air exposure in 15 healthy individuals in a double-blinded, randomized, controlled, crossover study design. Bronchoscopy was performed 6 h post exposure and lung lavage fluids, i.e., bronchial wash (BW) and bronchoalveolar lavage (BAL), were sequentially collected. Mass spectrometry methods were used to detect a wide array of oxylipins (including eicosanoids), endocannabinoids, N-acylethanolamines, and related lipid metabolites in the collected BW and BAL samples. Six lipids in the human lung lavage samples were altered following biodiesel exhaust exposure, three from BAL samples and three from BW samples. Of these, elevated levels of PGE 2 , 12,13-DiHOME, and 13-HODE, all of which were found in BAL samples, reached Bonferroni-corrected significance. This is the first study in humans reporting responses of bioactive lipids following biodiesel exhaust exposure and the most pronounced responses were seen in the more peripheral and alveolar lung compartments, reflected by BAL collection. Since the responsiveness and diagnostic value of a subset of the studied lipid metabolites were established in lavage fluids, we conclude that our mass spectrometry profiling method is useful to assess effects of human exposure to vehicle exhaust.

Reasons for the upsetting cholesterol level during the community investigation from residents, physicians, and social aspects: the China Cholesterol Education Program (CCEP).

PubMed

Xie, Jiang; Guan, Fei; Wang, Jia-Hong; Hu, Da-Yi

2011-10-01

The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects. Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire, some of which were about basic knowledge of lipids. About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P < 0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P < 0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P < 0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels. Management of hypercholesterolemia should be an important component of health strategy in Beijing. Education is imperative for residents as well as for physicians.

Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination

PubMed Central

Furman, David; Hejblum, Boris P.; Simon, Noah; Jojic, Vladimir; Dekker, Cornelia L.; Thiébaut, Rodolphe; Tibshirani, Robert J.; Davis, Mark M.

2014-01-01

Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females. PMID:24367114

Mipomersen sodium: a new option for the treatment of familial hypercholesterolemia.

PubMed

Haddley, K

2011-12-01

In collaboration with Genzyme, Isis Pharmaceuticals has developed mipomersen sodium (ISIS-310312), a synthetic second-generation 20-base phosphorothioate antisense oligonucleotide (ASO) that targets messenger RNA encoding apolipoprotein B-100 (Apo B-100). Elevated cholesterol levels, in particular low-density lipoprotein cholesterol (LDL-C) which contains a single apolipoprotein B (ApoB) molecule, have been directly correlated with the incidence of cardiovascular events. Preclinical investigations in transgenic mice have demonstrated that lowering LDL-C or ApoB can reduce aortic plaque formation associated with atherosclerosis. Mipomersen pharmacokinetics showed a wide and rapid tissue distribution and a slow prolonged elimination phase of several days in a range of species. Mipomersen displayed dose-dependent efficacy in lowering LDL-C, ApoB, triglycerides, total cholesterol and other low-density lipoproteins in healthy volunteers with mild hyperlipidemia. Similar decreases were observed in patients on stable lipid-lowering therapy for familial hypercholesterolemia with baseline LDL-C levels declining towards clinically desirable concentrations of 70 mg/dL. The efficacy of mipomersen in treating patients with severe heterozygous or homozygous familial hypercholesterolemia with cardiovascular complications has been recently assessed. There have been no serious adverse events noted with treatment and mipomersen can be administered in combination with other lipid-lowering therapies. One concern noted was an elevation in liver transaminase concentrations, although these increases were reversible.

Hypoglycemic and hypolipidemic effects of Aronia melanocarpa fruit juice in streptozotocin-induced diabetic rats.

PubMed

Valcheva-Kuzmanova, S; Kuzmanov, K; Tancheva, S; Belcheva, A

2007-03-01

Aronia melanocarpa fruit juice (AMFJ) is rich in phenolic antioxidants, especially flavonoids from the anthocyanin subclass. The aim of the present study was to investigate the influence of AMFJ on plasma glucose and lipids in diabetic rats. Diabetes was induced by an intraperitoneal injection of streptozotocin (50 mg/kg). AMFJ was applied by gavage at doses of 10 and 20 ml/kg for 6 weeks to normal and diabetic rats. Streptozotocin caused a significant elevation of plasma glucose by 141% and of plasma triglycerides (TG) by 64% in comparison with normal control rats and induced statistically insignificant elevations of total cholesterol and LDL-cholesterol and a reduction of HDL-cholesterol. Applied to normal rats, AMFJ did not influence plasma glucose and lipid levels. Applied to diabetic rats, AMFJ (10 and 20 ml/kg) significantly reduced plasma glucose by 44% and 42% and TG by 35% and 39%, respectively, to levels that did not significantly differ from those of the normal control rats and counteracted the influence of streptozotocin on total cholesterol, LDL-cholesterol and HDL-cholesterol. In conclusion, AMFJ significantly decreased the streptozotocin-induced abnormalities in blood glucose and TG in diabetic rats and might be useful in prevention and control of diabetes mellitus and diabetes-associated complications. Copyright 2007 Prous Science.

Sida rhomboidea.Roxb extract alleviates pathophysiological changes in experimental in vivo and in vitro models of high fat diet/fatty acid induced non-alcoholic steatohepatitis.

PubMed

Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Dandekar, Deven S; Devkar, Ranjitsinh V; Ramachandran, A V

2012-03-01

The present study was aim to evaluate protective role of Sida rhomboidea.Roxb (SR) extract against high fat diet/fatty acid induced pathophysiological alterations in experimental model of non-alcoholic steatohepatitis (NASH). Effect of SR extract on plasma levels of markers of hepatic damage, plasma and hepatic lipids, mitochondrial oxidative stress, status of enzymatic and non-enzymatic antioxidants and histopathological changes in liver tissue were evaluated in high fat diet fed C57BL/6J mice. Also, the effect of SR supplementation on lipid accumulation, lipid peroxidation, cytotoxicity and cell viability were evaluated in oleic acid treated HepG2 cells. Supplementation of NASH mice with SR extract prevented high fat diet induced elevation in plasma marker enzymes of liver damage, plasma and hepatic lipids, mitochondrial oxidative stress and compromised enzymatic and non-enzymatic antioxidant status. Further, addition of SR extract to in vitro HepG2 cells minimized oleic acid induced lipid accumulation, higher lipid peroxidation, cytotoxicity and reduced cell viability. These in vivo and in vitro studies suggest that SR extract has the potential of preventing high fat/fatty acid induced NASH mainly due to its hypolipidemic and antioxidant activities. Copyright © 2010 Elsevier GmbH. All rights reserved.

Diacylglycerol kinase-δ regulates AMPK signaling, lipid metabolism, and skeletal muscle energetics.

PubMed

Jiang, Lake Q; de Castro Barbosa, Thais; Massart, Julie; Deshmukh, Atul S; Löfgren, Lars; Duque-Guimaraes, Daniella E; Ozilgen, Arda; Osler, Megan E; Chibalin, Alexander V; Zierath, Juleen R

2016-01-01

Decrease of AMPK-related signal transduction and insufficient lipid oxidation contributes to the pathogenesis of obesity and type 2 diabetes. Previously, we identified that diacylglycerol kinase-δ (DGKδ), an enzyme involved in triglyceride biosynthesis, is reduced in skeletal muscle from type 2 diabetic patients. Here, we tested the hypothesis that DGKδ plays a role in maintaining appropriate AMPK action in skeletal muscle and energetic aspects of contraction. Voluntary running activity was reduced in DGKδ(+/-) mice, but glycogen content and mitochondrial markers were unaltered, suggesting that DGKδ deficiency affects skeletal muscle energetics but not mitochondrial protein abundance. We next determined the role of DGKδ in AMPK-related signal transduction and lipid metabolism in isolated skeletal muscle. AMPK activation and signaling were reduced in DGKδ(+/-) mice, concomitant with impaired lipid oxidation and elevated incorporation of free fatty acids into triglycerides. Strikingly, DGKδ deficiency impaired work performance, as evident by altered force production and relaxation dynamics in response to repeated contractions. In conclusion, DGKδ deficiency impairs AMPK signaling and lipid metabolism, thereby highlighting the deleterious role of excessive lipid metabolites in the development of peripheral insulin resistance and type 2 diabetes pathogenesis. DGKδ deficiency also influences skeletal muscle energetics, which may lead to low physical activity levels in type 2 diabetes. Copyright © 2016 the American Physiological Society.

Effect of estradiol and hydrocortisone on the process of peroxidation of mitochondrial membrane lipids in irradiated rat liver. [/sup 60/Co. gamma. rays

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saksonov, N.P.

Experiments were conducted on male, mongrel albino rats. They were exposed to /sup 60/Co ..gamma.. radiation once, in a dosage of 600 R. Estradiol and hydrocortisone were given intraperitoneally at the rate of 1 mg/kg, 2 h before irradiation or 2, 24 and 72 h after exposure. The animals were sacrificed 5 days after irradiation. These studies established that single exposure of animals to radiation in a dosage of 600 R leads to activation of processes of peroxidation of membrane lipids of the hepatic mitochondria. When estradiol is given 2 and 4 days before sacrificing, one observes acceleration of processesmore » of peroxidation of lipids without reliable change in malonic dialdehyde content. Administration of estrogen 5 days prior to sacrificing leads to a drop of malonic dialdehyde level, which is indicative of attenuation of the process of lipid peroxidation. Administration of hydrocortisone is associated with elevation of the latency period and level of peroxidation after 5 days, as compared to intact animals. Injection of this hormone 2 days before sacrificing the animals leads to attenuation and decrease in rate of peroxidation. The obtained data indicate that there are different mechanisms involved in the inhibitory effects of estradiol and hydrocortisone on peroxidation of lipids of mitochondrial membranes of the rat liver, activated by irradiation. Thus, it may be assumed that steroid hormones are actively involved in regulation of lipid peroxidation when mammals are exposed to radiation. (ERB)« less

Do treatment quality indicators predict cardiovascular outcomes in patients with diabetes?

PubMed

Sidorenkov, Grigory; Voorham, Jaco; de Zeeuw, Dick; Haaijer-Ruskamp, Flora M; Denig, Petra

2013-01-01

Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes. A cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT) database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR) with 95% confidence intervals. Lipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR = 0.77, 0.67-0.88; HR = 0.75, 0.59-0.94). Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR = 0.72, 0.56-0.93). Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR = 0.73, 0.60-0.89). Treatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient outcomes. These results question whether all treatment indicators are valid measures to judge quality of health care and its economics.

Early and late HIV-1 membrane fusion events are impaired by sphinganine lipidated peptides that target the fusion site.

PubMed

Klug, Yoel A; Ashkenazi, Avraham; Viard, Mathias; Porat, Ziv; Blumenthal, Robert; Shai, Yechiel

2014-07-15

Lipid-conjugated peptides have advanced the understanding of membrane protein functions and the roles of lipids in the membrane milieu. These lipopeptides modulate various biological systems such as viral fusion. A single function has been suggested for the lipid, binding to the membrane and thus elevating the local concentration of the peptide at the target site. In the present paper, we challenged this argument by exploring in-depth the antiviral mechanism of lipopeptides, which comprise sphinganine, the lipid backbone of DHSM (dihydrosphingomyelin), and an HIV-1 envelope-derived peptide. Surprisingly, we discovered a partnership between the lipid and the peptide that impaired early membrane fusion events by reducing CD4 receptor lateral diffusion and HIV-1 fusion peptide-mediated lipid mixing. Moreover, only the joint function of sphinganine and its conjugate peptide disrupted HIV-1 fusion protein assembly and folding at the later fusion steps. Via imaging techniques we revealed for the first time the direct localization of these lipopeptides to the virus-cell and cell-cell contact sites. Overall, the findings of the present study may suggest lipid-protein interactions in various biological systems and may help uncover a role for elevated DHSM in HIV-1 and its target cell membranes.

Ultraperformance convergence chromatography-high resolution tandem mass spectrometry for lipid biomarker profiling and identification.

PubMed

Jones, Jace W; Carter, Claire L; Li, Fei; Yu, Jianshi; Pierzchalski, Keely; Jackson, Isabel L; Vujaskovic, Zeljko; Kane, Maureen A

2017-03-01

Lipids represent biologically ubiquitous and highly dynamic molecules in terms of abundance and structural diversity. Whereas the potential for lipids to inform on disease/injury is promising, their unique characteristics make detection and identification of lipids from biological samples analytically demanding. We report the use of ultraperformance convergence chromatography (UPC 2 ), a variant of supercritical fluid chromatography, coupled to high-resolution, data-independent tandem mass spectrometry for characterization of total lipid extracts from mouse lung tissue. The UPC 2 platform resulted in lipid class separation and when combined with orthogonal column chemistries yielded chromatographic separation of intra-class species based on acyl chain hydrophobicity. Moreover, the combined approach of using UPC 2 with orthogonal column chemistries, accurate mass measurements, time-aligned low- and high-collision energy total ion chromatograms, and positive and negative ion mode product ion spectra correlation allowed for confident lipid identification. Of great interest was the identification of differentially expressed ceramides that were elevated 24 h post whole thorax lung irradiation. The identification of lipids that were elevated 24 h post-irradiation signifies a unique opportunity to investigate early mechanisms of action prior to the onset of clinical symptoms in the whole thorax lung irradiation mouse model. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of gamma-Radiation on Select Lipids and Antioxidants

NASA Technical Reports Server (NTRS)

Gandolph, Jacob; Mauer, Lisa; Perchonok, Michele

2006-01-01

Radiation encountered on an extended duration space mission (estimates of 3 Sieverts for a mission to Mars) poses a threat not only to human health, but also to the quality, nutritional value, and palatability of the food system. Free radicals generated by radiation interaction with foods may initiate many unwanted reactions including: 1) autoxidation in lipids that alters flavor, odor, and concentrations of essential fatty acids, and 2) depletion of antioxidants food products and dietary supplements. Studies have shown that antioxidants may provide long term health protection from oxidative stress caused by radiation exposure; therefore, consumption of antioxidants will be important. Stability of essential fatty acids is also important for astronauts long-term health status. The objectives of this study were to characterize the effects of low dose gamma-radiation on lipids and antioxidants by monitoring oxidation and reducing power, respectively, in model systems. Select oils and antioxidants were exposed to levels of gamma-radiation ranging from 0 to 1000 Gy (1 Gy = 1 Sv) using a Gammacell 220 and stored at ambient or elevated temperatures (65 C) for up to 3 months prior to analysis. A Fricke dosimeter was used to verify differences between the radiation doses administered. Primary and secondary products of lipid oxidation in soybean and peanut oils were monitored using conjugated diene and 2-thiobarbituric acid (TBARs) assays. Changes in fatty acid composition and formation and vitamin E levels were also measured. The reducing power of antioxidant compounds, including vitamins C and E and beta-carotene, was determined using the ferric reducing antioxidant power (FRAP) assay. Significant differences (alpha =0.05) were present between all radiation doses tested using the Fricke dosimeter. Increasing radiation doses above 3 Sv resulted in significantly (alpha =0.05) elevated levels of oxidation and free fatty acids in soybean and peanut oils. Decreases in concentrations of essential fatty acids upon increasing radiation doses were also observed. Increasing radiation doses caused significant (alpha =0.05) decreases in reducing power and hence the effectiveness of vitamins C and E as well as beta-carotene. This work establishes a need for quantifying the effects of space relevant radiation doses in the development of a food system for an extended duration mission and for identifying threshold radiation levels that will impact the useful shelf-life of the variety of foods that will be sent. Eventual rancidity of lipids and the loss of antioxidant bioprotective effects are major concerns for the acceptability and nutritional profile of a food system.

Effects of oral contraceptives on metabolic profile in women with polycystic ovary syndrome: A meta-analysis comparing products containing cyproterone acetate with third generation progestins.

PubMed

Amiri, Mina; Ramezani Tehrani, Fahimeh; Nahidi, Fatemeh; Kabir, Ali; Azizi, Fereidoun; Carmina, Enrico

2017-08-01

Although oral contraceptives (OCs) are the most common treatment in women with polycystic ovary syndrome (PCOS), their effects and safety on the metabolic profiles of these patients are relatively unknown. In this meta-analysis the effects of the different durations (from 3months to 1year) of OC treatment using cyproterone acetate (CA) or third generation progestins on metabolic profile of patients with PCOS were assessed. PubMed, Scopus, Google Scholar and ScienceDirect databases (2001-2015) were searched to identify clinical trials investigating the effects of OC containing CA or third generation progestins on metabolic profiles of women with PCOS. Both fixed and random effect models were used. Subgroup analyses were performed based on the progestin compounds used and on duration of treatment. Oral contraceptive (OC) use was found to be associated with a worsening in lipid profiles but no changes were observed in other metabolic outcomes, including body mass index (BMI), fasting blood glucose (FBG), fasting insulin, homeostatic model for measuring insulin resistance (HOMA-IR) and in blood pressure (BP) values. All studied OCs showed similar effects on lipid profiles but with different timings, with products containing CA, requiring 6months to raise high density lipoprotein-cholesterol (HDL-C) levels and 12months to increase triglycerides (TG). On the contrary, products containing drospirenone (DRSP) or desogestrel (DSG) increased HDL-C after only 3months but determined elevations of TG after 6months. All OCs induced an increase in low density lipoprotein-cholesterol (LDL-C) after 12months of use. The study shows that, in women with PCOS, OC use is associated with significant changes in lipid profiles, including elevation not only in HDL-C but also in TG and LDL-C. All OCs studied showed similar effects but with different timings, with products containing CA generally requiring more prolonged use to increase serum lipids. Instead, OC use does not affect body weight, BP or glucose levels, with only some minor increase of fasting insulin levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Elevated lipoprotein(a) levels are associated with coronary artery calcium scores in asymptomatic individuals with a family history of premature atherosclerotic cardiovascular disease.

PubMed

Verweij, Simone L; de Ronde, Maurice W J; Verbeek, Rutger; Boekholdt, S Matthijs; Planken, R Nils; Stroes, Erik S G; Pinto-Sietsma, Sara-Joan

2018-02-16

Elevated lipoprotein(a) (Lp(a)) levels are associated with increased risk for atherosclerotic cardiovascular disease (ASCVD). Individuals with a family history of premature ASCVD are at increased cardiovascular risk with concomitantly a higher burden of (subclinical) atherosclerosis. However, whether Lp(a) contributes to the increased atherosclerotic burden in these individuals remains to be established. In this study, we evaluated the association between Lp(a) levels and coronary atherosclerotic burden, assessed by coronary arterty calcium (CAC) scores, in asymptomatic individuals with a family history of premature ASCVD. Lp(a) levels and other ASCVD risk factors were assessed in 432 individuals with premature ASCVD and in 937 healthy asymptomatic family members. CAC scores were only measured in asymptomatic family members. In this cohort, 16% had elevated Lp(a) levels, defined as ≥ 50 mg/dL. Among healthy family members, elevated Lp(a) levels were associated with both absolute CAC scores of ≥ 100 (odds ratio [OR] 1.79 [95% confidence interval {CI} 1.13-2.83]) as well as with age- and gender-corrected CAC scores ≥ 80th percentile (OR 1.69 [95% CI 1.14-2.50]). This coincides with a higher prevalence of cardiovascular events (OR 1.48 [95% CI 1.11-2.01]) in the whole cohort. Elevated Lp(a) levels were associated with higher CAC scores, both absolute as well as age- and gender-corrected percentiles, in individuals with a family history of premature ASCVD. These data imply that Lp(a) accelerates progression of atherosclerosis in these individuals, thereby contributing to their increased ASCVD risk. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study.

PubMed

Kim, Sang-Wook; Ha, Ki-Chan; Choi, Eun-Kyung; Jung, Su-Young; Kim, Min-Gul; Kwon, Dae-Young; Yang, Hye-Jung; Kim, Min-Jung; Kang, Hee-Joo; Back, Hyang-Im; Kim, Sun-Young; Park, Soo-Hyun; Baek, Hum-Young; Kim, Yong-Jae; Lee, Joon-Yeol; Chae, Soo-Wan

2013-03-08

Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. ClinicalTrials.gov: NCT01634256

The effectiveness of fermented turmeric powder in subjects with elevated alanine transaminase levels: a randomised controlled study

PubMed Central

2013-01-01

Background Previous animal studies have shown that Curcuma longa (turmeric) improves liver function. Turmeric may thus be a promising ingredient in functional foods aimed at improving liver function. The purpose of the study is to investigate the hepatoprotective effect of fermented turmeric powder (FTP) on liver function in subjects with elevated alanine transaminase (ALT) levels. Methods A randomised, double-blind, placebo-controlled trial was conducted between November 2010 and April 2012 at the clinical trial center for functional foods of the Chonbuk National University Hospital. The trial included 60 subjects, 20 years old and above, who were diagnosed mild to moderate elevated ALT levels between 40 IU/L and 200 IU/L. Sixty subjects were randomised to receive FTP 3.0 g per day or placebo 3.0 g per day for 12 weeks. The treatment group received two capsules of FTP three times a day after meals, for 12 weeks. The primary efficacy endpoint was change in the ALT levels in the two groups. The secondary efficacy endpoints included its effect on aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TB), and lipid profiles. Safety was assessed throughout the study using ongoing laboratory tests. Adverse events (AEs) were also recorded. Results Sixty subjects were randomised in the study (30 into the FTP group, 30 into the placebo group), and among them, twelve subjects were excluded from the analysis for protocol violation, adverse events or consent withdrawal. The two groups did not differ in baseline characteristics. After 12 weeks of treatment, 48 subjects were evaluated. Of the 48 subjects, 26 randomly received FTP capsules and 22 received placebo. The FTP group showed a significant reduction in ALT levels after 12 weeks of treatment compared with the placebo group (p = 0.019). There was also observed that the serum AST levels were significantly reduce in the FTP group than placebo group (p = 0.02). The GGT levels showed a tendency to decrease, while the serum alkaline phosphatase (ALP), TB, and lipids levels were not modified. There were no reported severe AEs during this study, or abnormalities observed on blood glucose, total protein, albumin, blood urea nitrogen (BUN), and creatinine levels. Conclusion The data of this trial indicate that FTP is effective and safe, generally well-tolerated without severe AEs, in the treatment of subjects with elevated ALT levels over a 12 weeks period. Trial registration ClinicalTrials.gov: http://NCT01634256 PMID:23497020

Bigger is not always better for overwintering young-of-year steelhead

USGS Publications Warehouse

Connolly, P.J.; Petersen, J.H.

2003-01-01

Many fishes occur across broad ranges of latitude and elevation, where winter temperatures can vary from mild to harsh. We conducted a laboratory experiment with three sizes of age-0 steelhead Oncorhynchus mykiss to examine growth, condition, and energy reserves under low rations at three levels of water temperature typical of this species' distribution during winter. At the end of the 111-d experiment, all three starting sizes of age-0 steelhead (small, 2-3 g; medium, 3-4 g; large, 4-5 g) held in 3??C water had lower total lipid weight than those held in 6??C and 9??C water. Large fish had higher total lipid weight than small fish at the onset of the experiment and retained higher amounts at the end. However, large fish had either the lowest percentage increases or the highest percentage decreases in fork length, biomass, condition factor, total lipid weight, and percent lipids within all thermal treatments. The magnitude of the differences between small and large fish was highest in the warmest (9??C) water. We used bioenergetics simulations of juvenile steelhead growth to examine fish response to initial size, winter temperature, and food availability. Relatively warm water temperatures in winter, coupled with limited food availability, may present more of a physiological challenge to larger age-0 steelhead than to smaller fish. Our results suggest that achievement of large size before the start of a steelhead's first winter can have a cost under episodic conditions found across the wide ranges of latitude and elevation within this species' distribution.

Gastroprotective effect of cyanidin 3-glucoside on ethanol-induced gastric lesions in rats.

PubMed

Li, Chun-Ying; Xu, Hong-De; Zhao, Bing-Tian; Chang, Hyo-Ihl; Rhee, Hae-Ik

2008-12-01

This study investigated the in vivo protective effect of cyanidin 3-glucoside (C3G) against ethanol-induced gastric lesions in rats. The experimental rats were treated with 80% ethanol after pretreatment with various doses of C3G (4 and 8 mg/kg of body weight), and the control rats received only 80% ethanol. Oral pretreatment with C3G significantly inhibited the formation of ethanol-induced gastric lesions and the elevation of the lipid peroxide level. In addition, pretreatment with C3G significantly increased the level of glutathione and the activities of radical scavenging enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase, in gastric tissues. These results suggest that the gastroprotective effect of C3G removes the ethanol-induced lipid peroxides and free radicals and that it may offer a potential remedy for the treatment of gastric lesions.

Acceleration of lipid peroxidation in alpha-tocopherol transfer protein-knockout mice following the consumption of drinking water containing a radical initiator.

PubMed

Yoshida, Yasukazu; Hayakawa, Mieko; Cynshi, Osamu; Jishage, Kou-ichi; Niki, Etsuo

2008-01-01

To assess the antioxidative role of vitamin E (VE) in a mouse model of severe VE deficiency by using biomarkers, alpha-tocopherol transfer protein (alpha-TTP(-/-))-knockout mice were maintained on a VE-deficient diet for 28 weeks [KO group, n = 6]. Wild-type C57BL/6 mice were maintained on a diet containing 0.002% alpha-tocopherol [WT group, n = 6]. The animals were housed individually in a metabolic cage from the age of 9 weeks (Week 0) to 27 weeks. Urine was collected every week, and the levels of total hydroxyoctadecadienoic acid (tHODE), 7-hydroxycholesterol (t7-OHCh), and 8-iso-prostaglandin F(2alpha)(t8-isoPGF(2alpha)), which are biomarkers for lipid peroxidation, were measured by gas chromatography (GC)-mass spectrometry. From the age of 21 weeks (Week 12), three mice in each group were provided drinking water containing the water-soluble radical initiator 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) until the end of the study (Week 19). Blood and tissue samples were collected, and the levels of the abovementioned biomarkers therein were assessed. AIPH consumption clearly elevated the plasma and erythrocyte levels of tHODE and t8-isoPGF(2alpha) in both the WT and KO groups except for the erythrocyte level of tHODE in the WT group. Furthermore, this elevation was more prominent in the KO group than in the WT group. Interestingly, AIPH consumption reduced the stereoisomer ratio of HODE (ZE/EE), which is reflective of the efficacy of a compound as an antioxidant in vivo; this suggests that free radical-mediated oxidation reduces the antioxidant capacity in vivo. The urine levels of tHODE, t7-OHCh, and t8-isoPGF(2alpha) tended to increase with AIPH consumption, but these individual levels fluctuated. It was clearly demonstrated by the proposed biomarkers that maintaining alpha-TTP(-/-) mice on a VE-deficient diet results in a severe VE deficiency and promotes lipid peroxidation.

Modulation by geraniol of gene expression involved in lipid metabolism leading to a reduction of serum-cholesterol and triglyceride levels.

PubMed

Galle, Marianela; Kladniew, Boris Rodenak; Castro, María Agustina; Villegas, Sandra Montero; Lacunza, Ezequiel; Polo, Mónica; de Bravo, Margarita García; Crespo, Rosana

2015-07-15

Geraniol (G) is a natural isoprenoid present in the essential oils of several aromatic plants, with various biochemical and pharmacologic properties. Nevertheless, the mechanisms of action of G on cellular metabolism are largely unknown. We propose that G could be a potential agent for the treatment of hyperlipidemia that could contribute to the prevention of cardiovascular disease. The aim of the present study was to advance our understanding of its mechanism of action on cholesterol and TG metabolism. NIH mice received supplemented diets containing 25, 50, and 75 mmol G/kg chow. After a 3-week treatment, serum total-cholesterol and triglyceride levels were measured by commercial kits and lipid biosynthesis determined by the [(14)C] acetate incorporated into fatty acids plus nonsaponifiable and total hepatic lipids of the mice. The activity of the mRNA encoding HMGCR-the rate-limiting step in cholesterol biosynthesis-along with the enzyme levels and catalysis were assessed by real-time RT-PCR, Western blotting, and HMG-CoA-conversion assays, respectively. In-silico analysis of several genes involved in lipid metabolism and regulated by G in cultured cells was also performed. Finally, the mRNA levels encoded by the genes for the low-density-lipoprotein receptor (LDLR), the sterol-regulatory-element-binding transcription factor (SREBF2), the very-low-density-lipoprotein receptor (VLDLR), and the acetyl-CoA carboxylase (ACACA) were determined by real-time RT-PCR. Plasma total-cholesterol and triglyceride levels plus hepatic fatty-acid, total-lipid, and nonsaponifiable-lipid biosynthesis were significantly reduced by feeding with G. Even though an up-regulation of the mRNA encoding HMGCR occurred in the G treated mouse livers, the protein levels and specific activity of the enzyme were both inhibited. G also enhanced the mRNAs encoding the LDL and VLDL receptors and reduced ACACA mRNA, without altering the transcription of the mRNA encoding the SREBF2. The following mechanisms may have mediated the decrease in plasma lipids levels in mice: a down-regulation of hepatocyte-cholesterol synthesis occurred as a result of decreased HMGCR protein levels and catalytic activity; the levels of LDLR mRNA became elevated, thus suggesting an increase in the uptake of serum LDL, especially by the liver; and TG synthesis became reduced very likely because of a decrease in fatty-acid synthesis. Copyright © 2015 Elsevier GmbH. All rights reserved.

FADS1 FADS2 Gene Cluster, PUFA Intake and Blood Lipids in Children: Results from the GINIplus and LISAplus Studies

PubMed Central

Standl, Marie; Lattka, Eva; Stach, Barbara; Koletzko, Sibylle; Bauer, Carl-Peter; von Berg, Andrea; Berdel, Dietrich; Krämer, Ursula; Schaaf, Beate; Röder, Stefan; Herbarth, Olf; Buyken, Anette; Drogies, Tim; Thiery, Joachim; Koletzko, Berthold; Heinrich, Joachim

2012-01-01

Background Elevated cholesterol levels in children can be a risk factor for cardiovascular diseases in later life. In adults, it has been shown that blood lipid levels are strongly influenced by polymorphisms in the fatty acid desaturase (FADS) gene cluster in addition to nutritional and other exogenous and endogenous determinants. Our aim was to investigate whether lipid levels are determined by the FADS genotype already in children and whether this association interacts with dietary intake of n-3 fatty acids. Methods The analysis was based on data of 2006 children from two German prospective birth cohort studies. Total cholesterol, HDL, LDL and triglycerides were measured at 10 years of age. Six single nucleotide polymorphisms (SNPs) of the FADS gene cluster were genotyped. Dietary n-3 fatty acid intake was assessed by food frequency questionnaire. Linear regression modeling was used to assess the association between lipid levels, n-3 fatty acid intake and FADS genotype. Results Individuals carrying the homozygous minor allele had lower levels of total cholesterol [means ratio (MR) ranging from 0.96 (p = 0.0093) to 0.98 (p = 0.2949), depending on SNPs] and LDL [MR between 0.94 (p = 0.0179) and 0.97 (p = 0.2963)] compared to homozygous major allele carriers. Carriers of the heterozygous allele showed lower HDL levels [β between −0.04 (p = 0.0074) to −0.01 (p = 0.3318)] and higher triglyceride levels [MR ranging from 1.06 (p = 0.0065) to 1.07 (p = 0.0028)] compared to homozygous major allele carriers. A higher n-3 PUFA intake was associated with higher concentrations of total cholesterol, LDL, HDL and lower triglyceride levels, but these associations did not interact with the FADS1 FADS2 genotype. Conclusion Total cholesterol, HDL, LDL and triglyceride concentrations may be influenced by the FADS1 FADS2 genotype already in 10 year old children. Genetically determined blood lipid levels during childhood might differentially predispose individuals to the development of cardiovascular diseases later in life. PMID:22629455

The effect of prolactin levels on MPV in women with PCOS.

PubMed

Yilmaz, Özgür; Calan, Mehmet; Kume, Tuncay; Temur, Muzaffer; Yesil, Pınar; Senses, Mehmet Y

2015-05-01

Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk factors including hypertension, obesity, hyperlipidaemia and glucose intolerance. Several studies demonstrated the link between PCOS and an increased risk of cardiovascular disease. Platelets play a crucial role in the development of atherothrombotic disease. Mean platelet volume (MPV) is a marker of platelet size that reflects its activity. Research points to a link between prolactin (PRL) and platelet activation. The purpose of this study was to investigate whether prolactin levels are associated with MPV in women with PCOS. The research was designed as a cross-sectional study. Participants were divided into three groups-PCOS patients with mildly elevated PRL levels (n = 72), patients with PCOS with normal PRL levels (n = 207) and healthy controls (n = 90). They were body mass index and age-matched and consecutively recruited. Complete blood counts, serum glucose, prolactin, insulin, lipids, high-sensitivity C-reactive protein and free-testosterone levels were measured. Among the three groups, MPV levels were higher in women with PCOS having mildly elevated PRL levels (P < 0·001) and MPV was found to be correlated with PRL levels (r = 0·387, P < 0·001). Multiple regression analysis showed that PRL levels were associated with MPV levels (R(2) = 0·239, β = 0·354, P < 0·001). Mean platelet volume levels are significantly increased in women with PCOS having mildly elevated PRL. Our results suggest that there is a link between prolactin and MPV levels. In women with PCOS, elevated PRL levels may increase the risk of developing atherothrombotic events via the activation of platelets. © 2014 John Wiley & Sons Ltd.

Genetic predisposition to increased blood cholesterol and triglyceride lipid levels and risk of Alzheimer disease: a Mendelian randomization analysis.

PubMed

Proitsi, Petroula; Lupton, Michelle K; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F

2014-09-01

Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n=10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10-8 and trait specific scores using SNPs associated exclusively with each trait at p<5 × 10-8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR]=1.005, 95% CI 0.82-1.24, p = 0.962 per 1 unit increase in HDL-c; OR=0.901, 95% CI 0.65-1.25, p=0.530 per 1 unit increase in LDL-c; OR=1.104, 95% CI 0.89-1.37, p=0.362 per 1 unit increase in triglycerides; and OR=0.954, 95% CI 0.76-1.21, p=0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD. Please see later in the article for the Editors' Summary.

BCAA Metabolism and Insulin Sensitivity - Dysregulated by Metabolic Status?

PubMed

Gannon, Nicholas P; Schnuck, Jamie K; Vaughan, Roger A

2018-03-01

Branched-chain amino acids (BCAAs) appear to influence several synthetic and catabolic cellular signaling cascades leading to altered phenotypes in mammals. BCAAs are most notably known to increase protein synthesis through modulating protein translation, explaining their appeal to resistance and endurance athletes for muscle hypertrophy, expedited recovery, and preservation of lean body mass. In addition to anabolic effects, BCAAs may increase mitochondrial content in skeletal muscle and adipocytes, possibly enhancing oxidative capacity. However, elevated circulating BCAA levels have been correlated with severity of insulin resistance. It is hypothesized that elevated circulating BCAAs observed in insulin resistance may result from dysregulated BCAA degradation. This review summarizes original reports that investigated the ability of BCAAs to alter glucose uptake in consequential cell types and experimental models. The review also discusses the interplay of BCAAs with other metabolic factors, and the role of excess lipid (and possibly energy excess) in the dysregulation of BCAA catabolism. Lastly, this article provides a working hypothesis of the mechanism(s) by which lipids may contribute to altered BCAA catabolism, which often accompanies metabolic disease. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-steatotic and anti-inflammatory roles of syringic acid in high-fat diet-induced obese mice.

PubMed

Ham, Ju Ri; Lee, Hae-In; Choi, Ra-Yeong; Sim, Mi-Ok; Seo, Kwon-Il; Lee, Mi-Kyung

2016-02-01

This study examined the effects of syringic acid (SA) on obese diet-induced hepatic dysfunction. Mice were fed high-fat diet (HFD) with or without SA (0.05%, wt/wt) for 16 weeks. SA reduced the body weight, visceral fat mass, serum levels of leptin, TNFα, IFNγ, IL-6 and MCP-1, insulin resistance, hepatic lipid content, droplets and early fibrosis, whereas it elevated the circulation of adiponectin. SA down-regulated lipogenic genes (Cidea, Pparγ, Srebp-1c, Srebp-2, Hmgcr, Fasn) and inflammatory genes (Tlr4, Myd88, NF-κB, Tnfα, Il6), whereas it up-regulated fatty acid oxidation genes (Pparα, Acsl, Cpt1, Cpt2) in the liver. SA also decreased hepatic lipogenic enzyme activities and elevated fatty acid oxidation enzyme activities relative to the HFD group. These findings suggested that dietary SA possesses anti-obesity, anti-inflammatory and anti-steatotic effects via the regulation of lipid metabolic and inflammatory genes. SA is likely to be a new natural therapeutic agent for obesity or non-alcoholic liver disease.

Dyslipidemia in subclinical hypothyroidism requires assessment of small dense low density lipoprotein cholesterol (sdLDL-C).

PubMed

Saric, Maida Seferovic; Jurasic, Miljenka-Jelena; Sovic, Slavica; Kranjcec, Bojana; Glivetic, Tatjana; Demarin, Vida

2017-09-26

Usually both hypothyroidism and hyperthyroidism are related to the cardiovascular and cerebrovascular disease development. The relationship between subclinical hypothyroidism has been widely investigated but the findings remain controversial. The aim of the present study was to evaluate the lipid profile in patients with subclinical hypothyroidism (SHypo) in comparison to controls and to determine the association of SHypo and dyslipidemia in attempt to find importance of small dense low-density lipoprotein cholesterol (sdLDL-C) in atherosclerosis. In this study we included 100 women, aged 30 to 70 years that were divided into subgroups according to their age. According to the values of levels of thyroid hormones they were divided into euthyroid (control) group (n = 64) and (newly discovered) subclinical hypothyroidism (SHypo) group (n = 36). A high-sensitivity C-reactive protein (hs-CRP) and lipid profile, including small dense low-density lipoprotein cholesterol (sdLDL-C) were determined. Body weight and height were measured and BMI calculated. History of the current illness, medication, alcohol consumption and cigarettes smoking were noted. Changed lipid profile as well as elevated triglycerides and sdLDL-C were observed in the group with subclinical hypothyroidism compared to the control group. It is important to determine serum lipid levels, especially serum sdLDL-C levels at an early stage of subclinical hypothyroidism, since they represent atherogenic LDL particles and are better indicators for dyslipidaemia in subclinical hypothyroidism and the development of atherosclerosis with potential complications such as cardiovascular and cerebrovascular diseases.

Non-traditional Serum Lipid Variables and Recurrent Stroke Risk

PubMed Central

Park, Jong-Ho; Lee, Juneyoung; Ovbiagele, Bruce

2014-01-01

Background and Purpose Expert consensus guidelines recommend low-density lipoprotein cholesterol (LDL-C) as the primary serum lipid target for recurrent stroke risk reduction. However, mounting evidence suggests that other lipid parameters might be additional therapeutic targets or at least also predict cardiovascular risk. Little is known about the effects of non-traditional lipid variables on recurrent stroke risk. Methods We analyzed the Vitamin Intervention for Stroke Prevention study database comprising 3680 recent (<120 days) ischemic stroke patients followed up for 2 years. Independent associations of baseline serum lipid variables with recurrent ischemic stroke (primary outcome) and the composite endpoint of ischemic stroke/coronary heart disease (CHD)/vascular death (secondary outcomes) were assessed. Results Of all variables evaluated, only triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio was consistently and independently related to both outcomes: compared with the lowest quintile, the highest TG/HDL-C ratio quintile was associated with stroke (adjusted hazard ratio, 1.56; 95% CI, 1.05−2.32) and stroke/CHD/vascular death (1.39; 1.05−1.83), including adjustment for lipid modifier use. Compared with the lowest quintile, the highest total cholesterol/HDL-C ratio quintile was associated with stroke/CHD/vascular death (1.45; 1.03−2.03). LDL-C/HDL-C ratio, non-HDL-C, elevated TG alone, and low HDL-C alone were not independently linked to either outcome. Conclusions Of various non-traditional lipid variables, elevated baseline TG/HDL-C and TC/HDL-C ratios predict future vascular risk after a stroke, but only elevated TG/HDL-C ratio is related to risk of recurrent stroke. Future studies should assess the role of TG/HDL as a potential therapeutic target for global vascular risk reduction after stroke. PMID:25236873

Lysophosphatidic Acid and Apolipoprotein A1 Predict Increased Risk of Developing World Trade Center Lung Injury: A Nested Case-Control Study

PubMed Central

Tsukiji, Jun; Cho, Soo Jung; Echevarria, Ghislaine C.; Kwon, Sophia; Joseph, Phillip; Schenck, Edward J.; Naveed, Bushra; Prezant, David J.; Rom, William N.; Schmidt, Ann Marie; Weiden, Michael D.; Nolan, Anna

2014-01-01

Rationale Metabolic syndrome, inflammatory and vascular injury markers measured in serum after WTC exposures predict abnormal FEV1. We hypothesized that elevated LPA levels predict FEV1

Localization of 1-deoxysphingolipids to mitochondria induces mitochondrial dysfunction.

PubMed

Alecu, Irina; Tedeschi, Andrea; Behler, Natascha; Wunderling, Klaus; Lamberz, Christian; Lauterbach, Mario A R; Gaebler, Anne; Ernst, Daniela; Van Veldhoven, Paul P; Al-Amoudi, Ashraf; Latz, Eicke; Othman, Alaa; Kuerschner, Lars; Hornemann, Thorsten; Bradke, Frank; Thiele, Christoph; Penno, Anke

2017-01-01

1-Deoxysphingolipids (deoxySLs) are atypical sphingolipids that are elevated in the plasma of patients with type 2 diabetes and hereditary sensory and autonomic neuropathy type 1 (HSAN1). Clinically, diabetic neuropathy and HSAN1 are very similar, suggesting the involvement of deoxySLs in the pathology of both diseases. However, very little is known about the biology of these lipids and the underlying pathomechanism. We synthesized an alkyne analog of 1-deoxysphinganine (doxSA), the metabolic precursor of all deoxySLs, to trace the metabolism and localization of deoxySLs. Our results indicate that the metabolism of these lipids is restricted to only some lipid species and that they are not converted to canonical sphingolipids or fatty acids. Furthermore, exogenously added alkyne-doxSA [(2S,3R)-2-aminooctadec-17-yn-3-ol] localized to mitochondria, causing mitochondrial fragmentation and dysfunction. The induced mitochondrial toxicity was also shown for natural doxSA, but not for sphinganine, and was rescued by inhibition of ceramide synthase activity. Our findings therefore indicate that mitochondrial enrichment of an N-acylated doxSA metabolite may contribute to the neurotoxicity seen in diabetic neuropathy and HSAN1. Hence, we provide a potential explanation for the characteristic vulnerability of peripheral nerves to elevated levels of deoxySLs. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Single cell assessment of yeast metabolic engineering for enhanced lipid production using Raman and AFM-IR imaging.

PubMed

Kochan, Kamila; Peng, Huadong; Wood, Bayden R; Haritos, Victoria S

2018-01-01

Biodiesel is a valuable renewable fuel made from derivatized fatty acids produced in plants, animals, and oleaginous microbes. Of the latter, yeasts are of special interest due to their wide use in biotechnology, ability to synthesize fatty acids and store large amounts of triacylglycerols while utilizing non-food carbon sources. While yeast efficiently produce lipids, genetic modification and indeed, lipid pathway metabolic engineering, is usually required for cost-effective production. Traditionally, gas chromatography (GC) is used to measure fatty acid production and to track the success of a metabolic engineering strategy in a microbial culture; here we have employed vibrational spectroscopy approaches at population and single cell level of engineered yeast while simultaneously investigating metabolite levels in subcellular structures. Firstly, a strong correlation ( r 2  > 0.99) was established between Fourier transform infrared (FTIR) lipid in intact cells and GC analysis of fatty acid methyl esters in the differently engineered strains. Confocal Raman spectroscopy of individual cells carrying genetic modifications to enhance fatty acid synthesis and lipid accumulation revealed changes to the lipid body (LB), the storage organelle for lipids in yeast, with their number increasing markedly (up to tenfold higher); LB size was almost double in the strain that also expressed a LB stabilizing gene but considerable variation was also noted between cells. Raman spectroscopy revealed a clear trend toward reduced unsaturated fatty acid content in lipids of cells carrying more complex metabolic engineering. Atomic force microscopy-infrared spectroscopy (AFM-IR) analysis of individual cells indicated large differences in subcellular constituents between strains: cells of the most highly engineered strain had elevated lipid and much reduced carbohydrate in their cytoplasm compared with unmodified cells. Vibrational spectroscopy analysis allowed the simultaneous measurement of strain variability in metabolite production and impact on cellular structures as a result of different gene introductions or knockouts, within a lipid metabolic engineering strategy and these inform the next steps in comprehensive lipid engineering. Additionally, single cell spectroscopic analysis measures heterogeneity in metabolite production across microbial cultures under genetic modification, an emerging issue for efficient biotechnological production.

[Specifics of hormonal and energy balance in patients with hyperplasia and endometrial neoplasia with metabolic syndrome in the background].

PubMed

Chernyshova, A L; Kolomiets, L A; Bochkarëva, N V; Kondakova, I V

2013-01-01

We conducted a comparative investigation of the hormonal status (LH, FSH, estradiol, progesterone, testosterone, prolactin, SHBG), energy status (leptin, ghrelin, insulin), and carbohydrate and lipid metabolism in patients with endometrial hyperplasia and neoplasia (168 patients) with or without metabolic syndrome in the background. Patients with metabolic syndrome had a high frequency of elevated estrogen (72%), testosterone (65%), insulin (81%), leptin (68%). There was a marked increase in the basal level of luteinizing hormone, prolactin, index, LH/FSH, but decrease in FSH and progesterone. There were significant changes in carbohydrate and lipid metabolism. The possible mechanisms for the contribution of the investigated factors to the development of the pathological processes in the endometrium are presented.

Autoxidation products of both carbohydrates and lipids are increased in uremic plasma: is there oxidative stress in uremia?

PubMed

Miyata, T; Fu, M X; Kurokawa, K; van Ypersele de Strihou, C; Thorpe, S R; Baynes, J W

1998-10-01

Advanced glycation end products (AGEs), formed by non-enzymatic glycation and oxidation (glycoxidation) reactions, have been implicated in the pathogenesis of several diseases, including normoglycemic uremia. AGE research in uremia has focused on the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recent studies, however, have demonstrated that one AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fatty acids in vitro, raising the possibility that both carbohydrate and lipid autoxidation might be increased in uremia. To address this hypothesis, we applied gas chromatography-mass spectrometry and high performance liquid chromatography to measure protein adducts formed in uremic plasma by reactions between carbonyl compounds and protein amino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and CML originating possibly from both sources. All three adducts were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with fructoselysine levels and were similar in diabetic and non-diabetic patients on hemodialysis, indicating that their increase was not driven by glucose. Pentosidine and MDA-lysine were also increased in plasma to the same extent in diabetic and non-diabetic hemodialysis patients. Statistical analysis indicated that plasma levels of CML correlated weakly (P < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine and MDA-lysine varied independently (P > 0.5). These data suggest that the increased levels of AGEs in blood, and probably in tissues, reported in uremia implicate a broad derangement in non-enzymatic biochemistry involving alterations in autoxidation of both carbohydrates and lipids.

High plasma level of remnant-like particle cholesterol in the metabolic syndrome.

PubMed

Satoh, Akira; Adachi, Hisashi; Tsuruta, Makoto; Hirai, Yuji; Hiratsuka, Akiko; Enomoto, Mika; Furuki, Kumiko; Hino, Asuka; Takeuchi, Tomohiro; Imaizumi, Tsutomu

2005-10-01

The metabolic syndrome is associated with a high incidence of cardiovascular disease even when the abnormalities present in the syndrome are mild. The underlying mechanism of the metabolic syndrome has not been elucidated. We investigated whether a strong atherogenic lipoprotein, remnant-like particle (RLP) lipoprotein cholesterol, is elevated in the metabolic syndrome. We performed a health examination among the residents of a rural community in Japan. Complete datasets, including fasting RLP cholesterol levels, were obtained in 1,261 subjects (509 men and 752 women) without diabetes and who were not taking lipid-lowering drugs. The subjects' medical history, use of alcohol, and smoking habits were ascertained by a questionnaire. All of the components of the metabolic syndrome were significantly related to RLP cholesterol by univariate analysis. Total cholesterol and smoking habits were also positively associated with RLP cholesterol. The subjects with the metabolic syndrome showed only mild abnormalities of each component. When RLP cholesterol levels were stratified by the number of the components of the metabolic syndrome, there was a strong association between RLP cholesterol levels and the number of components (P < 0.001 and F = 72.7). RLP cholesterol levels are elevated in the metabolic syndrome, and this elevation may underlie the high incidence of cardiovascular disease in the metabolic syndrome.

Oxidative Stress Level in the Testes of Mice and Rats during Nickel Intoxication

PubMed Central

Murawska-Ciałowicz, Eugenia; Bal, Wojciech; Januszewska, Lidia; Zawadzki, Marcin; Rychel, Joanna; Zuwała-Jagiełło, Jolanta

2012-01-01

The genotioxic and carcinogenic effect of nickel probably results from its capacity to produce reactive oxygen species (ROS) and disturb the redox balance. The aim of the study was to find out if rats lacking spermatic protamine 2 are less susceptible to Ni(II) than mice. Consequently, the levels of malondialdehyde + 4 hydroxynonenal (MDA+4HDA) − markers of lipid peroxidation, as well as the level of reduced glutathione (GSH) were measured within the rat and mouse testes. Our results showed that the levels of lipid peroxidation markers were elevated in testicular homogenates of intoxicated mice without any changes in rats. GSH level was lower in the group of intoxicated mice comparing to the control without statistically significant changes in rats' homogenates. Moreover, the level of GSH in the testes of intoxicated mice was lower than in rats. On the basis of our results, it appears that Ni(II) can initiate oxidative stress in the testes of mice but not of rats and can reduce GSH level. Consequently, the antioxidative defense of the testes is reduced. Ni(II) that causes oxidative stress in the testes may also contribute to infertility. PMID:22448131

Chronic Nosema ceranae infection inflicts comprehensive and persistent immunosuppression and accelerated lipid loss in host Apis mellifera honey bees.

PubMed

Li, Wenfeng; Chen, Yanping; Cook, Steven C

2018-05-01

Nosema ceranae is an intracellular microsporidian parasite of the Asian honey bee Apis cerana and the European honey bee Apis mellifera. Until relatively recently, A. mellifera honey bees were naïve to N. ceranae infection. Symptoms of nosemosis, or Nosema disease, in the infected hosts include immunosuppression, damage to gut epithelium, nutrient and energetic stress, precocious foraging and reduced longevity of infected bees. Links remain unclear between immunosuppression, the symptoms of nutrient and energetic stress, and precocious foraging behavior of hosts. To clarify physiological connections, we inoculated newly emerged A. mellifera adult workers with N. ceranae spores, and over 21 days post inoculation (21 days pi), gauged infection intensity and quantified expression of genes representing two innate immune pathways, Toll and Imd. Additionally, we measured each host's whole-body protein, lipids, carbohydrates and quantified respirometric and activity levels. Results show sustained suppression of genes of both humorally regulated immune response pathways after 6 days pi. At 7 days pi, elevated protein levels of infected bees may reflect synthesis of antimicrobial peptides from an initial immune response, but the lack of protein gain compared with uninfected bees at 14 days pi may represent low de novo protein synthesis. Carbohydrate data do not indicate that hosts experience severe metabolic stress related to this nutrient. At 14 days pi infected honey bees show high respirometric and activity levels, and corresponding lipid loss, suggesting lipids may be used as fuel for increased metabolic demands resulting from infection. Accelerated lipid loss during nurse honey bee behavioral development can have cascading effects on downstream physiology that may lead to precocious foraging, which is a major factor driving colony collapse. Published by Elsevier Ltd.

Interannual variations in the lipids of the Antarctic pteropods Clione limacina and Clio pyramidata.

PubMed

Phleger, C F; Nelson, M M; Mooney, B D; Nichols, P D

2001-03-01

Antarctic pteropods, Clione limacina (Order Gymnosomata) and Clio pyramidata (order Thecosomata), were collected near Elephant Island, South Shetland Islands, during 1997 and 1998. Total lipid was high in C. limacina (29--36 mg g(-1) wet mass) and included 46% of diacy1glyceryl ether (DAGE, as % of total lipid) for both 1997 and 1998. DAGE was not detected in C. pyramidata, which had mainly polar lipid and triacy1glycerol. 1-O-Alkyl glyceryl ethers (GE) derived from the DAGE consisted primarily of 15:0 and 16:0, with lower 17:0 and a17:0. The principal sterols of both pteropods included trans-dehydrocholesterol, brassicasterol, 24-methylenecholesterol, cholesterol and desmosterol. Levels of 24-methylenecholesterol and desmosterol were lower in both pteropods in 1997 compared to 1998. C. limacina had high levels of the odd-chain fatty acids 17:1(n--8)c and 15:0 in contrast to C. pyramidata. The previously proposed source of elevated odd-chain fatty acids in C. limacina is via propionate derived from phytoplankton DMPT; another possible source may be from thraustochytrids, which are common marine microheterotrophs. C. pyramidata had twice as much PUFA as C. limacina, largely due to higher 20:5(n--3). The PUFA 18:5(n--3) and very long chain fatty acids (C(24), C(26) and C(28) VLC-PUFA) were only detected in 1998 pteropods. In comparison, 1996 samples of C. limacina contained lower DAGE levels, which also may reflect differences in diet and oceanographic conditions. Interannual variations in specific lipid biomarkers are discussed with respect to possible different phytoplankton food sources available in the AMLR survey area.

Inflammatory Markers and Plasma Lipids in HIV Patients: A Correlation Analysis Study

PubMed Central

Muswe, Rudo; Oktedalen, Olav; Zhou, Danai T.; Zinyando, Enita; Shawarira-Bote, Sandra; Stray-Pedersen, Babill; Siziba, Atipa; Gomo, Zvenyika A.R.

2017-01-01

Background: Recent evidence suggests that HIV infection, even with treatment, increases the risk of coronary heart disease (CHD) and that both chronic inflammation and traditional risk factors play key roles in HIV-associated CHD. Subjects and Methods: Patients (N=152), attending Harare HIV clinic, 26% of them male and 82% of them on antiretroviral therapy (ART), were studied. Inflammatory markers comprising of cytokines such as pro-inflammatory tumor necrosis factor-α, (TNF-α), anti-inflammatory interleukin 10, (IL-10) and highly sensitive C reactive protein (hsCRP) together with lipids were assayed using enzyme linked immunosorbent assay (ELISA), immuno-turbidimetric and enzymatic assays, respectively. Correlation analysis of inflammatory markers versus lipid profiles was carried out using bivariate regression analysis. Results: Anti-inflammatory cytokine IL-10 and inflammatory hsCRP levels were elevated when measured in all the HIV positive patients, while TNF-α and lipid levels were within normal ranges. Pro-inflammatory TNF-α was significantly higher in ART-naive patients than ART-experienced patients, whereas the reverse was observed for anti-inflammatory IL-10 and anti-atherogenic HDL-C. Correlation analysis indicated a significant positive linear association between IL-10 and total cholesterol (TC) levels but no other correlations were found. Conclusion: High cytokine ratio (TNF-α/IL-10) indicates higher CHD risk in ART-naive patients compared to the ART-exposed. The CHD risk could be further strengthened by interplay between inflammatory markers and high prevalence of low HDL-C. Lack of correlation between pro-inflammatory markers (hsCRP and TNF-α) with lipid fractions and correlation between anti-inflammatory IL-10 with artherogenic TC were unexpected findings, necessitating further studies in future. PMID:29387269

Hepatoprotective effects of Nigella sativa L and Urtica dioica L on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats

PubMed Central

Kanter, Mehmet; Coskun, Omer; Budancamanak, Mustafa

2005-01-01

AIM: To investigate the effects of Nigella sativa L (NS) and Urtica dioica L (UD) on lipid peroxidation, antioxidant enzyme systems and liver enzymes in CCl4-treated rats. METHODS: Fifty-six healthy male Wistar albino rats were used in this study. The rats were randomly allotted into one of the four experimental groups: A (CCl4-only treated), B (CCl4+UD treated), C (CCl4+NS treated) and D (CCl4+UD+NS treated), each containing 14 animals. All groups received CCl4 (0.8 mL/kg of body weight, sc, twice a week for 60 d). In addition, B, C and D groups also received daily i.p. injections of 0.2 mL/kg NS or/and 2 mL/kg UD oils for 60 d. Group A, on the other hand, received only 2 mL/kg normal saline solution for 60 d. Blood samples for the biochemical analysis were taken by cardiac puncture from randomly chosen-seven rats in each treatment group at beginning and on the 60th d of the experiment. RESULTS: The CCl4 treatment for 60 d increased the lipid peroxidation and liver enzymes, and also decreased the antioxidant enzyme levels. NS or UD treatment (alone or combination) for 60 d decreased the elevated lipid peroxidation and liver enzyme levels and also increased the reduced antioxidant enzyme levels. The weight of rats decreased in group A, and increased in groups B, C and D. CONCLUSION: NS and UD decrease the lipid per-oxidation and liver enzymes, and increase the anti-oxidant defense system activity in the CCl4-treated rats. PMID:16425366

Elevated ambulatory blood pressure in a multi-ethnic population of obese children and adolescents.

PubMed

Aguilar, Alexandra; Ostrow, Vlady; De Luca, Francesco; Suarez, Elizabeth

2010-06-01

To evaluate the relationship among ambulatory blood pressure (ABP), body mass index (BMI), and homeostasis model assessment (HOMA) in a multi-ethnic population of obese children with clinic blood pressure in the reference range. A total of 43 obese normotensive children (7-17 years old) were recruited. ABP monitoring, oral glucose tolerance test, lipid levels, and urine microalbumin levels were obtained. Fourteen percent of the subjects had elevated 24-hour systolic blood pressure (SBP), 9.3% had elevated daytime SBP, and 32.6 % elevated nighttime SBP. For diastolic blood pressure, 4.7% of the sample had an elevated mean nighttime value. Children with more severe obesity (BMI SD score >2.5) had higher 24-hour and nighttime SBP than children with less severe obesity (BMI SD score < or =2.5). Children with HOMA values in the highest quartile had larger waist circumference and higher clinic blood pressure than children with HOMA values in the lowest quartile, and no difference in the mean ABP values was found in the 2 groups . Multiple linear regression analysis showed that 24-hour and nighttime SBP were significantly correlated with BMI SD score. Obese children with normal clinic blood pressure often exhibit elevated ABP. The risk for ambulatory hypertension appears to be correlated with the degree of obesity. Copyright 2010 Mosby, Inc. All rights reserved.

Preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats.

PubMed

Roy, Abhro Jyoti; Stanely Mainzen Prince, P

2013-10-01

The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100mg/kg body weight) on 8th and 9th day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dyslipidemia and cardiovascular disease risk factor management in HIV-1-infected subjects treated with HAART in the Spanish VACH cohort.

PubMed

Pere, Domingo; Ignacio, Suarez-Lozano; Ramón, Teira; Fernando, Lozano; Alberto, Terrón; Pompeyo, Viciana; Juan, González; M José, Galindo; Paloma, Geijo; Antonio, Vergara; Jaime, Cosín; Esteban, Ribera; Bernardino, Roca; M Luisa, Garcia-Alcalde; Trinitario, Sánchez; Ferran, Torres; Juan Ramón, Lacalle; Myriam, Garrido

2008-01-01

There is increasing evidence that metabolic adverse effects associated with antiretroviral therapy may translate into an increased cardiovascular risk in HIV-1-infected patients. To determine the prevalence of risk factors for cardiovascular disease (CVD) among HIV-1-infected persons, and to investigate any association between them, stage of HIV-1 disease, and use of antiretroviral therapies. Multicentric, cross-sectional analysis of CVD risk factors of treated patients in the VACH cohort. The data collected includes: demographic variables, cigarette smoking, diabetes mellitus, hypertension, dyslipidemia, body mass index, stage of HIV-1 infection, and antiretroviral therapy. The analysis included 2358 patients. More than 18% of the study population was at an age of appreciable risk of CVD. 1.7% had previous CVD and 59.2% were smokers. Increased prevalence of elevated total cholesterol was observed among subjects receiving an NNRTI but no PI [odds ratio (OR), 3.34; 95% confidence interval (CI), 1.77-6.31], PI but no NNRTI (OR, 4.04; 95% CI, 2.12-7.71), or NNRTI + PI (OR, 17.77; 95% CI, 7.24-43.59) compared to patients treated only with nucleoside reverse transcriptase inhibitors (NRTI). Higher CD4 cell count, lower plasma HIV-1 RNA levels, clinical signs of lipodystrophy, longer exposure times to NNRTI and PI, and older age were all also associated with elevated cholesterol levels. The use of lipid lowering agents was very low among our patients. Patients in the VACH cohort present multiple known risk factors for CVD, and a very low rate of lipid lowering therapy use. NNRTI and/or PI-based antiretroviral therapies are associated with the worst lipid profile. This is more frequent in older subjects with greater CD4 counts and controlled HIV-1 replication.

Vascular effects of intravenous intralipid and dextrose infusions in obese subjects

PubMed Central

Gosmanov, Aidar R.; Smiley, Dawn D.; Peng, Limin; Siquiera, Joselita; Robalino, Gonzalo; Newton, Christopher; Umpierrez, Guillermo E.

2013-01-01

Hyperglycemia and elevated free fatty acids (FFA) are implicated in the development of endothelial dysfunction. Infusion of soy-bean oil-based lipid emulsion (Intralipid®) increases FFA levels and results in elevation of blood pressure (BP) and endothelial dysfunction in obese healthy subjects. The effects of combined hyperglycemia and high FFA on BP, endothelial function and carbohydrate metabolism are not known. Twelve obese healthy subjects received four random, 8-h IV infusions of saline, Intralipid 40 mL/h, Dextrose 10% 40 mL/h, or combined Intralipid and dextrose. Plasma levels of FFA increased by 1.03±0.34 mmol/L (p=0.009) after Intralipid, but FFAs remained unchanged during saline, dextrose, and combined Intralipid and dextrose infusion. Plasma glucose and insulin concentrations significantly increased after dextrose and combined Intralipid and dextrose (all, p<0.05) and were not different from baseline during saline and lipid infusion. Intralipid increased systolic BP by 12±9 mmHg (p<0.001) and diastolic BP by 5±6 mmHg (p=0.022), and decreased flow-mediated dilatation (FMD) from baseline by 3.2%±1.4% (p<0.001). Saline and dextrose infusion had neutral effects on BP and FMD. The co-administration of lipid and dextrose decreased FMD by 2.4%±2.1% (p=0.002) from baseline, but did not significantly increase systolic or diastolic BP. Short-term Intralipid infusion significantly increased FFA and BP; in contrast, FFA and BP were unchanged during combined infusion of Intralipid and dextrose. Combined Intralipid and dextrose infusion resulted in endothelial dysfunction similar to Intralipid alone. PMID:22483976

Microparticles (CD146) and Arterial Stiffness Versus Carotid Intima Media Thickness as an Early Predictors of Vascular Affection in Systemic Lupus Patients.

PubMed

Nassef, Sahar; El Guindey, Hala; Fawzy, Mary; Nasser, Amal; Reffai, Rasha; Shemiy, Doa

2016-03-01

This study aims to evaluate cluster of differentiation 146 (CD146) and pulse wave velocity (PWV) as non-invasive methods for prediction of early vascular affection in systemic lupus erythematosus (SLE) patients without symptoms of vascular disease, to detect the outcome and reproducibility of these methods, and to correlate CD146 and PWV with lipid profile, intima media thickness (IMT), and ankle brachial index. Thirty female SLE patients (mean age 26.6±6.6 years; range 15 to 35 years) fulfilling the American College of Rheumatology 1997 revised criteria for SLE classification, and 15 age and sex matched healthy controls were included. All participants were performed full clinical assessments including measurement of Systemic Lupus Erythematosus Disease Activity Index, lipid profile, CD146, carotid IMT, PWV, and rise time as an indication of how fast the waveform rises. Cluster of differentiation 146 levels were elevated in patients with SLE compared to controls (p<0.001). There was a statistically significant difference between patients and controls in the femoral, lower thigh, and ankle rise time. There was a statistically significant correlation between IMT and ages of patients, Systemic Lupus Erythematosus Disease Activity Index, and brachial-below knee PWV, while there was no correlation between IMT and disease duration, lipid profile, brachial-femoral PWV, and brachial-ankle PWV. There was statistically significant correlations between brachial-femoral PWV and serum cholesterol level, and between brachial-ankle PWV and low density lipoprotein cholesterol. Our results showed that SLE vascular affection is more pronounced in small arteries. Also, elevated CD146 and brachial-femoral PWV are useful early markers of vascular affection in SLE as well as rise time may be a marker for arterial stiffness.

Accumulation of electrophilic aldehydes during postovulatory aging of mouse oocytes causes reduced fertility, oxidative stress, and apoptosis.

PubMed

Lord, Tessa; Martin, Jacinta H; Aitken, R John

2015-02-01

With increasing periods of time following ovulation, the metaphase II (MII)-stage oocyte experiences overproduction of reactive oxygen species and elevated levels of lipid peroxidation that are implicitly linked with functional deficiencies acquired during postovulatory oocyte aging. We have demonstrated that the electrophilic aldehydes 4-hydroxynonenal (4HNE), malondialdehyde, and acrolein are by-products of nonenzymatic lipid peroxidation in the murine MII-stage oocyte, adducting to multiple proteins within the cell. The covalent modification of oocyte proteins by these aldehydes increased with extended periods of time postovulation; the mitochondrial protein succinate dehydrogenase (SDHA) was identified as a primary target for 4HNE adduction. Time- and dose-dependent studies revealed that exposure to elevated levels of electrophilic aldehydes causes mitochondrial reactive oxygen species production, lipid peroxidation, loss of mitochondrial membrane potential, and eventual apoptosis within the MII oocyte, presumably as a consequence of electron transport chain collapse following SDHA adduction. Additionally, we have determined that short-term exposure to low doses of 4HNE dramatically impairs the oocyte's ability to participate in fertilization and support embryonic development; however, this loss of functionality can be prevented by supplementation with the antioxidant penicillamine. In conclusion, this study has revealed that the accumulation of electrophilic aldehydes is linked to postovulatory oocyte aging, causing reduced fertility, oxidative stress, and apoptosis of this highly specialized cell. These data highlight the importance of timely fertilization of the mammalian oocyte postovulation and emphasize the potential advantages associated with antioxidant supplementation of oocyte culture medium in circumstances where reinsemination of oocytes may be desirable (i.e., rescue intracytoplasmic sperm injection), or where in vitro fertilization may be delayed. © 2015 by the Society for the Study of Reproduction, Inc.

Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery.

PubMed

Kurhe, Yeshwant; Mahesh, Radhakrishnan; Gupta, Deepali; Thangaraj, Devadoss

2015-01-01

The inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HT3 receptor antagonist (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a) on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alterations. Animals were subjected to different stressors for a period of 28 days. On day 15 after the subsequent stress procedure, mice were administered with (4a) (2 and 4 mg/kg p.o.), escitalopram (10 mg/kg p.o.), or vehicle (10 mL/kg p.o.) until day 28 along with the CUMS. Thereafter, behavioral battery tests like locomotor score, sucrose preference test, forced swim test (FST), tail suspension test (TST), and elevated plus maze (EPM) were performed. Biochemical assays like lipid peroxidation, nitrite levels, reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) were estimated in the mice brain homogenate. (4a) Dose dependently attenuated the behavioral alterations by increasing the sucrose consumption, reducing the immobility time in FST and TST, increasing the open arm number of entries and time in EPM. Furthermore, biochemical alterations were reversed by (4a) as examined by reduced lipid peroxidation and nitrite levels and elevated antioxidant enzyme levels like GSH, catalase and SOD. (4a) exhibits antidepressant potential by reversing the CUMS induced behavioral and biochemical changes in mice.

Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

PubMed

Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

2013-09-01

The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

Impact of different wort boiling temperatures on the beer foam stabilizing properties of lipid transfer protein 1.

PubMed

Van Nierop, Sandra N E; Evans, David E; Axcell, Barry C; Cantrell, Ian C; Rautenbach, Marina

2004-05-19

Beer consumers demand satisfactory and consistent foam stability; thus, it is a high priority for brewers. Beer foam is stabilized by the interaction between certain beer proteins, including lipid transfer protein 1 (LTP1), and isomerized hop alpha-acids, but destabilized by lipids. In this study it was shown that the wort boiling temperature during the brewing process was critical in determining the final beer LTP1 content and conformation. LTP1 levels during brewing were measured by an LTP1 ELISA, using antinative barley LTP1 polyclonal antibodies. It was observed that the higher wort boiling temperatures ( approximately 102 degrees C), resulting from low altitude at sea level, reduced the final beer LTP1 level to 2-3 microg/mL, whereas the lower wort boiling temperatures ( approximately 96 degrees C), resulting from higher altitudes (1800 m), produced LTP1 levels between 17 and 35 microg/mL. Low levels of LTP1 in combination with elevated levels of free fatty acids (FFA) resulted in poor foam stability, whereas beer produced with low levels of LTP1 and FFA had satisfactory foam stability. Previous studies indicated the need for LTP1 denaturing to improve its foam stabilizing properties. However, the results presented here show that LTP1 denaturation reduces its ability to act as a binding protein for foam-damaging FFA. These investigations suggest that wort boiling temperature is an important factor in determining the level and conformation of LTP1, thereby favoring satisfactory beer foam stability.

PhosphoLipid transfer protein (PLTP) exerts a direct pro-inflammatory effect on rheumatoid arthritis (RA) fibroblasts-like-synoviocytes (FLS) independently of its lipid transfer activity

PubMed Central

Deckert, Valérie; Daien, Claire I.; Che, Hélène; Elhmioui, Jamila; Lemaire, Stéphanie; Pais de Barros, Jean-Paul; Desrumaux, Catherine; Combe, Bernard; Hahne, Michael; Lagrost, Laurent; Morel, Jacques

2018-01-01

Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease with modification of lipids profile and an increased risk of cardiovascular events related to inflammation. Plasma phospholipid transfer protein (PLTP) exerts a lipid transfer activity through its active form. PLTP can also bind to receptors such as ATP-binding cassette transporter A1 (ABCA1). In addition to its role in lipoprotein metabolism and atherosclerosis, the latest advances came in support of a complex role of PLTP in the regulation of the inflammatory response, both with pro-inflammatory or anti-inflammatory properties. The aim of the present study was to decipher the role of PLTP in joint inflammation and to assess its relevance in the context of RA. PLTP expression was examined by western-blot and by immunochemistry. ABCA1 expression was analyzed by flow cytometry. Lipid transfer activity of PLTP and pro-inflammatory cytokines were measured in sera and synovial fluid (SF) from RA patients and controls (healthy subjects or osteoarthritis patients [OA]). FLS were treated with both lipid-transfer active form and inactive form of recombinant human PLTP. IL-8, IL-6, VEGF and MMP3 produced by FLS were assessed by ELISA, and proliferation by measuring 3H-Thymidine incorporation. RA synovial tissues showed higher PLTP staining than OA and PLTP protein levels were also significantly higher in RA-FLS. In addition, RA, unlike OA patients, displayed elevated levels of PLTP activity in SF, which correlated with pro-inflammatory cytokines. Both lipid-transfer active and inactive forms of PLTP significantly increased the production of cytokines and proliferation of FLS. ABCA1 was expressed on RAFLS and PLTP activated STAT3 pathway. To conclude, PLTP is highly expressed in the joints of RA patients and may directly trigger inflammation and FLS proliferation, independently of its lipid transfer activity. These results suggest a pro-inflammatory role for PLTP in RA. PMID:29565987

Glucosylceramide accumulation is not confined to the lysosome in fibroblasts from patients with Gaucher disease.

PubMed

Fuller, Maria; Rozaklis, Tina; Lovejoy, Melanie; Zarrinkalam, Krystyna; Hopwood, John J; Meikle, Peter J

2008-04-01

Gaucher disease (GD) is an inborn error of glycosphingolipid metabolism resulting from a deficiency of the lysosomal enzyme beta-glucosidase leading to the accumulation of glucosylceramide (GC) in lysosomes of affected cells. In order to determine the effect of GC accumulation on intracellular lipid content in fibroblasts from patients with GD, we measured individual species of ceramide, di- and trihexosylceramide, sphingomyelin, phosphatidylcholine, phosphatidylinositol and phosphatidylglycerol using electrospray ionisation-tandem mass spectrometry. The different subspecies of each lipid class correlated with each other and were summed to give total lipid concentrations. In addition to GC, we also noted secondary elevations in other lipids, especially in type 2 GD. Sub-cellular fractionation showed that GC was not confined to the lysosome but increased throughout the cell. The sequelae of extra-lysosomal accumulation may have implications in the pathogenic mechanisms of GD by interaction with biochemical and metabolic pathways located outside the lysosome. The elevation of ceramide in confluent type 2 GD fibroblasts redistributed from its primary site of accumulation in the lysosome to the endosomal region at four-weeks post-confluence. The accumulation of lipids in the endosome and lysosome suggests both impaired trafficking of lipids and reduced capacity of the lysosome to degrade lipids.

Safety of high volume lipid emulsion infusion: a first approximation of LD50 in rats.

PubMed

Hiller, David B; Di Gregorio, Guido; Kelly, Kemba; Ripper, Richard; Edelman, Lucas; Boumendjel, Redouane; Drasner, Kenneth; Weinberg, Guy L

2010-01-01

Lipid infusion reverses systemic local anesthetic toxicity. The acceptable upper limit for lipid administration is unknown and has direct bearing on clinical management. We hypothesize that high volumes of lipid could have undesirable effects and sought to identify the dose required to kill 50% of the animals (LD(50)) of large volume lipid administration. Intravenous lines and electrocardiogram electrodes were placed in anesthetized, male Sprague-Dawley rats. Twenty percent lipid emulsion (20, 40, 60, or 80 mL/kg) or saline (60 or 80 mL/kg), were administered over 30 mins; lipid dosing was assigned by the Dixon "up-and-down" method. Rats were recovered and observed for 48 hrs then euthanized for histologic analysis of major organs. Three additional rats were administered 60 mL/kg lipid emulsion and euthanized at 1, 4, and 24 hrs to identify progression of organ damage. The maximum likelihood estimate for LD(50) was 67.72 (SE, 10.69) mL/kg. Triglycerides were elevated immediately after infusion but returned to baseline by 48 hrs when laboratory abnormalities included elevated amylase, aspartate aminotransferase, and serum urea nitrogen for all lipid doses. Histologic diagnosis of myocardium, brain, pancreas, and kidneys was normal at all doses. Microscopic abnormalities in lung and liver were observed at 60 and 80 mL/kg; histopathology in the lung and liver was worse at 1 hr than at 4 and 24 hrs. The LD(50) of rapid, high volume lipid infusion is an order of magnitude greater than doses typically used for lipid rescue in humans and supports the safety of lipid infusion at currently recommended doses for toxin-induced cardiac arrest. Lung and liver histopathology was observed at the highest infused volumes.

Beneficial Effects of Pentanema vestitum Linn. Whole Plant on the Glucose and Other Biochemical Parameters of Alloxan Induced Diabetic Rabbits

PubMed Central

Ilahi, Ikram; Asghar, Ali; Ali, Shujat; Khan, Murad; Khan, Nasrullah

2012-01-01

The residents of Lower Dir and Malakand agency, Khyber Pakhtunkhwa, Pakistan, use the dry powder of whole plant of Pentanema vestitum for the treatment of asthma and diabetes. No documented reports are available about the therapeutic action of Pentanema vestitum. The present study was aimed to explore the antihyperglycemic effect of 70% methanol extract of Pentanema vestitum whole plant in glucose-induced nondiabetic hyperglycemic and alloxan-induced diabetic rabbits. During this study, the effects of plant extract on the serum lipid profile, GPT, ALP, bilirubin and creatinine of diabetic rabbits were also studied. The extract of Pentanema vestitum whole plant exhibited significant (P < 0.05) antihyperglycemic activity in glucose-induced hyperglycemic rabbits. Treatment of alloxan-induced diabetic rabbits with extract significantly (P < 0.05) reduced the elevated levels of serum glucose, GPT, ALP, bilirubin and creatinine. During the study of lipid profile, the extract proved to be antihyperlipidemic and HDL boosting in diabetic rabbit models. From the finding of the present research, it was concluded that the 70% methanol extract of Pentanema vestitum whole plant has beneficial effects on serum levels of glucose, lipid profile, GPT, ALP, bilirubin, and creatinine of diabetic rabbits. PMID:23316385

Oral MSG administration alters hepatic expression of genes for lipid and nitrogen metabolism in suckling piglets.

PubMed

Chen, Gang; Zhang, Jun; Zhang, Yuzhe; Liao, Peng; Li, Tiejun; Chen, Lixiang; Yin, Yulong; Wang, Jinquan; Wu, Guoyao

2014-01-01

This experiment was conducted to investigate the effects of oral administration of monosodium glutamate (MSG) on expression of genes for hepatic lipid and nitrogen metabolism in piglets. A total of 24 newborn pigs were assigned randomly into one of four treatments (n = 6/group). The doses of oral MSG administration, given at 8:00 and 18:00 to sow-reared piglets between 0 and 21 days of age, were 0 (control), 0.06 (low dose), 0.5 (intermediate dose), and 1 (high dose) g/kg body weight/day. At the end of the 3-week treatment, serum concentrations of total protein and high-density lipoprotein cholesterol in the intermediate dose group were elevated than those in the control group (P < 0.05). Hepatic mRNA levels for fatty acid synthase, acetyl-coA carboxylase, insulin-like growth factor-1, glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase were higher in the middle-dose group (P < 0.05), compared with the control group. MSG administration did not affect hepatic mRNA levels for hormone-sensitive lipase or carnitine palmitoyl transferase-1. We conclude that oral MSG administration alters hepatic expression of certain genes for lipid and nitrogen metabolism in suckling piglets.

Mitochondrial modulators improve lipid composition and attenuate memory deficits in experimental model of Huntington's disease.

PubMed

Mehrotra, Arpit; Sood, Abhilasha; Sandhir, Rajat

2015-12-01

3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17 days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondria isolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animals had impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA + ALCAR for 21 days normalized mitochondrial lipid composition, improved mitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD.

Protein and lipid damage in maple syrup urine disease patients: l-carnitine effect.

PubMed

Mescka, Caroline Paula; Wayhs, Carlos Alberto Yasin; Vanzin, Camila Simioni; Biancini, Giovana Brondani; Guerreiro, Gilian; Manfredini, Vanusa; Souza, Carolina; Wajner, Moacir; Dutra-Filho, Carlos Severo; Vargas, Carmen Regla

2013-02-01

Maple syrup urine disease (MSUD) is an inborn error of metabolism biochemically characterized by elevated levels of the branched chain amino acids (BCAA) leucine, isoleucine, valine and the corresponding branched-chain α-keto acids. This disorder is clinically characterized by ketoacidosis, seizures, coma, psychomotor delay and mental retardation whose pathophysiology is not completely understood. Recent studies have shown that oxidative stress may be involved in neuropathology of MSUD. l-Carnitine (l-Car) plays a central role in the cellular energy metabolism because it transports long-chain fatty acids for oxidation and ATP generation. In recent years many studies have demonstrated the antioxidant role of this compound. In this work, we investigated the effect of BCAA-restricted diet supplemented or not with l-Car on lipid peroxidation and in protein oxidation in MSUD patients. We found a significant increase of malondialdehyde and of carbonyl content in plasma of MSUD patients under BCAA-restricted diet compared to controls. Furthermore, patients under BCAA-restricted diet plus l-Car supplementation presented a marked reduction of malondialdehyde content in relation to controls, reducing the lipid peroxidation. In addition, free l-Car concentrations were negatively correlated with malondialdehyde levels. Our data show that l-Car may have an antioxidant effect, protecting against the lipid peroxidation and this could represent an additional therapeutic approach to the patients affected by MSUD. Copyright © 2012 ISDN. Published by Elsevier Ltd. All rights reserved.

Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits

PubMed Central

Stavrides, Philip; Saito, Mitsuo; Kumar, Asok; Rodriguez-Navarro, Jose A.; Pawlik, Monika; Huo, Chunfeng; Walkley, Steven U.; Saito, Mariko; Cuervo, Ana M.

2014-01-01

Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimer’s disease and Alzheimer mouse models. We have previously reported that severe lysosomal and amyloid neuropathology and associated cognitive deficits in the TgCRND8 Alzheimer mouse model can be ameliorated by restoring lysosomal proteolytic capacity and autophagy flux via genetic deletion of the lysosomal protease inhibitor, cystatin B. Here we present evidence that macroautophagy is a significant pathway for lipid turnover, which is defective in TgCRND8 brain where lipids accumulate as membranous structures and lipid droplets within giant neuronal autolysosomes. Levels of multiple lipid species including several sphingolipids (ceramide, ganglioside GM3, GM2, GM1, GD3 and GD1a), cardiolipin, cholesterol and cholesteryl esters are elevated in autophagic vacuole fractions and lysosomes isolated from TgCRND8 brain. Lipids are localized in autophagosomes and autolysosomes by double immunofluorescence analyses in wild-type mice and colocalization is increased in TgCRND8 mice where abnormally abundant GM2 ganglioside-positive granules are detected in neuronal lysosomes. Cystatin B deletion in TgCRND8 significantly reduces the number of GM2-positive granules and lowers the levels of GM2 and GM3 in lysosomes, decreases lipofuscin-related autofluorescence, and eliminates giant lipid-containing autolysosomes while increasing numbers of normal-sized autolysosomes/lysosomes with reduced content of undigested components. These findings have identified macroautophagy as a previously unappreciated route for delivering membrane lipids to lysosomes for turnover, a function that has so far been considered to be mediated exclusively through the endocytic pathway, and revealed that autophagic-lysosomal dysfunction in TgCRND8 brain impedes lysosomal turnover of lipids as well as proteins. The amelioration of lipid accumulation in TgCRND8 by removing cystatin B inhibition on lysosomal proteases suggests that enhancing lysosomal proteolysis improves the overall environment of the lysosome and its clearance functions, which may be possibly relevant to a broader range of lysosomal disorders beyond Alzheimer’s disease. PMID:25270989

Mild Lipid Stress Induces Profound Loss of MC4R Protein Abundance and Function

PubMed Central

Cragle, Faith K.

2014-01-01

Food intake is controlled at the central level by the melanocortin pathway in which the agonist α-MSH binds to melanocortin 4 receptor (MC4R), a Gs-coupled G protein-coupled receptor expressed by neurons in the paraventricular nuclei of the hypothalamus, which signals to reduce appetite. Consumption of a high-fat diet induces hypothalamic accumulation of palmitate, endoplasmic reticulum (ER) stress, apoptosis, and unresponsiveness to prolonged treatment with MC4R agonists. Here we have modeled effects of lipid stress on MC4R by using mHypoE-42 immortalized hypothalamic neurons expressing endogenous MC4R and Neuro2A cells expressing a tagged MC4R reporter, HA-MC4R-GFP. In the hypothalamic neurons, exposure to elevated palmitate in the physiological range induced splicing of X-box binding protein 1, but it did not activate C/EBP-homologous protein or induce increased levels of cleaved caspase-3, indicating mild ER stress. Such mild ER stress coexisted with a minimal loss of MC4R mRNA and yet a profound loss of cAMP signaling in response to incubation with the agonist. These findings were mirrored in the Neuro2A cells expressing HA-MC4R-GFP, in which protein abundance of the tagged receptor was decreased, whereas the activity per receptor number was maintained. The loss of cAMP signaling in response to α-MSH by elevated palmitate was corrected by treatment with a chemical chaperone, 4-phenylbutyrate in both mHypoE-42 hypothalamic neurons and in Neuro2A cells in which protein abundance of HA-MC4R-GFP was increased. The data indicate that posttranscriptional decrease of MC4R protein contribute to lower the response to α-MSH in hypothalamic neurons exposed to even a mild level of lipid stress and that a chemical chaperone corrects such a defect. PMID:24506538

The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia.

PubMed

Fruchart, Jean-Charles; Sacks, Frank; Hermans, Michel P; Assmann, Gerd; Brown, W Virgil; Ceska, Richard; Chapman, M John; Dodson, Paul M; Fioretto, Paola; Ginsberg, Henry N; Kadowaki, Takashi; Lablanche, Jean-Marc; Marx, Nikolaus; Plutzky, Jorge; Reiner, Zeljko; Rosenson, Robert S; Staels, Bart; Stock, Jane K; Sy, Rody; Wanner, Christoph; Zambon, Alberto; Zimmet, Paul

2008-11-17

Despite achieving targets for low-density lipoprotein (LDL) cholesterol, blood pressure, and glycemia in accordance with current standards of care, patients with dyslipidemia remain at high residual risk of vascular events. Atherogenic dyslipidemia, characterized by elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol, often with elevated apolipoprotein B and non-HDL cholesterol, is common in patients with established cardiovascular disease (CVD), type 2 diabetes mellitus, or metabolic syndrome and contributes to both macrovascular and microvascular residual risk. However, atherogenic dyslipidemia is largely underdiagnosed and undertreated in clinical practice. The Residual Risk Reduction Initiative (R3i) was established to address this highly relevant clinical issue. The aims of this position paper are (1) to highlight evidence that atherogenic dyslipidemia is associated with residual macrovascular and microvascular risk in patients at high risk for CVD, despite current standards of care for dyslipidemia and diabetes; and (2) to recommend therapeutic intervention for reducing this residual vascular risk supported by evidence and expert consensus. Lifestyle modification with nutrition and exercise is an important, effective, and underutilized first step in reducing residual vascular risk. Therapeutic intervention aimed at achievement of all lipid targets is also often required. Combination lipid-modifying therapy, with the addition of niacin, a fibrate, or omega-3 fatty acids to statin therapy, increases the probability of achieving all lipid goals. Outcomes studies are in progress to evaluate whether these combination treatment strategies translate to a clinical benefit greater than that achieved with statins alone. The R3i highlights the need to address with lifestyle and/or pharmacotherapy the high level of residual risk of CVD events and microvascular complications among patients with dyslipidemia receiving therapy for high levels of LDL cholesterol and for diabetes in accordance with current standards of care.

Palm oil and the heart: A review

PubMed Central

Odia, Osaretin J; Ofori, Sandra; Maduka, Omosivie

2015-01-01

Palm oil consumption and its effects on serum lipid levels and cardiovascular disease in humans is still a subject of debate. Advocacy groups with varying agenda fuel the controversy. This update intends to identify evidence-based evaluations of the influence of palm oil on serum lipid profile and cardiovascular disease. Furthermore, it suggests a direction for future research. The sources of information were based on a PubMed, Google Scholar, African Journal online and Medline search using key words including: palm oil, palmitic acid, saturated fatty acids and heart disease. Published animal and human experiments on the association of palm oil and its constituents on the serum lipid profile and cardiovascular disease were also explored for relevant information. These papers are reviewed and the available evidence is discussed. Most of the information in mainstream literature is targeted at consumers and food companies with a view to discourage the consumption of palm oil. The main argument against the use of palm oil as an edible oil is the fact that it contains palmitic acid, which is a saturated fatty acid and by extrapolation should give rise to elevated total cholesterol and low-density lipoprotein cholesterol levels. However, there are many scientific studies, both in animals and humans that clearly show that palm oil consumption does not give rise to elevated serum cholesterol levels and that palm oil is not atherogenic. Apart from palmitic acid, palm oil consists of oleic and linoleic acids which are monounsaturated and polyunsaturated respectively. Palm oil also consists of vitamins A and E, which are powerful antioxidants. Palm oil has been scientifically shown to protect the heart and blood vessels from plaques and ischemic injuries. Palm oil consumed as a dietary fat as a part of a healthy balanced diet does not have incremental risk for cardiovascular disease. Little or no additional benefit will be obtained by replacing it with other oils rich in mono or polyunsaturated fatty acids. PMID:25810814

A novel pathogenic variant of the LDLR gene in the Asian population and its clinical correlation with familial hypercholesterolemia.

PubMed

Chahil, J K; Lye, S H; Bagali, P G; Alex, L

2012-07-01

Familial hypercholesterolemia (FH) is a disease implicated with defects in either, Low density lipoprotein receptor gene (LDLR), Apolipoprotein B-100 gene (APOB), the Proprotein convertase subtilisin/kexin type 9 gene (PCSK9) or other related genes of the lipid metabolism pathway. The general characterization of heterozygous FH is by elevated low-density lipoprotein (LDL) cholesterol and early-onset cardiovascular diseases, while the more severe type, the homozygous FH results in extreme elevated levels of LDL cholesterol and usually death of an affected individual by early twenties. We present here a novel non-synonymous, missense mutation in exon 14 of the LDLR gene in two siblings of the Malay ethnicity discovered during an in-house genetic test. We postulate that their elevated cholesterol is due to this novel mutation and they are positive for homozygous FH. This is the first report of a C711Y mutation in patients with elevated cholesterol in Asia.

Development under elevated pCO2 conditions does not affect lipid utilization and protein content in early life-history stages of the purple sea urchin, Strongylocentrotus purpuratus.

PubMed

Matson, Paul G; Yu, Pauline C; Sewell, Mary A; Hofmann, Gretchen E

2012-12-01

Ocean acidification (OA) is expected to have a major impact on marine species, particularly during early life-history stages. These effects appear to be species-specific and may include reduced survival, altered morphology, and depressed metabolism. However, less information is available regarding the bioenergetics of development under elevated CO(2) conditions. We examined the biochemical and morphological responses of Strongylocentrotus purpuratus during early development under ecologically relevant levels of pCO(2) (365, 1030, and 1450 μatm) that may occur during intense upwelling events. The principal findings of this study were (1) lipid utilization rates and protein content in S. purpuratus did not vary with pCO(2); (2) larval growth was reduced at elevated pCO(2) despite similar rates of energy utilization; and (3) relationships between egg phospholipid content and larval length were found under control but not high pCO(2) conditions. These results suggest that this species may either prioritize endogenous energy toward development and physiological function at the expense of growth, or that reduced larval length may be strictly due to higher costs of growth under OA conditions. This study highlights the need to further expand our knowledge of the physiological mechanisms involved in OA response in order to better understand how present populations may respond to global environmental change.

Lifecycle of a Lipoprotein from a Biophysical Perspective

NASA Astrophysics Data System (ADS)

Rutledge, John C.; Huser, Thomas; Voss, John; Chan, James; Parikh, Atul

The goal of our project was to understand how lipids and lipoproteins interact with cell membranes. This chapter will present the five major areas in which we have focused our attention on understanding how lipids and lipoproteins interact with cell membranes (Fig. 11.1): (1) triglycerides and vascular injury, (2) single lipoprotein analysis, (3) apolipoprotein E (apoE) conformation changes in the postprandial state, (4) triglyceride-rich lipoproteins (TGRLs) and endothelial cell inflammation, and (5) TGRL lipolysis products and monocyte activation. For over a hundred years, Western civilization has questioned how the food we eat translates into disease, and specifically atherosclerotic cardiovascular disease. Although most information indicates that this basic pathophysiological process is mediated through consumption of excess saturated fats, much remains unknown. After humans eat a meal, there is an elevation of triglycerides in the blood in the postprandial state. In normal individuals, triglycerides can rise after a meal by 50 to 100%. This has been documented many times in the past, including a paper by Hyson et al, (1998) [1]. In that study, normal healthy individuals were given a 40%-fat meal. Plasma triglycerides, which were modestly elevated initially, rose about 60% higher three to four hours after ingestion of the meal. Subsequently plasma triglycerides fell to baseline levels six hours after the meal. Even in these healthy individuals, a significant elevation of triglycerides was noted after ingestion of a moder ately high-fat meal.

Perilipin overexpression in mice protects against diet-induced obesity

USDA-ARS?s Scientific Manuscript database

Perilipin A is the most abundant phosphoprotein on adipocyte lipid droplets and is essential for lipid storage and lipolysis. Perilipin null mice exhibit diminished adipose tissue, elevated basal lipolysis, reduced catecholamine-stimulated lipolysis, and increased insulin resistance. To understand t...

Correlation of serum biomarkers (TSA & LSA) and epithelial dysplasia in early diagnosis of oral precancer and oral cancer.

PubMed

Sawhney, Hemant; Kumar, C Anand

Oral cancer is currently the most frequent cause of cancer-related deaths, which is usually preceded by oral pre-cancerous lesions and conditions. Altered glycosylation of glycoconjugates, such as sialic acid, fucose, etc. are amongst the important molecular changes that accompany malignant transformation. The purpose of our study was to evaluate usefulness of serum Total Sialic Acid (TSA) and serum Lipid-Bound Sialic Acid (LSA) as markers of oral precancerous lesions and histopathologically correlating them with grades of epithelial dysplasia. Blood samples were collected from 50 patients with oral precancer (Leukoplakia & OSMF), 25 patients with untreated oral cancer and 25 healthy subjects. Serum sialic acid (total and lipid bound) levels were measured spectrophotometrically. Tissue samples from all the patients were evaluated for dysplasia. Serum levels of total and lipid bound sialic acid were significantly elevated in patients with oral precancer and cancer when compared with healthy subjects. Analysis of variance test documented that there is progressive rise in serum levels of sialic acid with the degree of dysplastic changes in oral precancer patients. We observed positive correlation between serum levels of the markers and the extent of malignant disease (TNM Clinical staging) as well as histopathological grades. The results suggested that serum levels of TSA and LSA progressively increases with grades of dysplasia in precancerous groups and cancer group, when compared with healthy controls. These glycoconjugates, especially LSA has the clinical utility in indicating a premalignant change.

Aging Increases Susceptibility to High Fat Diet-Induced Metabolic Syndrome in C57BL/6 Mice: Improvement in Glycemic and Lipid Profile after Antioxidant Therapy

PubMed Central

Nunes-Souza, Valéria; César-Gomes, Cheila Juliana; Da Fonseca, Lucas José Sá; Guedes, Glaucevane Da Silva; Smaniotto, Salete; Rabelo, Luíza Antas

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) has been considered a novel component of the metabolic syndrome (MetS), with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD-) induced MetS received apocynin and tempol 50 mg·kg−1/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD. PMID:27057272

Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake.

PubMed

Friday, K E; Drinkwater, B L; Bruemmer, B; Chesnut, C; Chait, A

1993-12-01

To determine the interactive effects of hormones, exercise, and diet on plasma lipids and lipoproteins, serum estrogen and progesterone levels, nutrient intake, and plasma lipid, lipoprotein, and apolipoprotein concentrations were measured in 24 hypoestrogenic amenorrheic and 44 eumenorrheic female athletes. When compared to eumenorrheic athletes, amenorrheic athletes had higher levels of plasma cholesterol (5.47 +/- 0.17 vs. 4.84 +/- 0.12 mmol/L, P = 0.003), triglyceride (0.75 +/- 0.06 vs. 0.61 +/- 0.03 mmol/L, P = 0.046), low-density lipoprotein (LDL; 3.16 +/- 0.15 vs. 2.81 +/- 0.09 mmol/L, P = 0.037), high-density lipoprotein (HDL; 1.95 +/- 0.07 vs. 1.73 +/- 0.05 mmol/L, P = 0.007), and HDL2 (0.84 +/- 0.06 vs. 0.68 +/- 0.04 mmol/L, P = 0.02) cholesterol. Plasma LDL/HDL cholesterol ratios, very low-density lipoprotein and HDL3 cholesterol, and apolipoprotein A-I and A-II levels were similar in the two groups. Amenorrheic athletes consumed less fat than eumenorrheic subjects (52 +/- 5 vs. 75 +/- 3 g/day, P = 0.02), but similar amounts of calories, cholesterol, protein, carbohydrate, and ethanol. HDL cholesterol levels in amenorrheic subjects correlated positively with the percent of dietary calories from fat (r = 0.42, n = 23, P = 0.045) but negatively with the percent from protein (r = -0.49, n = 23, P = 0.017). Thus, exercise-induced amenorrhea may adversely affect cardiovascular risk by increasing plasma LDL and total cholesterol. However, cardioprotective elevations in plasma HDL and HDL2 cholesterol may neutralize the risk of cardiovascular disease in amenorrheic athletes.

Epidermal growth factor receptor plays a role in the regulation of liver and plasma lipid levels in adult male mice.

PubMed

Scheving, Lawrence A; Zhang, Xiuqi; Garcia, Oscar A; Wang, Rebecca F; Stevenson, Mary C; Threadgill, David W; Russell, William E

2014-03-01

Dsk5 mice have a gain of function in the epidermal growth factor receptor (EGFR), caused by a point mutation in the kinase domain. We analyzed the effect of this mutation on liver size, histology, and composition. We found that the livers of 12-wk-old male Dsk5 heterozygotes (+/Dsk5) were 62% heavier compared with those of wild-type controls (+/+). The livers of the +/Dsk5 mice compared with +/+ mice had larger hepatocytes with prominent, polyploid nuclei and showed modestly increased cell proliferation indices in both hepatocytes and nonparenchymal cells. An analysis of total protein, DNA, and RNA (expressed relative to liver weight) revealed no differences between the mutant and wild-type mice. However, the livers of the +/Dsk5 mice had more cholesterol but less phospholipid and fatty acid. Circulating cholesterol levels were twice as high in adult male +/Dsk5 mice but not in postweaned young male or female mice. The elevated total plasma cholesterol resulted mainly from an increase in low-density lipoprotein (LDL). The +/Dsk5 adult mouse liver expressed markedly reduced protein levels of LDL receptor, no change in proprotein convertase subtilisin/kexin type 9, and a markedly increased fatty acid synthase and 3-hydroxy-3-methyl-glutaryl-CoA reductase. Increased expression of transcription factors associated with enhanced cholesterol synthesis was also observed. Together, these findings suggest that the EGFR may play a regulatory role in hepatocyte proliferation and lipid metabolism in adult male mice, explaining why elevated levels of EGF or EGF-like peptides have been positively correlated to increased cholesterol levels in human studies.

Dietary supplementation with arachidonic acid but not eicosapentaenoic or docosahexaenoic acids alter lipids metabolism in C57BL/6J mice.

PubMed

Magdeldin, Sameh; Elewa, Yaser; Ikeda, Takako; Ikei, Junko; Zhang, Ying; Xu, Bo; Nameta, Masaaki; Fujinaka, Hidehiko; Yoshida, Yutaka; Yaoita, Eishin; Yamamoto, Tadashi

2009-09-01

In order to investigate the effects of dietary supplementation rich in omega 3 and omega 6 fatty acids, we set up an experiment of twenty four C57BL/6J male mice segregated into 3 groups: normal diet (ND), omega 3 polyunsaturated fatty acid (n-3 PUFA,) and omega 6 (n-6 PUFA). At the end of the experiment that lasted for 1 month, food consumption of ND and n-3 PUFA were similar while it decreased in n-6 PUFA group. Total cholesterol, triglycerides, free fatty acids, and phospholipids profiles were increased in n-6 PUFA. LDL decreased in n-3 PUFA while increased in n-6 PUFA fed mice comparing to control group. On the other hand, there was no difference between treatments in HDL and glucose levels. Expression of leptin (ob) gene transcripts in epididymal fat were significantly elevated in n-6 PUFA mice compared to ND and n-3 PUFA groups while hypothalamic ob receptor A (obRa) mRNA did not changed in response to diet regimes. Transmission and scanning electron microscopy showed different degrees in fatty changes in the liver of both PUFA groups including lipid droplet infiltration and Ito cells with over accumulated lipids. In conclusion, under PUFA dietary supplementation, the hyperlipidemic status and elevated ob expression of n-6 PUFA but not n-3 PUFA fed mice suggests altered lipid metabolism between PUFA groups and/or different endocrine involvement. Moreover, the coincidently structural changes observed in liver of this group direct us to call for further studies to investigate the anti-obesity effect and safety of these PUFA under high supplementation condition.

Studies on lactoferricin-derived Escherichia coli membrane-active peptides reveal differences in the mechanism of N-acylated versus nonacylated peptides.

PubMed

Zweytick, Dagmar; Deutsch, Günter; Andrä, Jörg; Blondelle, Sylvie E; Vollmer, Ekkehard; Jerala, Roman; Lohner, Karl

2011-06-17

To improve the low antimicrobial activity of LF11, an 11-mer peptide derived from human lactoferricin, mutant sequences were designed based on the defined structure of LF11 in the lipidic environment. Thus, deletion of noncharged polar residues and strengthening of the hydrophobic N-terminal part upon adding a bulky hydrophobic amino acid or N-acylation resulted in enhanced antimicrobial activity against Escherichia coli, which correlated with the peptides' degree of perturbation of bacterial membrane mimics. Nonacylated and N-acylated peptides exhibited different effects at a molecular level. Nonacylated peptides induced segregation of peptide-enriched and peptide-poor lipid domains in negatively charged bilayers, although N-acylated peptides formed small heterogeneous domains resulting in a higher degree of packing defects. Additionally, only N-acylated peptides perturbed the lateral packing of neutral lipids and exhibited increased permeability of E. coli lipid vesicles. The latter did not correlate with the extent of improvement of the antimicrobial activity, which could be explained by the fact that elevated binding of N-acylated peptides to lipopolysaccharides of the outer membrane of gram-negative bacteria seems to counteract the elevated membrane permeabilization, reflected in the respective minimal inhibitory concentration for E. coli. The antimicrobial activity of the peptides correlated with an increase of membrane curvature stress and hence bilayer instability. Transmission electron microscopy revealed that only the N-acylated peptides induced tubular protrusions from the outer membrane, whereas all peptides caused detachment of the outer and inner membrane of E. coli bacteria. Viability tests demonstrated that these bacteria were dead before onset of visible cell lysis.

Studies on Lactoferricin-derived Escherichia coli Membrane-active Peptides Reveal Differences in the Mechanism of N-Acylated Versus Nonacylated Peptides*

PubMed Central

Zweytick, Dagmar; Deutsch, Günter; Andrä, Jörg; Blondelle, Sylvie E.; Vollmer, Ekkehard; Jerala, Roman; Lohner, Karl

2011-01-01

To improve the low antimicrobial activity of LF11, an 11-mer peptide derived from human lactoferricin, mutant sequences were designed based on the defined structure of LF11 in the lipidic environment. Thus, deletion of noncharged polar residues and strengthening of the hydrophobic N-terminal part upon adding a bulky hydrophobic amino acid or N-acylation resulted in enhanced antimicrobial activity against Escherichia coli, which correlated with the peptides' degree of perturbation of bacterial membrane mimics. Nonacylated and N-acylated peptides exhibited different effects at a molecular level. Nonacylated peptides induced segregation of peptide-enriched and peptide-poor lipid domains in negatively charged bilayers, although N-acylated peptides formed small heterogeneous domains resulting in a higher degree of packing defects. Additionally, only N-acylated peptides perturbed the lateral packing of neutral lipids and exhibited increased permeability of E. coli lipid vesicles. The latter did not correlate with the extent of improvement of the antimicrobial activity, which could be explained by the fact that elevated binding of N-acylated peptides to lipopolysaccharides of the outer membrane of Gram-negative bacteria seems to counteract the elevated membrane permeabilization, reflected in the respective minimal inhibitory concentration for E. coli. The antimicrobial activity of the peptides correlated with an increase of membrane curvature stress and hence bilayer instability. Transmission electron microscopy revealed that only the N-acylated peptides induced tubular protrusions from the outer membrane, whereas all peptides caused detachment of the outer and inner membrane of E. coli bacteria. Viability tests demonstrated that these bacteria were dead before onset of visible cell lysis. PMID:21515687

Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress

PubMed Central

Koncsos, Gábor; Varga, Zoltán V.; Boengler, Kerstin; Rohrbach, Susanne; Li, Ling; Schlüter, Klaus-Dieter; Schreckenberg, Rolf; Radovits, Tamás; Oláh, Attila; Mátyás, Csaba; Lux, Árpád; Al-Khrasani, Mahmoud; Komlódi, Tímea; Bukosza, Nóra; Máthé, Domokos; Deres, László; Barteková, Monika; Rajtík, Tomáš; Adameová, Adriana; Szigeti, Krisztián; Helyes, Zsuzsanna; Tretter, László; Pacher, Pál; Merkely, Béla; Schulz, Rainer; Ferdinandy, Péter

2016-01-01

Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4. High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phospholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto- and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca2+/calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria. PMID:27521417

A conserved SREBP-1/phosphatidylcholine feedback circuit regulates lipogenesis in metazoans.

PubMed

Walker, Amy K; Jacobs, René L; Watts, Jennifer L; Rottiers, Veerle; Jiang, Karen; Finnegan, Deirdre M; Shioda, Toshi; Hansen, Malene; Yang, Fajun; Niebergall, Lorissa J; Vance, Dennis E; Tzoneva, Monika; Hart, Anne C; Näär, Anders M

2011-11-11

Sterol regulatory element-binding proteins (SREBPs) activate genes involved in the synthesis and trafficking of cholesterol and other lipids and are critical for maintaining lipid homeostasis. Aberrant SREBP activity, however, can contribute to obesity, fatty liver disease, and insulin resistance, hallmarks of metabolic syndrome. Our studies identify a conserved regulatory circuit in which SREBP-1 controls genes in the one-carbon cycle, which produces the methyl donor S-adenosylmethionine (SAMe). Methylation is critical for the synthesis of phosphatidylcholine (PC), a major membrane component, and we find that blocking SAMe or PC synthesis in C. elegans, mouse liver, and human cells causes elevated SREBP-1-dependent transcription and lipid droplet accumulation. Distinct from negative regulation of SREBP-2 by cholesterol, our data suggest a feedback mechanism whereby maturation of nuclear, transcriptionally active SREBP-1 is controlled by levels of PC. Thus, nutritional or genetic conditions limiting SAMe or PC production may activate SREBP-1, contributing to human metabolic disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of seawater desalination and oil pollution on the lipid composition of blue mussels Mytilus edulis L. from the White Sea.

PubMed

Fokina, N N; Bakhmet, I N; Shklyarevich, G A; Nemova, N N

2014-12-01

A study on the effect oil pollution under normal and reduced salinity had on blue mussels Mytilus edulis L. from the White Sea in an aquarium-based experiment and in the natural habitat revealed a change in gill total lipids as a compensatory response. The cholesterol concentration and the cholesterol/phospholipids ratio in gills were found to reflect the impact of the environmental factors (oil pollution and desalination), and evidence adaptive changes in the cell membrane structure. An elevated content of storage lipids (chiefly triacylglycerols) in the mussels in the aquarium experiment indicates, first of all, the uptake and accumulation of oil products in gill cells under both normal and reduced seawater salinity, while high triacylglycerols level in gill littoral mussels from 'control' biotope in the Gulf of Kandalaksha is primarily associated with the mussel׳s pre-spawning period. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic cigarette smoking alters erythrocyte membrane lipid composition and properties in male human volunteers.

PubMed

Padmavathi, Pannuru; Reddy, Vaddi Damodara; Kavitha, Godugu; Paramahamsa, Maturu; Varadacharyulu, Nallanchakravarthula

2010-11-01

Cigarette smoking is a major lifestyle factor influencing the health of human beings. The present study investigates smoking induced alterations on the erythrocyte membrane lipid composition, fluidity and the role of nitric oxide. Thirty experimental and control subjects (age 35+/-8) were selected for the study. Experimental subjects smoke 12+/-2 cigarettes per day for 7-10 years. In smokers elevated nitrite/nitrate levels in plasma and red cell lysates were observed. Smokers showed increased hemolysis, erythrocyte membrane lipid peroxidation, protein carbonyls, C/P ratio (cholesterol and phospholipid ratio), anisotropic (gamma) value with decreased Na(+)/K(+)-ATPase activity and sulfhydryl groups. Alterations in smokers erythrocyte membrane individual phospholipids were also evident from the study. Red cell lysate nitric oxide positively correlated with C/P ratio (r=0.565) and fluorescent anisotropic (gamma) value (r=0.386) in smokers. Smoking induced generation of reactive oxygen/nitrogen species might have altered erythrocyte membrane physico-chemical properties. Copyright 2010 Elsevier Inc. All rights reserved.

Naturally occurring menopause in cynomolgus monkeys: changes in hormone, lipid, and carbohydrate measures with hormonal status.

PubMed

Kavanagh, Kylie; Koudy Williams, J; Wagner, Janice D

2005-08-01

Naturally occurring post-menopausal (PM) female cynomolgus monkeys (Macaca fascicularis) were identified. Their sex hormone profile was characterized and compared with younger pre-menopausal females before and after ovariectomy (OVX). PM females had lower estrogens and increased follicle-stimulating hormone (FSH) concentrations. Two PM females had diabetes mellitus and elevated androgens (androstenodione and dihydroepiandrosterone sulfate). Non-diabetic PM females were given parenteral E(2) which normalized FSH, and caused improvements in body weight, plasma lipids and lipoprotein cholesterol. Androgens remained lower with E(2) treatment. OVX induced comparable increases in FSH seen with the PM monkeys, however they had lower body weights, and had higher estrone and androstenodione concentrations. Natural menopause occurs in cynomolgus monkeys and hormone changes with OVX are similar however, differences in sex hormones that can relate to body mass and age may be important. E(2) treatment restored estrogen levels and induced improvements in the lipid profile of PM females.

LipiD-QuanT: a novel method to quantify lipid accumulation in live cells[S

PubMed Central

Varinli, Hilal; Osmond-McLeod, Megan J.; Molloy, Peter L.; Vallotton, Pascal

2015-01-01

Lipid droplets (LDs) are the main storage organelles for triglycerides. Elucidation of lipid accumulation mechanisms and metabolism are essential to understand obesity and associated diseases. Adipogenesis has been well studied in murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell lines. However, most techniques for measuring LD accumulation are either not quantitative or can be destructive to samples. Here, we describe a novel, label-free LD quantification technique (LipiD-QuanT) to monitor lipid dynamics based on automated image analysis of phase contrast microscopy images acquired during in vitro human adipogenesis. We have applied LipiD-QuanT to measure LD accumulation during differentiation of SGBS cells. We demonstrate that LipiD-QuanT is a robust, nondestructive, time- and cost-effective method compared with other triglyceride accumulation assays based on enzymatic digest or lipophilic staining. Further, we applied LipiD-QuanT to measure the effect of four potential pro- or antiobesogenic substances: DHA, rosiglitazone, elevated levels of D-glucose, and zinc oxide nanoparticles. Our results revealed that 2 µmol/l rosiglitazone treatment during adipogenesis reduced lipid production and caused a negative shift in LD diameter size distribution, but the other treatments showed no effect under the conditions used here. PMID:26330056

Micronutrients-fortified rapeseed oil improves hepatic lipid accumulation and oxidative stress in rats fed a high-fat diet

PubMed Central

2013-01-01

Intake of high-fat diet is associated with increased fatty livers. Hepatic lipid accumulation and oxidative stress are key pathophysiological mechanisms in this disease. Micronutrients polyphenols, tocopherols and phytosterols in rapeseed exert potential benefit to hepatoprotection, but most of these micronutrients are removed by the traditional refining process. The purpose of the present study was to determine whether rapeseed oil fortified with these micronutrients can decrease hepatic lipid accumulation and oxidative stress induced by high-fat diet. Sprague–Dawley rats received rodent diet contained 20% fat whose source was refined rapeseed oil (RRO) or fortified RRO with low, middle and high quantities of these micronutrients for 10 weeks. Intake of RRO caused a remarkable hepatic steatosis. Micronutrients supplementation was effective in reducing steatosis as well as total triglyceride and total cholesterol contents in liver. These micronutrients also significantly increased hepatic antioxidant defense capacities, as evaluated by the significant elevation in the activities of SOD and GPx as well as the level of GSH, and the significant decline in lipid peroxidation. These findings suggest that rapeseed oil fortified with micronutrients polyphenols, tocopherols and phytosterols may contribute to prevent fatty livers such as nonalcoholic fatty liver disease by ameliorating hepatic lipid accumulation and oxidative stress. PMID:23510587

Trivalent Chromium Supplementation Ameliorates Oleic Acid-Induced Hepatic Steatosis in Mice.

PubMed

Wang, Song; Wang, Jian; Liu, Yajing; Li, Hui; Wang, Qiao; Huang, Zhiwei; Liu, Wenbin; Shi, Ping

2018-05-24

Trivalent chromium [Cr(III)] is recognized as an essential trace element for human health, whereas its effect on hepatic lipid metabolism has not yet been fully understood. This study aimed to investigate the beneficial effects and potential mechanisms of Cr(III) on hepatic steatosis in an oleic acid (OA) induced mice model. Mice were fed with high OA for 12 weeks to induce lipid accumulation, and co-administrated with Cr(III) supplementation. Indexes of liver lipid accumulation, associated lipid genes expression, fatty acids (FAs) profile and inflammatory cytokines were analyzed. The data showed that Cr(III) supplementation could attenuate disease progress of hepatic steatosis and protect liver from high OA. After Cr(III) supplementation, elevated body weight and liver injury in steatosis mice were reversed, excessive lipid accumulation and FAs were also reduced. The up-regulation of cluster of differentiation 36 (CD36) and diacylglycerol acyltransferase 2 (DGAT2) following steatosis induction were inhibited by Cr(III). Cr(III) reduced the content of pro-inflammatory cytokines (IL-1β and TNF-α, IL-12) and restored the level of anti-inflammatory cytokine (IL-10) to the control values. Our results suggest that Cr(III) supplementation is a novel strategy for alleviating OA-induced hepatic steatosis.

Lipid mobilising factors specifically associated with cancer cachexia.

PubMed Central

Beck, S. A.; Tisdale, M. J.

1991-01-01

Both urine and plasma from mice and humans with cancer cachexia have been shown to contain higher levels of lipid mobilising activity than normal controls, even after acute starvation. There was no significant increase in the urinary lipid mobilising activity of either mice or humans after acute starvation, suggesting that the material in the cachectic situation was probably not due to an elevation of hormones normally associated with the catabolic state in starvation. Further characterisation of the lipid mobilising activity in the urine of cachectic mice using Sephadex G50 exclusion chromatography showed four distinct peaks of activity of apparent molecular weights of greater than 20, 3, 1.5 and less than 0.7 kDa. No comparable peaks of activity were found in the urine of a non tumour-bearing mouse. The high molecular weight activity was probably formed by aggregation of low molecular weight material, since treatment with 0.5 M NaCl caused dissociation to material with a broad spectrum of molecular weights between 3 and 0.7 kDa. Lipolytic species of similar molecular weights were also found in the urine of cachectic cancer patients, but not in normal urine even after 24 h starvation. The lipid mobilising species may be responsible for catabolism of host adipose tissue in the cachectic state. PMID:2069843

Phosphoinositide 5-phosphatase Fig 4p is required for both acute rise and subsequent fall in stress-induced phosphatidylinositol 3,5-bisphosphate levels.

PubMed

Duex, Jason E; Nau, Johnathan J; Kauffman, Emily J; Weisman, Lois S

2006-04-01

Phosphoinositide lipids regulate complex events via the recruitment of proteins to a specialized region of the membrane at a specific time. Precise control of both the synthesis and turnover of phosphoinositide lipids is integral to membrane trafficking, signal transduction, and cytoskeletal rearrangements. Little is known about the acute regulation of the levels of these signaling lipids. When Saccharomyces cerevisiae cells are treated with hyperosmotic medium the levels of phosphatidylinositol 3,5-bisphosphate (PI3,5P(2)) increase 20-fold. Here we show that this 20-fold increase is rapid and occurs within 5 min. Surprisingly, these elevated levels are transient. Fifteen minutes following hyperosmotic shock they decrease at a rapid rate, even though the cells remain in hyperosmotic medium. In parallel with the rapid increase in the levels of PI3,5P(2), vacuole volume decreases rapidly. Furthermore, concomitant with a return to basal levels of PI3,5P(2) vacuole volume is restored. We show that Fig 4p, consistent with its proposed role as a PI3,5P(2) 5-phosphatase, is required in vivo for this rapid return to basal levels of PI3,5P(2). Surprisingly, we find that Fig 4p is also required for the hyperosmotic shock-induced increase in PI3,5P(2) levels. These findings demonstrate that following hyperosmotic shock, large, transient changes occur in the levels of PI3,5P(2) and further suggest that Fig 4p is important in regulating both the acute rise and subsequent fall in PI3,5P(2) levels.

Sulfite Oxidase Activity Is Essential for Normal Sulfur, Nitrogen and Carbon Metabolism in Tomato Leaves

PubMed Central

Brychkova, Galina; Yarmolinsky, Dmitry; Batushansky, Albert; Grishkevich, Vladislav; Khozin-Goldberg, Inna; Fait, Aaron; Amir, Rachel; Fluhr, Robert; Sagi, Moshe

2015-01-01

Plant sulfite oxidase [SO; E.C.1.8.3.1] has been shown to be a key player in protecting plants against exogenous toxic sulfite. Recently we showed that SO activity is essential to cope with rising dark-induced endogenous sulfite levels in tomato plants (Lycopersicon esculentum/Solanum lycopersicum Mill. cv. Rheinlands Ruhm). Here we uncover the ramifications of SO impairment on carbon, nitrogen and sulfur (S) metabolites. Current analysis of the wild-type and SO-impaired plants revealed that under controlled conditions, the imbalanced sulfite level resulting from SO impairment conferred a metabolic shift towards elevated reduced S-compounds, namely sulfide, S-amino acids (S-AA), Co-A and acetyl-CoA, followed by non-S-AA, nitrogen and carbon metabolite enhancement, including polar lipids. Exposing plants to dark-induced carbon starvation resulted in a higher degradation of S-compounds, total AA, carbohydrates, polar lipids and total RNA in the mutant plants. Significantly, a failure to balance the carbon backbones was evident in the mutants, indicated by an increase in tricarboxylic acid cycle (TCA) cycle intermediates, whereas a decrease was shown in stressed wild-type plants. These results indicate that the role of SO is not limited to a rescue reaction under elevated sulfite, but SO is a key player in maintaining optimal carbon, nitrogen and sulfur metabolism in tomato plants. PMID:27135342

Association of apolipoprotein E gene polymorphism with ischemic stroke involving large-vessel disease and its relation to serum lipid levels.

PubMed

Saidi, Sarra; Slamia, Lamia B; Ammou, Sofyan B; Mahjoub, Touhami; Almawi, Wassim Y

2007-01-01

A relationship between apolipoprotein E (Apo E) genotype and stroke was previously suggested, but with inconsistent results. We investigated the relationships among serum lipid levels, Apo E alleles and genotypes, and stroke risk factors in 216 stroke patients and 282 age- and sex-matched controls. Fasting blood samples were collected for total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride level determination and for genomic DNA extraction. Apo was genotyped by polymerase chain reaction-restriction fragment length polymorphism (Cfo I) analysis. Increasing levels of total cholesterol, LDL-C, HDL-C, and triglycerides were associated with elevated stroke risk and was more pronounced in Apo E4-carrying subjects than in E3- and/or E2-carrying subjects. Apo 3 was significantly lower (0.546 vs 0.736; P < .001), whereas Apo 4 was higher in the stroke patients (0.370 vs 0.181; P < .001); Apo 2 was present at low but comparable frequencies. The prevalence of E3/E3 was lower and that of E4-containing phenotypes (E3/E4 and homozygous E4/E4) was higher in the stroke patients. The prevalence of the E4-containing phenotypes were significantly higher in ischemic versus hemorrhagic (P < .001) and in small-vessel versus large-vessel stroke cases (P < .001), and was associated with increased need for statin drugs (P = .040). Logistic regression models, after adjusting for potentially confounding variables including lipid profile, age, and sex, showed an significant association of apo 4 genotype with risk of stroke (P = .033). Our findings indicate that Apo 4 is an independent risk factor associated with an altered lipid profile in this study population.

How does predation affect the bioaccumulation of hydrophobic organic compounds in aquatic organisms?

PubMed

Xia, Xinghui; Li, Husheng; Yang, Zhifeng; Zhang, Xiaotian; Wang, Haotian

2015-04-21

It is well-known that the body burden of hydrophobic organic compounds (HOCs) increases with the trophic level of aquatic organisms. However, the mechanism of HOC biomagnification is not fully understood. To fill this gap, this study investigated the effect of predation on the bioaccumulation of polycyclic aromatic hydrocarbons (PAHs), one type of HOC, in low-to-high aquatic trophic levels under constant freely dissolved PAH concentrations (1, 5, or 10 μg L(-1)) maintained by passive dosing systems. The tested PAHs included phenanthrene, anthracene, fluoranthene, and pyrene. The test organisms included zebrafish, which prey on Daphnia magna, and cichlids, which prey on zebrafish. The results revealed that for both zebrafish and cichlids, predation elevated the uptake and elimination rates of PAHs. The increase of uptake rate constant ranged from 20.8% to 39.4% in zebrafish with the amount of predation of 5 daphnids per fish per day, and the PAH uptake rate constant increased with the amount of predation. However, predation did not change the final bioaccumulation equilibrium; the equilibrium concentrations of PAHs in fish only depended on the freely dissolved concentration in water. Furthermore, the lipid-normalized water-based bioaccumulation factor of each PAH was constant for fish at different trophic levels. These findings infer that the final bioaccumulation equilibrium of PAHs is related to a partition between water and lipids in aquatic organisms, and predation between trophic levels does not change bioaccumulation equilibrium but bioaccumulation kinetics at stable freely dissolved PAH concentrations. This study suggests that if HOCs have not reached bioaccumulation equilibrium, biomagnification occurs due to enhanced uptake rates caused by predation in addition to higher lipid contents in higher trophic organisms. Otherwise, it is only due to the higher lipid contents in higher trophic organisms.

Experimental increase in baseline corticosterone level reduces oxidative damage and enhances innate immune response

PubMed Central

Pătraș, Laura; Pap, Péter L.; Vincze, Orsolya; Mureșan, Cosmin; Németh, József; Lendvai, Ádám Z.

2018-01-01

Glucocorticoid (GC) hormones are significant regulators of homeostasis. The physiological effects of GCs critically depend on the time of exposure (short vs. long) as well as on their circulating levels (baseline vs. stress-induced). Previous experiments, in which chronic and high elevation of GC levels was induced, indicate that GCs impair both the activity of the immune system and the oxidative balance. Nonetheless, our knowledge on how mildly elevated GC levels, a situation much more common in nature, might influence homeostasis is limited. Therefore, we studied whether an increase in GC level within the baseline range suppresses or enhances condition (body mass, hematocrit and coccidian infestation) and physiological state (humoral innate immune system activity and oxidative balance). We implanted captive house sparrows Passer domesticus with either 60 days release corticosterone (CORT) or control pellets. CORT-treated birds had elevated baseline CORT levels one week after the implantation, but following this CORT returned to its pre-treatment level and the experimental groups had similar CORT levels one and two months following the implantation. The mass of tail feathers grown during the initial phase of treatment was smaller in treated than in control birds. CORT implantation had a transient negative effect on body mass and hematocrit, but both of these traits resumed the pre-treatment values by one month post-treatment. CORT treatment lowered oxidative damage to lipids (malondialdehyde) and enhanced constitutive innate immunity at one week and one month post-implantation. Our findings suggest that a relatively short-term (i.e. few days) elevation of baseline CORT might have a positive and stimulatory effect on animal physiology. PMID:29432437

Palmitic Acid Reduces Circulating Bone Formation Markers in Obese Animals and Impairs Osteoblast Activity via C16-Ceramide Accumulation.

PubMed

Alsahli, Ahmad; Kiefhaber, Kathryn; Gold, Tziporah; Muluke, Munira; Jiang, Hongfeng; Cremers, Serge; Schulze-Späte, Ulrike

2016-05-01

Obesity and impaired lipid metabolism increase circulating and local fatty acid (FA) levels. Our previous studies showed that a high high-saturated -fat diet induced greater bone loss in mice than a high high-unsaturated-fat diet due to increased osteoclast numbers and activity. The impact of elevated FA levels on osteoblasts is not yet clear. We induced obesity in 4 week old male mice using a palmitic acid (PA)- or oleic acid (OA)-enriched high fat high-fat diet (HFD) (20 % of calories from FA), and compared them to mice on a normal (R) caloric diet (10 % of calories from FA). We collected serum to determine FA and bone metabolism marker levels. Primary osteoblasts were isolated; cultured in PA, OA, or control (C) medium; and assessed for mineralization activity, gene expression, and ceramide levels. Obese animals in the PA and OA groups had significantly lower serum levels of bone formation markers P1NP and OC compared to normal weight animals (*p < 0.001), with the lowest marker levels in animals on an PA-enriched HFD (*p < 0.001). Accordingly, elevated levels of PA significantly reduced osteoblast mineralization activity in vitro (*p < 0.05). Elevated PA intake significantly increased C16 ceramide accumulation. This accumulation was preventable through inhibition of SPT2 (serine palmitoyl transferase 2) using myriocin. Elevated levels of PA reduce osteoblast function in vitro and bone formation markers in vivo. Our findings suggest that saturated PA can compromise bone health by affecting osteoblasts, and identify a potential mechanism through which obesity promotes bone loss.

Association of polymorphisms of genes involved in lipid metabolism with blood pressure and lipid values in mexican hypertensive individuals.

PubMed

Ríos-González, Blanca Estela; Ibarra-Cortés, Bertha; Ramírez-López, Guadalupe; Sánchez-Corona, José; Magaña-Torres, María Teresa

2014-01-01

Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP). We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in Mexican hypertensive (HT) patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC -514T, and MTTP -493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17-2.93; P = 0.001) under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients.

Association of Polymorphisms of Genes Involved in Lipid Metabolism with Blood Pressure and Lipid Values in Mexican Hypertensive Individuals

PubMed Central

Ríos-González, Blanca Estela; Ibarra-Cortés, Bertha; Ramírez-López, Guadalupe; Sánchez-Corona, José; Magaña-Torres, María Teresa

2014-01-01

Hypertension and dyslipidemia exhibit an important clinical relationship because an increase in blood lipids yields an increase in blood pressure (BP). We analyzed the associations of seven polymorphisms of genes involved in lipid metabolism (APOA5 rs3135506, APOB rs1042031, FABP2 rs1799883, LDLR rs5925, LIPC rs1800588, LPL rs328, and MTTP rs1800591) with blood pressure and lipid values in Mexican hypertensive (HT) patients. A total of 160 HT patients and 160 normotensive individuals were included. Genotyping was performed through PCR-RFLP, PCR-AIRS, and sequencing. The results showed significant associations in the HT group and HT subgroups classified as normolipemic and hyperlipemic. The alleles FABP2 p.55T, LIPC −514T, and MTTP −493T were associated with elevated systolic BP. Five alleles were associated with lipids. LPL p.474X and FABP2 p.55T were associated with decreased total cholesterol and LDL-C, respectively; APOA5 p.19W with increased HDL-C; APOA5 p.19W and FABP2 p.55T with increased triglycerides; and APOB p.4181K and LDLR c.1959T with decreased triglycerides. The APOB p.E4181K polymorphism increases the risk for HT (OR = 1.85, 95% CI: 1.17–2.93; P = 0.001) under the dominant model. These findings indicate that polymorphisms of lipid metabolism genes modify systolic BP and lipid levels and may be important in the development of essential hypertension and dyslipidemia in Mexican HT patients. PMID:25587205

Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for membrane phospholipid synthesis.

PubMed

Han, Gil-Soo; Carman, George M

2017-08-11

The PAH1 -encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae , exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of membrane phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1 -encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major phospholipids via the CDP-diacylglycerol pathway. The lack of PAP in the pah1 Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1 Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1 Δ mutant is induced through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UAS INO mutation suppressed pah1 Δ effects on lipid synthesis, nuclear/endoplasmic reticulum membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1 -encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1 Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for membrane phospholipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Genetic Predisposition to Increased Blood Cholesterol and Triglyceride Lipid Levels and Risk of Alzheimer Disease: A Mendelian Randomization Analysis

PubMed Central

Proitsi, Petroula; Lupton, Michelle K.; Velayudhan, Latha; Newhouse, Stephen; Fogh, Isabella; Tsolaki, Magda; Daniilidou, Makrina; Pritchard, Megan; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Williams, Julie; Stewart, Robert; Sham, Pak; Lovestone, Simon; Powell, John F.

2014-01-01

Background Although altered lipid metabolism has been extensively implicated in the pathogenesis of Alzheimer disease (AD) through cell biological, epidemiological, and genetic studies, the molecular mechanisms linking cholesterol and AD pathology are still not well understood and contradictory results have been reported. We have used a Mendelian randomization approach to dissect the causal nature of the association between circulating lipid levels and late onset AD (LOAD) and test the hypothesis that genetically raised lipid levels increase the risk of LOAD. Methods and Findings We included 3,914 patients with LOAD, 1,675 older individuals without LOAD, and 4,989 individuals from the general population from six genome wide studies drawn from a white population (total n = 10,578). We constructed weighted genotype risk scores (GRSs) for four blood lipid phenotypes (high-density lipoprotein cholesterol [HDL-c], low-density lipoprotein cholesterol [LDL-c], triglycerides, and total cholesterol) using well-established SNPs in 157 loci for blood lipids reported by Willer and colleagues (2013). Both full GRSs using all SNPs associated with each trait at p<5×10−8 and trait specific scores using SNPs associated exclusively with each trait at p<5×10−8 were developed. We used logistic regression to investigate whether the GRSs were associated with LOAD in each study and results were combined together by meta-analysis. We found no association between any of the full GRSs and LOAD (meta-analysis results: odds ratio [OR] = 1.005, 95% CI 0.82–1.24, p = 0.962 per 1 unit increase in HDL-c; OR = 0.901, 95% CI 0.65–1.25, p = 0.530 per 1 unit increase in LDL-c; OR = 1.104, 95% CI 0.89–1.37, p = 0.362 per 1 unit increase in triglycerides; and OR = 0.954, 95% CI 0.76–1.21, p = 0.688 per 1 unit increase in total cholesterol). Results for the trait specific scores were similar; however, the trait specific scores explained much smaller phenotypic variance. Conclusions Genetic predisposition to increased blood cholesterol and triglyceride lipid levels is not associated with elevated LOAD risk. The observed epidemiological associations between abnormal lipid levels and LOAD risk could therefore be attributed to the result of biological pleiotropy or could be secondary to LOAD. Limitations of this study include the small proportion of lipid variance explained by the GRS, biases in case-control ascertainment, and the limitations implicit to Mendelian randomization studies. Future studies should focus on larger LOAD datasets with longitudinal sampled peripheral lipid measures and other markers of lipid metabolism, which have been shown to be altered in LOAD. Please see later in the article for the Editors' Summary PMID:25226301

Hepatoprotective and antioxidant activity of Phaseolus trilobus, Ait on bile duct ligation induced liver fibrosis in rats.

PubMed

Fursule, R A; Patil, S D

2010-06-16

Phaseolus trilobus Ait (Fabaceae) is extensively used by tribal people of Nandurbar district (Maharashtra, India) in the treatment of Jaundice and other liver disorders. of the present study was to assess the medicinal claim of Phaseolus trilobus as hepatoprotective and antioxidant. The hepatoprotective activity of methanol and aqueous extract of Phaseolus trilobus was evaluated by bile duct ligation induced liver fibrosis and antioxidant activity was evaluated using in vitro and in vivo antioxidant models viz anti-lipid peroxidation assay, super oxide radical scavenging assay and glutathione estimation in liver. Liver function tests were carried out to detect hepatoprotective activity, which was further supported by histopathological examination. Methanol and aqueous extracts of Phaseolus trilobus reduced elevated level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and hydroxyproline significantly (p<0.01) in bile duct ligated Wistar rats, proving hepatoprotective activity comparable with Silymarin. Both the extracts were found to reduce the elevated levels of serum thiobarbituric acid reactive substance (TBARS) and elevate superoxide scavenging radical activity proving antioxidant activity comparable with ascorbic acid. The reduced level of glutathione was found to be elevated in liver proving antioxidant activity comparable with Silymarin. Phaseolus trilobus posses hepatoprotective property and is effective in oxidative stress induced cholestatic hepatic injury. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Anti-oxidative protection against iron overload-induced liver damage in mice by Cajanus cajan (L.) Millsp. leaf extract.

PubMed

Sarkar, Rhitajit; Hazra, Bibhabasu; Mandal, Nripendranath

2013-02-01

In view of the contribution of iron deposition in the oxidative pathologic process of liver disease, the potential of 70% methanolic extract of C. cajan leaf (CLME) towards antioxidative protection against iron-overload-induced liver damage in mice has been investigated. DPPH radical scavenging and protection of Fenton reaction induced DNA damage was conducted in vitro. Post oral administration of CLME to iron overloaded mice, the levels of antioxidant and serum enzymes, hepatic iron, serum ferritin, lipid peroxidation, and protein carbonyl and hydroxyproline contents were measured, in comparison to deferasirox treated mice. Oral treatment of the plant extract effectively lowered the elevated levels of liver iron, lipid peroxidation, protein carbonyl and hydroxyproline. There was notable increment in the dropped levels of hepatic antioxidants. The dosage of the plant extract not only made the levels of serum enzymes approach normal value, but also counteracted the overwhelmed serum ferritin level. The in vitro studies indicated potential antioxidant activity of CLME. The histopathological observations also substantiated the ameliorative function of the plant extract. Accordingly, it is suggested that Cajanus cajan leaf can be a useful herbal remedy to suppress oxidative damage caused by iron overload.

Expression of holo and apo forms of spinach acyl carrier protein-I in leaves of transgenic tobacco plants.

PubMed Central

Post-Beittenmiller, M A; Schmid, K M; Ohlrogge, J B

1989-01-01

Acyl carrier protein (ACP) is a chloroplast-localized cofactor of fatty acid synthesis, desaturation, and acyl transfer. We have transformed tobacco with a chimeric gene consisting of the tobacco ribulose-1,5-bisphosphate carboxylase promoter and transit peptide and the sequence encoding the mature spinach ACP-I. Spinach ACP-I was expressed in the transformed plants at levels twofold to threefold higher than the endogenous tobacco ACPs as determined by protein immunoblots and assays of ACP in leaf extracts. In addition to these elevated levels of the holo form, there were high levels of apoACP-I, a form lacking the 4'-phosphopantetheine prosthetic group and not previously detected in vivo. The mature forms of both apoACP-I and holoACP-I were located in the chloroplasts, indicating that the transit peptide was cleaved and that attachment of the prosthetic group was not required for uptake into the plastid. There were also significant levels of spinach acyl-ACP-I, demonstrating that spinach ACP-I participated in tobacco fatty acid metabolism. Lipid analyses of the transformed plants indicated that the increased ACP levels caused no significant alterations in leaf lipid biosynthesis. PMID:2535529

Phosphorylation of WRINKLED1 by KIN10 Results in Its Proteasomal Degradation, Providing a Link between Energy Homeostasis and Lipid Biosynthesis[OPEN

PubMed Central

Liu, Hui

2017-01-01

WRINKLED1 (WRI1), a member of the APETALA2 (AP2) class of transcription factors, positively regulates glycolysis and lipid biosynthesis in Arabidopsis thaliana. Here, we identify mechanistic links between KIN10, the major SUCROSE NON-FERMENTATION1-RELATED KINASE1 involved in sugar/energy homeostasis, and the posttranslational regulation of WRI1. Transient expression of WRI1 with OLEOSIN1 in Nicotiana benthamiana stimulates triacylglycerol accumulation, but their coexpression with KIN10 abrogates this effect by inducing proteasomal degradation of WRI1. While WRI1 lacks canonical KIN10 target sequences, we demonstrated direct KIN10-dependent phosphorylation of WRI1 using purified Escherichia coli-expressed components. The resulting phosphorylated WRI1 was more rapidly degraded than native WRI1 in cell-free degradation assays. WRI1 phosphorylation was localized to two variants of the canonical KIN10 recognition sequence, one in each of its two AP2 DNA binding domains. Conversion of the phosphorylation sites at Thr-70 and Ser-166 to Ala resulted in a loss of KIN10-dependent phosphorylation, and when coexpressed with KIN10 the WRI1 double mutant accumulated to 2- to 3-fold higher levels than native WRI1. KIN10-dependent degradation of WRI1 provides a homeostatic mechanism that favors lipid biosynthesis when intracellular sugar levels are elevated and KIN10 is inhibited; conversely, glycolysis and lipid biosynthesis are curtailed as sugar levels decrease and KIN10 regains activity. PMID:28314829

Dioxins and Nonortho PCBs in Breast Milk of Vietnamese Mothers Living in the Largest Hot Spot of Dioxin Contamination.

PubMed

Nghi, Tran Ngoc; Nishijo, Muneko; Manh, Ho Dung; Tai, Pham The; Van Luong, Hoang; Anh, Tran Hai; Thao, Pham Ngoc; Trung, Nguyen Viet; Waseda, Tomoo; Nakagawa, Hideaki; Kido, Teruhiko; Nishijo, Hisao

2015-05-05

Bien Hoa Air Base is the largest dioxin contamination hot spot in Vietnam. In 2012, we recruited 216 mothers who were living in 10 communities around Bien Hoa Air Base and had delivered newborns at a prefecture hospital, and we investigated recent exposure levels of dioxins and nonortho PCBs in their breast milk. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (2,3,7,8-tetraCDD) was present at 2.6 pg/g lipid in primiparae and 2.2 pg/g lipid in multiparae. Among multiparae and total subjects, significant high prevalence of 2,3,7,8-tetraCDD≥5 pg/g lipid and 2,3,7,8-tetraCDD contribution≥40% were observed in mothers living in the five communities closest to Bien Hoa Air Base. The TEQ for nonortho PCBs was 1.6 pg-TEQ/g lipid for primiparae, and this was even lower than that in the unsprayed area. The length of residency was a strong factor to increase dioxins, including 2,3,7,8-tetraCDD. Residency in the five communities with the highest exposure was a specific risk factor for increased 2,3,7,8-tetraCDD in breast milk. Food intake might contribute partly to the increased levels of dioxin congeners other than 2,3,7,8-tetraCDD in breast milk. These results suggest that Bien Hoa Air Base has led to elevated 2,3,7,8-tetraCDD levels in breast milk of mothers in nearby areas even in the recent years.

The novel selective PPARα modulator (SPPARMα) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis.

PubMed

Hennuyer, Nathalie; Duplan, Isabelle; Paquet, Charlotte; Vanhoutte, Jonathan; Woitrain, Eloise; Touche, Véronique; Colin, Sophie; Vallez, Emmanuelle; Lestavel, Sophie; Lefebvre, Philippe; Staels, Bart

2016-06-01

Atherosclerosis is characterized by lipid accumulation and chronic inflammation in the arterial wall. Elevated levels of apolipoprotein (apo) B-containing lipoproteins are a risk factor for cardiovascular disease (CVD). By contrast, plasma levels of functional high-density lipoprotein (HDL) and apoA-I are protective against CVD by enhancing reverse cholesterol transport (RCT). Activation of peroxisome proliferator-activated receptor-α (PPARα), a ligand-activated transcription factor, controls lipid metabolism, cellular cholesterol trafficking in macrophages and influences inflammation. To study whether pharmacological activation of PPARα with a novel highly potent and selective PPARα modulator, pemafibrate, improves lipid metabolism, macrophage cholesterol efflux, inflammation and consequently atherosclerosis development in vitro and in vivo using human apolipoprotein E2 Knock-In (apoE2KI) and human apoA-I transgenic (hapoA-I tg) mice. Pemafibrate treatment decreases apoB secretion in chylomicrons by polarized Caco-2/TC7 intestinal epithelium cells and reduces triglyceride levels in apoE2KI mice. Pemafibrate treatment of hapoA-I tg mice increases plasma HDL cholesterol, apoA-I and stimulates RCT to feces. In primary human macrophages, pemafibrate promotes macrophage cholesterol efflux to HDL and exerts anti-inflammatory activities. Pemafibrate also reduces markers of inflammation and macrophages in the aortic crosses as well as aortic atherosclerotic lesion burden in western diet-fed apoE2KI mice. These results demonstrate that the novel selective PPARα modulator pemafibrate exerts beneficial effects on lipid metabolism, RCT and inflammation resulting in anti-atherogenic properties. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Phosphorylation of WRINKLED1 by KIN10 Results in its Proteasomal Degradation, Providing a Link Between Energy Homeostasis and Lipid Biosynthesis

DOE PAGES

Zhai, Zhiyang; Liu, Hui; Shanklin, John

2017-03-17

WRINKLED1 (WRI1), a member of the APETALA2 (AP2) class of transcription factors, positively regulates glycolysis and lipid biosynthesis in Arabidopsis thaliana. Here we identify mechanistic links between KIN10, the major SUCROSE NON-FERMENTATION-1 (SNF1)-RELATED KINASE 1 (SnRK1) involved in sugar/energy homeostasis and the posttranslational regulation of WRI1. Transient expression of WRI1 with OLEOSIN1 (OLE1) in Nicotiana benthamiana stimulates triacylglycerol (TAG) accumulation, but their coexpression with KIN10 abrogates this effect by inducing proteasomal degradation of WRI1. While WRI1 lacks canonical KIN10 target sequences, we demonstrated direct KIN10-dependent phosphorylation of WRI1 using purified E. coli-expressed components. The resulting phosphorylated WRI1 was more rapidlymore » degraded than native WRI1 in cell-free degradation assays. WRI1 phosphorylation was localized to two variants of the canonical KIN10 recognition sequence, one in each of its two AP2 DNA-binding domains. Conversion of the phosphorylation sites at T70 and S166 to Ala resulted in a loss of KIN10-dependent phosphorylation, and when coexpressed with KIN10 the WRI1 double mutant accumulated to 2-3 fold higher levels than native WRI1. In conclusion, KIN10-dependent degradation of WRI1 provides a homeostatic mechanism that favors lipid biosynthesis when intracellular sugar levels are elevated and KIN10 is inhibited; conversely, glycolysis and lipid biosynthesis are curtailed as sugar levels decrease and KIN10 regains activity.« less

Phosphorylation of WRINKLED1 by KIN10 Results in its Proteasomal Degradation, Providing a Link Between Energy Homeostasis and Lipid Biosynthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhai, Zhiyang; Liu, Hui; Shanklin, John

WRINKLED1 (WRI1), a member of the APETALA2 (AP2) class of transcription factors, positively regulates glycolysis and lipid biosynthesis in Arabidopsis thaliana. Here we identify mechanistic links between KIN10, the major SUCROSE NON-FERMENTATION-1 (SNF1)-RELATED KINASE 1 (SnRK1) involved in sugar/energy homeostasis and the posttranslational regulation of WRI1. Transient expression of WRI1 with OLEOSIN1 (OLE1) in Nicotiana benthamiana stimulates triacylglycerol (TAG) accumulation, but their coexpression with KIN10 abrogates this effect by inducing proteasomal degradation of WRI1. While WRI1 lacks canonical KIN10 target sequences, we demonstrated direct KIN10-dependent phosphorylation of WRI1 using purified E. coli-expressed components. The resulting phosphorylated WRI1 was more rapidlymore » degraded than native WRI1 in cell-free degradation assays. WRI1 phosphorylation was localized to two variants of the canonical KIN10 recognition sequence, one in each of its two AP2 DNA-binding domains. Conversion of the phosphorylation sites at T70 and S166 to Ala resulted in a loss of KIN10-dependent phosphorylation, and when coexpressed with KIN10 the WRI1 double mutant accumulated to 2-3 fold higher levels than native WRI1. In conclusion, KIN10-dependent degradation of WRI1 provides a homeostatic mechanism that favors lipid biosynthesis when intracellular sugar levels are elevated and KIN10 is inhibited; conversely, glycolysis and lipid biosynthesis are curtailed as sugar levels decrease and KIN10 regains activity.« less

Toxic alveolitis after inhalation of a water repellent.

PubMed

Epping, Guido; Van Baarlen, Joop; Van Der Valk, Paul D L P M

2011-12-01

Inhalation of fluorocarbon polymers can cause pulmonary toxicity. Although multiple cases of lung injury have been reported, cellular characterization of the associated alveolitis occurring acutely after inhalation is limited. We report the case of a previously healthy woman who presented at our Emergency Department with an acute pneumonitis following inhalation of a fluorocarbon polymer-based rain-proofing spray. Bronchoalveolar lavage (BAL) performed shortly after the presentation showed an elevated total cell count, with a high proportion of neutrophils (58%) and eosinophils (9%). In addition, a lipid stain (Oil-Red-O-stain) showed a high level of lipid laden macrophages, a marker that could reflect a direct toxic effect of the spray on alveolar cells. The patient made a full recovery after four days of in-hospital observation with supportive care.

Managing statin-induced muscle toxicity in a lipid clinic.

PubMed

Blaier, O; Lishner, M; Elis, A

2011-06-01

Muscle toxicity is the most significant adverse effect related to statins. The aim of the study was to analyse the clinical course and achievement of LDL-C target levels in patients with statin-induced muscle toxicity. All patients who were referred to the lipid clinic because of statin-induced muscle toxicity, or developed it during follow-up, or did not reach LDL-C target levels because of its previous occurrence, and attended the clinic for at least three follow-up visits, were eligible. Files were reviewed for demographic and clinical parameters, coronary heart disease risk level, the severity of muscle injury, the type of statin and dose that caused the adverse effects, the clinical approach and outcome, and whether the LDL-C target level was achieved. The study group consisted of 54 patients. Twenty-three (43%) patients complained of myalgia, 23 (43%) had asymptomatic serum creatine kinase (CK) level elevation, five (9%) had myopathy and three (5%) had rhabdomyolysis. Fifty of the patients (93%) continued statin therapy and 43 (80%) achieved the LDL-C target level. We show that for the majority of patients with statin-induced muscle toxicity, statin therapy can be safely and effectively continued. In cases of asymptomatic CK levels <3-5 upper limit of normal (ULN), statin treatment should not be interrupted. When CK levels >3-5 ULN or when various symptomatic muscle adverse reactions are present, statins rechallenge, after a recovery period, should be individualized either by a low dose of a potent statin or by a less potent statin. An additional lipid medication is advised if the target levels are not achieved. © 2011 Blackwell Publishing Ltd.

Chromium dinicocysteinate supplementation can lower blood glucose, CRP, MCP-1, ICAM-1, creatinine, apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 in livers of zucker diabetic fatty rats.

PubMed

Jain, Sushil K; Croad, Jennifer L; Velusamy, Thirunavukkarasu; Rains, Justin L; Bull, Rebeca

2010-09-01

Chromium and cysteine supplementation can improve glucose metabolism in animal studies. This study examined the hypothesis that a cysteinate complex of chromium is significantly beneficial than either of them in lowering blood glucose and vascular inflammation markers in Zucker diabetic fatty (ZDF) rats. Starting at the age of 6 wk, ZDF rats were supplemented orally (daily gavages for 8 more weeks) with saline-placebo (D) or chromium (400 microg Cr/Kg body weight) as chromium dinicocysteinate (CDNC), chromium dinicotinate (CDN) or chromium picolinate (CP) or equimolar L-cysteine (LC, img/Kg body weight), and fed Purina 5008 diet for 8 wk. ZDF rats of 6 wk age before any supplementations and onset of diabetes were considered as baseline. D rats showed elevated levels of fasting blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and oxidative stress (lipid peroxidation) and lower adiponectin and vitamin C, when compared with baseline rats. In comparison to D group, CDNC group had significantly lower blood glucose, HbA(1), CRP, MCP-1, ICAM-1 and lipid peroxidation and increased vitamin C and adiponectin levels. CDN, CP or LC showed significantly less or no effect on these biomarkers. Only CDNC lowered blood creatinine levels in comparison to D. While CDN and CP had no effect, activation of NFkappaB, Akt and glucose transporter-2 levels were decreased, insulin receptor substrate 1 (IRS-1) activation increased in livers of CDNC-rats. CDNC effect on glycemia, NFkappaB, Akt and IRS-1 in liver was significantly greater compared with LC. Blood chromium levels did not differ between Cr-groups. Exogenous vitamin C supplementation significantly inhibited MCP-1 secretion in U937 monocytes cultured in high-glucose-medium. CDNC is a potent hypoglycemic compound with anti-inflammatory activity apparently mediated by elevated blood vitamin C and adiponectin and inhibition of NFkappaB, Akt, and Glut-2 and increased IRS-1 activation in livers of type 2 diabetic rats.

Elevated Serum Fibroblast Growth Factor 21 Levels in Patients With Hyperthyroidism.

PubMed

Xiao, Fangsen; Lin, Mingzhu; Huang, Peiying; Zeng, Jinyang; Zeng, Xin; Zhang, Huijie; Li, Xiaoying; Yang, Shuyu; Li, Zhibin; Li, Xuejun

2015-10-01

Recent evidence from animal studies indicates that fibroblast growth factor 21 (FGF21), an endocrine hormone that regulates glucose, lipid metabolism, and energy homeostasis, is regulated by T3. However, the role of FGF21 in hyperthyroid patients is unknown. The objective was to study serum FGF21 levels in hyperthyroid patients and the association of serum FGF21 levels with hyperthyroidism. This was a case-control study. A total of 119 hyperthyroid patients and 108 healthy subjects were recruited. Of them, 41 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism was obtained. Serum FGF21 levels were determined using the ELISA method. Serum FGF21 levels were significantly elevated in hyperthyroid patients as compared with normal subjects [median 290.67 (interquartile range, 156.60-502.33) vs 228.10 (169.85.25-320.10) pg/mL; P < .001]. After thionamide treatment, serum FGF21 levels in hyperthyroid patients declined markedly from 249.10 (139.10-444.00) to 106.90 (38.70-196.15) pg/mL (P < .001). Logistic regression revealed that FGF21, basal metabolic rate, low-density lipoprotein cholesterol, and alanine transaminase were significantly associated with hyperthyroidism. With adjustment for potential confounders, serum FGF21 remained independently associated with hyperthyroidism, with an adjusted odds ratio of 3.123 (95% confidence interval, 1.306-7.468) (P = .010). Serum FGF21 levels were elevated in patients with hyperthyroidism and declined after thionamide treatment. And serum FGF21 level was independently associated with hyperthyroidism.

Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation

PubMed Central

Dias, Irundika H.K.; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M.; Polidori, Maria C.; Lip, Gregory Y.H.; Griffiths, Helen R.

2014-01-01

Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4 μg oxLDL and 25 µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells. PMID:25048970

Dietary Zinc Deficiency Exaggerates Ethanol-Induced Liver Injury in Mice: Involvement of Intrahepatic and Extrahepatic Factors

PubMed Central

Sun, Xinguo; Song, Zhenyuan; McClain, Craig J.; Zhou, Zhanxiang

2013-01-01

Clinical studies have demonstrated that alcoholics have a lower dietary zinc intake compared to health controls. The present study was undertaken to determine the interaction between dietary zinc deficiency and ethanol consumption in the pathogenesis of alcoholic liver disease. C57BL/6N mice were subjected to 8-week feeding of 4 experimental liquid diets: (1) zinc adequate diet, (2) zinc adequate diet plus ethanol, (3) zinc deficient diet, and (4) zinc deficient diet plus ethanol. Ethanol exposure with adequate dietary zinc resulted in liver damage as indicated by elevated plasma alanine aminotransferase level and increased hepatic lipid accumulation and inflammatory cell infiltration. Dietary zinc deficiency alone increased hepatic lipid contents, but did not induce hepatic inflammation. Dietary zinc deficiency showed synergistic effects on ethanol-induced liver damage. Dietary zinc deficiency exaggerated ethanol effects on hepatic genes related to lipid metabolism and inflammatory response. Dietary zinc deficiency worsened ethanol-induced imbalance between hepatic pro-oxidant and antioxidant enzymes and hepatic expression of cell death receptors. Dietary zinc deficiency exaggerated ethanol-induced reduction of plasma leptin, although it did not affect ethanol-induced reduction of white adipose tissue mass. Dietary zinc deficiency also deteriorated ethanol-induced gut permeability increase and plasma endotoxin elevation. These results demonstrate, for the first time, that dietary zinc deficiency is a risk factor in alcoholic liver disease, and multiple intrahepatic and extrahepatic factors may mediate the detrimental effects of zinc deficiency. PMID:24155903

Prognostic value, clinical effectiveness and cost-effectiveness of high sensitivity C-reactive protein as a marker in primary prevention of major cardiac events.

PubMed

Schnell-Inderst, Petra; Schwarzer, Ruth; Göhler, Alexander; Grandi, Norma; Grabein, Kristin; Stollenwerk, Björn; Klauß, Volker; Wasem, Jürgen; Siebert, Uwe

2009-05-12

In a substantial portion of patients (= 25%) with coronary heart disease (CHD), a myocardial infarction or sudden cardiac death without prior symptoms is the first manifestation of disease. The use of new risk predictors for CHD such as the high-sensitivity C-reactive Protein (hs-CRP) in addition to established risk factors could improve prediction of CHD. As a consequence of the altered risk assessment, modified preventive actions could reduce the number of cardiac death and non-fatal myocardial infarction. Does the additional information gained through the measurement of hs-CRP in asymptomatic patients lead to a clinically relevant improvement in risk prediction as compared to risk prediction based on traditional risk factors and is this cost-effective? A literature search of the electronic databases of the German Institute of Medical Documentation and Information (DIMDI) was conducted. Selection, data extraction, assessment of the study-quality and synthesis of information was conducted according to the methods of evidence-based medicine. Eight publications about predictive value, one publication on the clinical efficacy and three health-economic evaluations were included. In the seven study populations of the prediction studies, elevated CRP-levels were almost always associated with a higher risk of cardiovascular events and non-fatal myocardial infarctions or cardiac death and severe cardiovascular events. The effect estimates (odds ratio (OR), relative risk (RR), hazard ratio (HR)), once adjusted for traditional risk factors, demonstrated a moderate, independent association between hs-CRP and cardiac and cardiovascular events that fell in the range of 0.7 to 2.47. In six of the seven studies, a moderate increase in the area under the curve (AUC) could be detected by adding hs-CRP as a predictor to regression models in addition to established risk factors though in three cases this was not statistically significant. The difference [in the AUC] between the models with and without hs-CRP fell between 0.00 and 0.023 with a median of 0.003. A decision-analytic modeling study reported a gain in life-expectancy for those using statin therapy for populations with elevated hs-CRP levels and normal lipid levels as compared to statin therapy for those with elevated lipid levels (approximately 6.6 months gain in life-expectancy for 58 year olds). Two decision-analytic models (three publications) on cost-effectiveness reported incremental cost-effectiveness ratios between Euro 8,700 and 50,000 per life year gained for the German context and between 52,000 and 708,000 for the US context. The empirical input data for the model is highly uncertain. No sufficient evidence is available to support the notion that hs-CRP-values should be measured during the global risk assessment for CAD or cardiovascular disease in addition to the traditional risk factors. The additional measurement of the hs-CRP-level increases the incremental predictive value of the risk prediction. It has not yet been clarified whether this increase is clinically relevant resulting in reduction of cardiovascular morbidity and mortality. For people with medium cardiovascular risk (5 to 20% in ten years) additional measurement of hs-CRP seems most likely to be clinical relevant to support the decision as to whether or not additional statin therapy should be initiated for primary prevention. Statin therapy can reduce the occurrence of cardiovascular events for asymptomatic individuals with normal lipid and elevated hs-CRP levels. However, this is not enough to provide evidence for a clinical benefit of hs-CRP-screening. The cost-effectiveness of general hs-CRP-screening as well as screening among only those with normal lipid levels remains unknown at present.

The predictive effect of inflammatory markers and lipid accumulation product index on clinical symptoms associated with polycystic ovary syndrome in nonobese adolescents and younger aged women.

PubMed

Tola, Esra Nur; Yalcin, Serenat Eris; Dugan, Nadiye

2017-07-01

The aim of our study is to analyse the inflammatory markers and lipid accumulation product (LAP) index in nonobese adolescents and younger aged women with polycystic ovary syndrome (PCOS) compared with age and body mass index (BMI)-matched healthy controls and to determine whether the investigated parameters are potential markers for the etiopathogenesis of PCOS. We also aim to determine whether these inflammatory markers are predictive for developing some clinical implications, such as cardiovascular disease (CVD) and insulin resistance (IR), associated with PCOS. A total of 34 adolescents and younger aged females with PCOS, and 33 age and BMI-matched healthy controls were recruited for our study. All participants were nonobese (BMI<25). Neopterin (NEO), C-reactive protein (CRP) levels and complete blood parameters were assessed. LAP index and homeostasis model assessment of IR (HOMA-IR) were calculated; anthropometric, clinical and biochemical parameters were also recorded. Serum NEO, CRP levels and LAP index were significantly increased in nonobese adolescents and younger aged females with PCOS compared to healthy controls. We could not found any predictive effect of investigated inflammatory markers and LAP index on CVD risk among PCOS patients after adjustment for abdominal obesity. We also found a positive predictive effect of WBC and a negative predictive effect of lymphocytes on IR in PCOS patients after adjustment for abdominal obesity. We did not find any predictor effect of NEO on IR, but it was a positive predictive marker for an elevated HOMA-IR index. Elevated NEO, CRP levels and LAP index could have potential roles in the etiopathogenesis of PCOS in nonobese adolescents and younger aged females,NEO could be a predictive marker for elevated HOMA-IR index, and WBC and lymphocytes could be predictive for the development of IR among nonobese adolescents and younger aged females with PCOS. Copyright © 2017 Elsevier B.V. All rights reserved.

Elevated plasma free fatty acids increase cardiovascular risk by inducing plasma biomarkers of endothelial activation, myeloperoxidase and PAI-1 in healthy subjects.

PubMed

Mathew, Manoj; Tay, Eric; Cusi, Kenneth

2010-02-16

CVD in obesity and T2DM are associated with endothelial activation, elevated plasma vascular inflammation markers and a prothrombotic state. We examined the contribution of FFA to these abnormalities following a 48-hour physiological increase in plasma FFA to levels of obesity and diabetes in a group of healthy subjects. 40 non-diabetic subjects (age = 38 +/- 3 yr, BMI = 28 +/- 1 kg/m2, FPG = 95 +/- 1 mg/dl, HbA1c = 5.3 +/- 0.1%) were admitted twice and received a 48-hour infusion of normal saline or low-dose lipid. Plasma was drawn for intracellular (ICAM-1) and vascular (VCAM-1) adhesion molecules-1, E-selectin (sE-S), myeloperoxidase (MPO) and total plasminogen inhibitor-1 (tPAI-1). Insulin sensitivity was measured by a hyperglycemic clamp (M/I). Lipid infusion increased plasma FFA to levels observed in obesity and T2DM and reduced insulin sensitivity by 27% (p = 0.01). Elevated plasma FFA increased plasma markers of endothelial activation ICAM-1 (138 +/- 10 vs. 186 +/- 25 ng/ml), VCAM-1 (1066 +/- 67 vs. 1204 +/- 65 ng/ml) and sE-S (20 +/- 1 vs. 24 +/- 1 ng/ml) between 13-35% and by > or = 2-fold plasma levels of myeloperoxidase (7.5 +/- 0.9 to 15 +/- 25 ng/ml), an inflammatory marker of future CVD, and tPAI-1 (9.7 +/- 0.6 to 22.5 +/- 1.5 ng/ml), an indicator of a prothrombotic state (all p < or = 0.01). The FFA-induced increase was independent from the degree of adiposity, being of similar magnitude in lean, overweight and obese subjects. An increase in plasma FFA within the physiological range observed in obesity and T2DM induces markers of endothelial activation, vascular inflammation and thrombosis in healthy subjects. This suggests that even transient (48-hour) and modest increases in plasma FFA may initiate early vascular abnormalities that promote atherosclerosis and CVD.

Alpha2delta-1 in SF1+ Neurons of the Ventromedial Hypothalamus Is an Essential Regulator of Glucose and Lipid Homeostasis.

PubMed

Felsted, Jennifer A; Chien, Cheng-Hao; Wang, Dongqing; Panessiti, Micaella; Ameroso, Dominique; Greenberg, Andrew; Feng, Guoping; Kong, Dong; Rios, Maribel

2017-12-05

The central mechanisms controlling glucose and lipid homeostasis are inadequately understood. We show that α2δ-1 is an essential regulator of glucose and lipid balance, acting in steroidogenic factor-1 (SF1) neurons of the ventromedial hypothalamus (VMH). These effects are body weight independent and involve regulation of SF1 + neuronal activity and sympathetic output to metabolic tissues. Accordingly, mice with α2δ-1 deletion in SF1 neurons exhibit glucose intolerance, altered lipolysis, and decreased cholesterol content in adipose tissue despite normal energy balance regulation. Profound reductions in the firing rate of SF1 neurons, decreased sympathetic output, and elevated circulating levels of serotonin are associated with these alterations. Normal calcium currents but reduced excitatory postsynaptic currents in mutant SF1 neurons implicate α2δ-1 in the promotion of excitatory synaptogenesis separate from its canonical role as a calcium channel subunit. Collectively, these findings identify an essential mechanism that regulates VMH neuronal activity and glycemic and lipid control and may be a target for tackling metabolic disease. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Glutathione S-transferases as antioxidant defence agents confer pyrethroid resistance in Nilaparvata lugens.

PubMed Central

Vontas, J G; Small, G J; Hemingway, J

2001-01-01

Selection of a laboratory colony of the brown planthopper Nilaparvata lugens with the pyrethroids permethrin and lambda-cyhalothrin increased its resistance to both insecticides. Biochemical analysis and synergistic studies with metabolic inhibitors indicated that elevated glutathione S-transferases (GSTs) with a predominant peroxidase activity conferred resistance to both pyrethroids, whereas esterases conferred part of the resistance to permethrin. Purified esterases hydrolysed permethrin at a slow rate, but incubation of either pyrethroid or their primary metabolites with partially purified GSTs had no effect on the metabolic profile. Although GSTs were sensitive to inhibition by both pyrethroids, they did not serve as binding proteins, as previously hypothesized [Grant and Matsumura (1988) Insect Biochem. 18, 615-622]. We demonstrate that pyrethroids, in addition to their neurotoxic effect, induce oxidative stress and lipid peroxidation in insects. Pyrethroid exposure induced lipid peroxides, protein oxidation and depleted reduced glutathione. Elevated GSTs in the resistant strains attenuated the pyrethroid-induced lipid peroxidation and reduced mortality, whereas their in vivo inhibition eliminated their protective role. We therefore hypothesize that the main role of elevated GSTs in conferring resistance in N. lugens is through protecting tissues from oxidative damage. Our study extends the GSTs' range of efficacy to pyrethroid insecticides and possibly explains the role of elevated GSTs in other pyrethroid-resistant insects. PMID:11415437

Hepatocellular integrity after parenteral nutrition: comparison of a fish-oil-containing lipid emulsion with an olive-soybean oil-based lipid emulsion.

PubMed

Piper, Swen N; Schade, Ingo; Beschmann, Ralf B; Maleck, Wolfgang H; Boldt, Joachim; Röhm, Kerstin D

2009-12-01

Parenteral nutrition including lipids might be associated with liver disease. The cause leading to parenteral nutrition-related liver dysfunction remains largely unknown but is likely to be multifactorial. The study was performed to assess the effects of a lipid emulsion based on soybean oil, medium-chain triglycerides, olive and fish oil (SMOFlipid20%) compared with a lipid emulsion based on olive and soybean oil on hepatic integrity. In a prospective, randomized, double-blinded trial, 44 postoperative patients with an indication for parenteral nutrition were allocated to one of two regimens: group A (n = 22) received SMOFlipid, group B (n = 22) a lipid emulsion based on olive and soybean oil for 5 days. Aspartate aminotransferase, alanin-aminotransferase, and serum alpha-glutathion S-transferase were measured before the start of parenteral nutrition (d0), at day 2 (d2), and day 5 (d5) after the start of parenteral nutrition. The significance level was defined at a P value of less than 0.05. There was no significant difference at d0, but at d2 and d5, significantly lower aspartate aminotransferase (d2: group A: 27 +/- 13 vs. group B: 47 +/- 36 U l(-1); d5: A: 31 +/- 14 vs. B: 56 +/- 45 U l(-1)), alanin-aminotransferase (d2: A: 20 +/- 12 vs. B: 42 +/- 39 U l(-1); d5: A: 26 +/- 15 vs. B: 49 +/- 44 U l(-1)), and alpha-glutathion S-transferase levels (d2: A: 5 +/- 6 vs. B: 17 +/- 21 U l(-1); d5: A: 6 +/- 7 vs. B: 24 +/- 27 microg l(-1)) were found in soybean oil, medium-chain triglycerides, olive and fish oil group compared with the control group. Hepatic integrity was well retained with the administration of SMOFlipid whereas in patients receiving a lipid emulsion based on olive and soybean oil liver enzymes were elevated indicating a lower liver tolerability.

DHEA-induced modulation of renal gluconeogenesis, insulin sensitivity and plasma lipid profile in the control- and dexamethasone-treated rabbits. Metabolic studies.

PubMed

Kiersztan, Anna; Nagalski, Andrzej; Nalepa, Paweł; Tempes, Aleksandra; Trojan, Nina; Usarek, Michał; Jagielski, Adam K

2016-02-01

In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several dexP-evoked effects, it seems likely, that its supplementation might be beneficial to patients treated with glucocorticoids. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Plasma Lipids and Betaine Are Related in an Acute Coronary Syndrome Cohort

PubMed Central

Lever, Michael; George, Peter M.; Atkinson, Wendy; Molyneux, Sarah L.; Elmslie, Jane L.; Slow, Sandy; Richards, A. Mark; Chambers, Stephen T.

2011-01-01

Background Low plasma betaine has been associated with unfavorable plasma lipid profiles and cardiovascular risk. In some studies raised plasma betaine after supplementation is associated with elevations in plasma lipids. We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these. Methodology Fasting plasma samples were collected from 531 subjects (and urine samples from 415) 4 months after hospitalization for an acute coronary syndrome episode. In this cross-sectional study, plasma betaine and dimethylglycine concentrations and urine excretions were compared with plasma lipid concentrations. Subgroup comparisons were made for gender, with and without diabetes mellitus, and for drug treatment. Principal Findings Plasma betaine negatively correlated with triglyceride (Spearman's rs = −0.22, p<0.0001) and non-high-density lipoprotein cholesterol (rs = −0.27, p<0.0001). Plasma betaine was a predictor of BMI (p<0.05) and plasma non-high-density lipoprotein cholesterol and triglyceride (p<0.001) independently of gender, age and the presence of diabetes. Using data grouped by plasma betaine decile, increasing plasma betaine was linearly related to decreases in BMI (p = 0.008) and plasma non-HDL cholesterol (p = 0.002). In a non-linear relationship betaine was negatively associated with elevated plasma triglycerides (p = 0.004) only for plasma betaine >45 µmol/L. Subjects taking statins had higher plasma betaine concentrations (p<0.001). Subjects treated with a fibrate had lower plasma betaine (p = 0.003) possibly caused by elevated urine betaine loss (p<0.001). The ratio of coenzyme Q to non-high-density lipoprotein cholesterol was higher in subjects with higher plasma betaine, and in subjects taking a statin. Conclusion Low plasma betaine concentrations correlated with an unfavourable lipid profile. Betaine deficiency may be common in the study population. Controlled clinical trials of betaine supplementation should be conducted in appropriate populations to determine whether correction affects cardiovascular risk. PMID:21747945

Cholesterol, Triglycerides, and the Five-Factor Model of Personality

PubMed Central

Sutin, Angelina R.; Terracciano, Antonio; Deiana, Barbara; Uda, Manuela; Schlessinger, David; Lakatta, Edward G.; Costa, Paul T.

2010-01-01

Unhealthy lipid levels are among the leading controllable risk factors for coronary heart disease. To identify the psychological factors associated with dyslipidemia, this study investigates the personality correlates of cholesterol (total, LDL, and HDL) and triglycerides. A community-based sample (N=5,532) from Sardinia, Italy, had their cholesterol and triglyceride levels assessed and completed a comprehensive personality questionnaire, the NEO-PI-R. All analyses controlled for age, sex, BMI, smoking, drinking, hypertension, and diabetes. Low Conscientiousness and traits related to impulsivity were associated with lower HDL cholesterol and higher triglycerides. Compared to the lowest 10%, those who scored in top 10% on Impulsivity had a 2.5 times greater risk of exceeding the clinical threshold for elevated triglycerides (OR=2.51, CI=1.56–4.07). In addition, sex moderated the association between trait depression (a component of Neuroticism) and HDL cholesterol, such that trait depression was associated with lower levels of HDL cholesterol in women but not men. When considering the connection between personality and health, unhealthy lipid profiles may be one intermediate biomarker between personality and morbidity and mortality. PMID:20109519

Synergistic protective role of mirazid (Commiphora molmol) and ascorbic acid against tilmicosin-induced cardiotoxicity in mice.

PubMed

Abdel-Daim, Mohamed M; Ghazy, Emad W; Fayez, Mostafa

2015-01-01

Tilmicosin (TIL) is a long-acting macrolide antibiotic approved for the treatment of cattle with Bovine Respiratory Disease. However, overdose of TIL has been reported to induce cardiotoxicity. The purpose of our experiment was to evaluate the protective effects of Commiphora molmol (mirazid (MRZ); myrrh) and (or) ascorbic acid (AA) against TIL-induced cardiotoxicity in mice. MRZ and AA were orally administered using stomach gavage, either alone or in combination for 5 consecutive days, followed with a single TIL overdose. TIL overdose induced a significant increase in serum levels of cardiac damage biomarkers (AST, LDH, CK, CK-MB, and cTnT), as well as cardiac lipid peroxidation, but cardiac levels of antioxidant biomarkers (GSH, SOD, CAT, and TAC) were decreased. Both MRZ and AA tended to normalize the elevated serum levels of cardiac injury biomarkers. Furthermore, MRZ and AA reduced TIL-induced lipid peroxidation and oxidative stress parameters. MRZ and AA combined produced a synergistic cardioprotective effect. We conclude that myrrh and (or) vitamin C administration minimizes the toxic effects of TIL through their free-radical-scavenging and potent antioxidant activities.

Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men.

PubMed

Riales, R; Albrink, M J

1981-12-01

Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

Additional Antiepileptic Mechanisms of Levetiracetam in Lithium-Pilocarpine Treated Rats

PubMed Central

Al-Shorbagy, Muhammad Y.; El Sayeh, Bahia M.; Abdallah, Dalaal M.

2013-01-01

Several studies have addressed the antiepileptic mechanisms of levetiracetam (LEV); however, its effect on catecholamines and the inflammatory mediators that play a role in epilepsy remain elusive. In the current work, lithium (Li) pretreated animals were administered LEV (500 mg/kg i.p) 30 min before the induction of convulsions by pilocarpine (PIL). Li-PIL-induced seizures were accompanied by increased levels of hippocampal prostaglandin (PG) E2, myeloperoxidase (MPO), tumor necrosis factor-α, and interleukin-10. Moreover, it markedly elevated hippocampal lipid peroxides and nitric oxide levels, while it inhibited the glutathione content. Li-PIL also reduced hippocampal noradrenaline, as well as dopamine contents. Pretreatment with LEV protected against Li-PIL-induced seizures, where it suppressed the severity and delayed the onset of seizures in Li-PIL treated rats. Moreover, LEV reduced PGE2 and MPO, yet it did not affect the level of both cytokines in the hippocampus. LEV also normalized hippocampal noradrenaline, dopamine, glutathione, lipid peroxides, and nitric oxide contents. In conclusion, alongside its antioxidant property, LEV anticonvulsive effect involves catecholamines restoration, as well as inhibition of PGE2, MPO, and nitric oxide. PMID:24098559

Caveolins/caveolae protect adipocytes from fatty acid-mediated lipotoxicity.

PubMed

Meshulam, Tova; Breen, Michael R; Liu, Libin; Parton, Robert G; Pilch, Paul F

2011-08-01

Mice and humans lacking functional caveolae are dyslipidemic and have reduced fat stores and smaller fat cells. To test the role of caveolins/caveolae in maintaining lipid stores and adipocyte integrity, we compared lipolysis in caveolin-1 (Cav1)-null fat cells to that in cells reconstituted for caveolae by caveolin-1 re-expression. We find that the Cav1-null cells have a modestly enhanced rate of lipolysis and reduced cellular integrity compared with reconstituted cells as determined by the release of lipid metabolites and lactic dehydrogenase, respectively, into the media. There are no apparent differences in the levels of lipolytic enzymes or hormonally stimulated phosphorylation events in the two cell lines. In addition, acute fasting, which dramatically raises circulating fatty acid levels in vivo, causes a significant upregulation of caveolar protein constituents. These results are consistent with the hypothesis that caveolae protect fat cells from the lipotoxic effects of elevated levels fatty acids, which are weak detergents at physiological pH, by virtue of the property of caveolae to form detergent-resistant membrane domains.

Caveolins/caveolae protect adipocytes from fatty acid-mediated lipotoxicity

PubMed Central

Meshulam, Tova; Breen, Michael R.; Liu, Libin; Parton, Robert G.; Pilch, Paul F.

2011-01-01

Mice and humans lacking functional caveolae are dyslipidemic and have reduced fat stores and smaller fat cells. To test the role of caveolins/caveolae in maintaining lipid stores and adipocyte integrity, we compared lipolysis in caveolin-1 (Cav1)-null fat cells to that in cells reconstituted for caveolae by caveolin-1 re-expression. We find that the Cav1-null cells have a modestly enhanced rate of lipolysis and reduced cellular integrity compared with reconstituted cells as determined by the release of lipid metabolites and lactic dehydrogenase, respectively, into the media. There are no apparent differences in the levels of lipolytic enzymes or hormonally stimulated phosphorylation events in the two cell lines. In addition, acute fasting, which dramatically raises circulating fatty acid levels in vivo, causes a significant upregulation of caveolar protein constituents. These results are consistent with the hypothesis that caveolae protect fat cells from the lipotoxic effects of elevated levels fatty acids, which are weak detergents at physiological pH, by virtue of the property of caveolae to form detergent-resistant membrane domains. PMID:21652731

Natural thermal adaptation increases heat shock protein levels and decreases oxidative stress.

PubMed

Oksala, Niku K J; Ekmekçi, F Güler; Ozsoy, Ergi; Kirankaya, Serife; Kokkola, Tarja; Emecen, Güzin; Lappalainen, Jani; Kaarniranta, Kai; Atalay, Mustafa

2014-01-01

Heat shock proteins (HSPs), originally identified as heat-inducible gene products, are a family of highly conserved proteins that respond to a wide variety of stress including oxidative stress. Although both acute and chronic oxidative stress have been well demonstrated to induce HSP responses, little evidence is available whether increased HSP levels provide enhanced protection against oxidative stress under elevated yet sublethal temperatures. We studied relationships between oxidative stress and HSPs in a physiological model by using Garra rufa (doctor fish), a fish species naturally acclimatized to different thermal conditions. We compared fish naturally living in a hot spring with relatively high water temperature (34.4±0.6°C) to those living in normal river water temperature (25.4±4.7°C), and found that levels of all the studied HSPs (HSP70, HSP60, HSP90, HSC70 and GRP75) were higher in fish living in elevated water temperature compared with normal river water temperature. In contrast, indicators of oxidative stress, including protein carbonyls and lipid hydroperoxides, were decreased in fish living in the elevated temperature, indicating that HSP levels are inversely associated with oxidative stress. The present results provide evidence that physiologically increased HSP levels provide protection against oxidative stress and enhance cytoprotection. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

The adrenocortical stress-response of Black-legged Kittiwake chicks in relation to dietary restrictions

USGS Publications Warehouse

Kitaysky, A.S.; Piatt, John F.; Wingfield, J.C.; Romano, M.

1999-01-01

In this study we examined hormonal responses of Black-legged Kittiwake (Rissa tridactyla) chicks to experimental variations in energy content and nutritional quality (low or high lipid to protein ratio, LPR) of their food. Starting at the age of 10 days, chicks were fed either high or low LPR fish at 30, 50, 70 and 100% of ad libitum energy intake. After 20 days of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where a baseline sample was taken immediately after taking a chick from the nest, and three additional blood samples were taken at intervals up to 50 min. Testosterone and corticosterone titres in plasma were measured via radioimmunoassay. We found that baseline testosterone levels were not significantly affected by the experimental treatments. Food-restricted chicks had elevated baseline and acute stress-induced levels of corticosterone compared to chicks fed ad libitum. An elevation of circulating levels of corticosterone in energetically stressed individuals was further magnified by low nutritional quality of food. Baseline and acute stress-induced corticosterone levels of chicks were negatively correlated with their fat reserves. We conclude that the physiological condition of Black-legged Kittiwake chicks can be assessed reliably by measuring circulating levels of corticosterone. We discuss short-and long-term effects of elevated corticosterone secretion in food-stressed nest-bound chicks.

The adrenocorical stress-response of Black-legged Kittiwake chicks in relation to dietary restrictions

USGS Publications Warehouse

Kitaysky, A.S.; Piatt, John F.; Wingfield, J.C.; Romano, M.

1999-01-01

In this study we examined hormonal responses of Black-legged Kittiwake (Rissa tridactyla) chicks to experimental variations in energy content and nutritional quality (low or high lipid to protein ratio, LPR) of their food. Starting at the age of 10 days, chicks were fed either high or low LPR fish at 30, 50, 70 and 100% of ad libitum energy intake. After 20 days of treatment, chicks were exposed to a standardized acute handling and restraint stress protocol, where a baseline sample was taken immediately after taking a chick from the nest, and three additional blood samples were taken at intervals up to 50 min. Testosterone and corticosterone titres in plasma were measured via radioimmunoassay. We found that baseline testosterone levels were not significantly affected by the experimental treatments. Food-restricted chicks had elevated baseline and acute stress-induced levels of corticosterone compared to chicks fed ad libitum. An elevation of circulating levels of corticosterone in energetically stressed individuals was further magnified by low nutritional quality of food. Baseline and acute stress-induced corticosterone levels of chicks were negatively correlated with their fat reserves. We conclude that the physiological condition of Black-legged Kittiwake chicks can be assessed reliably by measuring circulating levels of corticosterone. We discuss short- and long-term effects of elevated corticosterone secretion in food-stressed nest-bound chicks.

Increased stroke risk and lipoprotein(a) in a multiethnic community: the Northern Manhattan Stroke Study.

PubMed

Boden-Albala, Bernadette; Kargman, Douglas E; Lin, I-Feng; Paik, Myunghee C; Sacco, Ralph L; Berglund, Lars

2010-08-01

Elevated lipoprotein(a) [Lp(a)] is associated with ischemic stroke (IS) among Whites, but data is sparse for non-White populations. Using a population-based case-control study design with subjects from the Northern Manhattan Stroke Study, we assessed whether Lp(a) levels were independently associated with IS risk among Whites, Blacks and Hispanics. Lp(a) levels were measured in 317 IS cases (mean age 69 +/- 13 years; 56% women; 16% Whites, 31% Blacks and 52% Hispanics) and 413 community-based controls, matched by age, race/ethnicity and gender. In-person assessments included demographics, socioeconomic status, presence of vascular risk factors and fasting lipid levels. Logistic regression was used to determine the independent association of Lp(a) and IS. Stratified analyses investigated gender and race/ethnic differences. Mean Lp(a) levels were greater among cases than controls (46.3 +/- 41.0 vs. 38.9 +/- 38.2 mg/dl; p < 0.01). After adjusting for stroke risk factors (hypertension, diabetes mellitus, coronary artery disease, cigarette smoking), lipid levels, and socioeconomic status, Lp(a) levels > or =30 mg/dl were independently associated with an increased stroke risk in the overall cohort (adjusted odds ratio, OR, 1.8, 95% confidence interval, CI, 1.20-2.6; p = 0.004). There was a significant linear dose-response relationship between Lp(a) levels and IS risk. The association between IS risk and Lp(a) > or =30 mg/dl was more pronounced among men (adjusted OR 2.0, 95% CI 1.1-3.5; p = 0.02) and among Blacks (adjusted OR 2.7, 95% CI 1.2-6.2; p = 0.02). Elevated Lp(a) levels were significantly and independently associated with increased stroke risk, suggesting that Lp(a) is a risk factor for IS across White, Black and Hispanic race/ethnic groups. Copyright 2010 S. Karger AG, Basel.

Family Planning for women unable to tolerate oral contraceptives.

PubMed

Spellacy, W N

1974-04-08

Should women with a family history of diabetes or myocardial infarcation, or women with abnormal blood glucose or cholesterol levels receive oral contraceptives? There is clear evidence that oral contraceptives can alter both carbohydrate and lipid metabolism in certain women. The lipid alteration is mainly an elevation of the circulating triglyceride levels, and only rarely is cholesterol content altered. It is also clear from extensive research during the past ten years that women who already have subclinical abnormalities, either in their triglyceride levels (family hyperlipoproteinemia) or glucose tolerance, are at great risk for the development of clinical disease while using oral contraceptives. Accordingly, all pharmaceutical firms are required by the Food and Drug Administration to instruct physicians about these problems through the package inserts and other means. Specifically, the physician should be alerted by the patient's history, and then he should use the laboratory to confirm any suspicion of abnormalities of carbohydrate or lipid metabolism. If there is any abnormal blood glucose or triglyceride value, the oral contraceptives should not be prescribed. There are other forms of contraception available for child spacing. Mechanical contraceptives will not aggravate a metabolic disorder. A useful substitute then would be an intrauterine device plus vaginal foam. When the woman has completed her family, she should be all means be offered surgical sterilization as a permanent family planning technique.

Hypolipidemic effect of fruit fibers in rats fed with high dietary fat.

PubMed

Esmael, O A; Sonbul, S N; Kumosani, T A; Moselhy, S S

2015-03-01

The hypolipidemic effect of 10% fruit fibers in rats fed with high-fat diet (HFD) was evaluated. This study was conducted on a total of 50 male Albino rats divided into 10 equal groups fed with different types of dietary fruits. The feeding period lasted for 24 weeks. Fasting blood samples were collected and sera separated and subjected to lipid profile assay and atherogenic index. In addition, total antioxidant activity of different fruits was determined. The results obtained showed that pomegranate had higher content of antioxidants followed by apple, strawberry and guava compared with other fruits. Rats fed with 20% coconut oil showed a highly significant elevation in the levels of serum total cholesterol, low-density lipoprotein cholesterol and atherogenic factor while the level of high-density lipoprotein cholesterol was significantly decreased when compared with control rats. Histological examination revealed that there was a large lipid and cholesterol deposition in the livers of rats fed with HFD. The potential in lowering the levels of plasma total cholesterol and triglyceride is in the following order: pomegranate > apple > strawberry > guava > papaya > mandarin and orange. Accumulation of hepatic lipid droplets was diminished when compared with the HFD group. Also, antiatherogenic is better than the untreated groups. Accordingly these hypolipidemic effects may be due to high-fiber content and antioxidant activity of these fruits. © The Author(s) 2012.

Effect of Pterocarpus santalinus bark, on blood glucose, serum lipids, plasma insulin and hepatic carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats.

PubMed

Kondeti, Vinay Kumar; Badri, Kameswara Rao; Maddirala, Dilip Rajasekhar; Thur, Sampath Kumar Mekala; Fatima, Shaik Sameena; Kasetti, Ramesh Babu; Rao, Chippada Appa

2010-05-01

The present study was designed to investigate the effect of bark of Pterocarpus santalinus, an ethnomedicinal plant, on blood glucose, plasma insulin, serum lipids and the activities of hepatic glucose metabolizing enzymes in streptozotocin-induced diabetic rats. Streptozotocin-induced diabetic rats were treated (acute/short-term and long-term) with ethyl acetate:methanol fractions of ethanolic extract of the bark of P. santalinus. Fasting blood glucose, HbA(1C), plasma insulin and protein were estimated before and after the treatment, along with hepatic glycogen, and activities of hexokinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase and glucose-6-phosphate dehydrogenase. Further anti-hyperlipidemic activity was studied by measuring the levels of serum lipids and lipoproteins. Phytochemical analysis of active fraction showed the presence of flavonoids, glycosides and phenols. Biological testing of the active fraction demonstrated a significant antidiabetic activity by reducing the elevated blood glucose levels and glycosylated hemoglobin, improving hyperlipidemia and restoring the insulin levels in treated experimental induced diabetic rats. Further elucidation of mechanism of action showed improvement in the hepatic carbohydrate metabolizing enzymes after the treatment. Our present investigation suggests that active fraction of ethanolic extract of bark of P. santalinus decreases streptozotocin induced hyperglycemia by increasing glycolysis and decreasing gluconeogenesis. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Dyslipidaemia in nephrotic syndrome: mechanisms and treatment

PubMed Central

Agrawal, Shipra; Zaritsky, Joshua J.; Fornoni, Alessia; Smoyer, William E.

2018-01-01

Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9. In addition, there is an increase in the plasma levels of immature HDL particles and reduced cholesterol efflux. Studies from the past few years have markedly improved our understanding of the molecular pathogenesis of nephrotic syndrome associated dyslipidaemia, and also heightened our awareness of the associated exacerbated risks of cardiovascular complications, progressive kidney disease and thromboembolism. Despite the absence of clear guidelines regarding treatment, various strategies are being increasingly utilized, including statins, bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid apheresis, which seem to also induce partial or complete clinical remission of nephrotic syndrome in a substantial percentage of patients. Future potential treatments will likely also include inhibition of PCSK9 using recently developed anti PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting newly identified molecular regulators of lipid metabolism that are dysregulated in nephrotic syndrome. PMID:29176657

Korean red ginseng protects against neuronal damage induced by transient focal ischemia in rats

PubMed Central

BAN, JU YEON; KANG, SUNG WOOK; LEE, JONG SEOK; CHUNG, JOO-HO; KO, YOUNG GWAN; CHOI, HAN SUNG

2012-01-01

In the present study, we investigated the neuroprotective effect of Korean red ginseng (KRG) following focal brain ischemia/reperfusion injury, in relation to its antioxidant activities. The middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats was employed. The KRG extract (100 mg/kg, perorally) was administered once daily for 7 days following MCAO/R. The elevated levels of lipid peroxidation in the MCAO/R group were attenuated significantly in the KRG-administered group. The significantly depleted activity of the antioxidant enzymes glutathione peroxidase, superoxide dismutase and catalase was prevented in the KRG-administered group. In the neurobehavioral evaluation expressed as the modified neurological severity score and corner-turn test, the daily intake of KRG showed consistent and significant improvement in the neurological deficits for 7 days following MCAO/R injury. These results indicate that KRG has a neuroprotective effect against ischemia/reperfusion brain injury by reducing the level of lipid peroxidation and increasing the endogenous antioxidant enzymatic activity. PMID:22969953

Evaluation of dyslipidemia, lipid ratios, and atherogenic index as cardiovascular risk factors among semi-urban dwellers in Nigeria

PubMed Central

Olamoyegun, Michael Adeyemi; Oluyombo, Rotimi; Asaolu, Stephen Olabode

2016-01-01

Background and Objectives: The increasing frequency of cardiovascular disease (CVD) rests on the presence of major cardiovascular risk factors including dyslipidemia. This dyslipidemia is also a target for the prevention and treatment of many cardiovascular diseases. Hence, identification of individuals at risk of CVD is needed for early identification and prevention. The study was carried out to evaluate dyslipidemia using the lipid ratios and indices instead of just the conventional lipid profile. Methodology: It was a cross-sectional study with 699 participants recruited from semi-urban communities in Nigeria. Anthropometric indices, blood pressure, and fasting lipid profiles were determined. Abnormalities in lipid indices and lipid ratios with atherogenic index were also determined. SPSS software version 17.0 were used for analysis, P < 0.05 was considered statistically significant. Results: There were 699 participants with a mean age of 64.45 ± 15.53 years. Elevated total cholesterol, high low-density lipoprotein-cholesterol, elevated triglyceride, and low high-density lipoprotein were seen in 5.3%, 19.3%, 4.4%, and 76.3% of the participants, respectively. The Castelli's risk index-I (CRI-I) predicted the highest prevalence of predisposition to cardiovascular risk (47.8%) with females being at significantly higher risk (55.2% vs. 29.3%, P < 0.001). Atherogenic coefficient, CRI-II, CHOLIndex, atherogenic index of plasma (AIP) predicted a cardiovascular risk prevalence of 22.5%, 15.9%, 11.2%, and 11.0%, respectively, with no significant difference in between the sexes. Conclusions: Serum lipid ratios and AIP may be used in addition to lipid parameters in clinical practice to assess cardiovascular risks even when lipid profiles are apparently normal. AIP was more gender specific amidst the lipid ratios. PMID:27853034

Ecological engineering helps maximize function in algal oil production.

PubMed

Jackrel, Sara L; Narwani, Anita; Bentlage, Bastian; Levine, Robert B; Hietala, David C; Savage, Phillip E; Oakley, Todd H; Denef, Vincent J; Cardinale, Bradley J

2018-05-18

Algal biofuels have the potential to curb emissions of greenhouse gases from fossil fuels, but current growing methods fail to produce fuels that meet the multiple standards necessary for economical industrial use. For example, algae grown as monocultures for biofuel production have not simultaneously and economically achieved high yields of the high-quality, lipid-rich biomass desired for the industrial-scale production of bio-oil. Decades of study in the field of ecology have demonstrated that simultaneous increases in multiple functions, such as the quantity and quality of biomass, can occur in natural ecosystems by increasing biological diversity. Here we show that species consortia of algae can improve the production of bio-oil, which benefits from both high biomass yield and high quality of biomass rich in fatty acids. We explain the underlying causes of increased quantity and quality of algal biomass among species consortia by showing that, relative to monocultures, species consortia can differentially regulate lipid metabolism genes while growing to higher levels of biomass, in part due to greater utilization of nutrient resources. We identify multiple genes involved in lipid biosynthesis that are frequently upregulated in bicultures, and further show that these elevated levels of gene expression are highly predictive of the elevated levels in biculture relative to monoculture of multiple quality metrics of algal biomass. These results show that interactions between species can alter the expression of lipid metabolism genes, and further demonstrate that our understanding of diversity-function relationships from natural ecosystems can be harnessed to improve production of bio-oil. Importance section: Algal biofuels are one of the more promising forms of renewable energy. In our study, we investigate whether ecological interactions between species of microalgae regulate two important factors in cultivation - the biomass of the crop produced and quality of the biomass that is produced. We find that species interactions often improved production yields, especially the fatty acid content of the algal biomass, and that differentially expressed genes involved in fatty acid metabolism are predictive of improved quality metrics of bio-oil. Other studies have found that diversity often improves productivity and stability in agricultural and natural ecosystems. Our results provide further evidence that growing multi-species crops of microalgae may improve the production of high-quality biomass for bio-oil. Copyright © 2018 American Society for Microbiology.

Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: insight from the China Stroke Primary Prevention Trial.

PubMed

Liu, Yanhong; Kong, Xiangyi; Wang, Wen; Fan, Fangfang; Zhang, Yan; Zhao, Min; Wang, Yi; Wang, Yupeng; Wang, Yu; Qin, Xianhui; Tang, Genfu; Wang, Binyan; Xu, Xiping; Hou, Fan Fan; Gao, Wei; Sun, Ningling; Li, Jianping; Venners, Scott A; Jiang, Shanqun; Huo, Yong

2017-01-01

The aim of the present study was to examine the association between peripheral differential leukocyte counts and dyslipidemia in a Chinese hypertensive population. A total of 10,866 patients with hypertension were enrolled for a comprehensive assessment of cardiovascular risk factors using data from the China Stroke Primary Prevention Trial. Plasma lipid levels and total leukocyte, neutrophil, and lymphocyte counts were determined according to standard methods. Peripheral differential leukocyte counts were consistently and positively associated with serum total cholesterol (TC), LDL cholesterol (LDL-C), and TG levels (all P < 0.001 for trend), while inversely associated with HDL cholesterol levels (P < 0.05 for trend). In subsequent analyses where serum lipids were dichotomized (dyslipidemia/normolipidemia), we found that patients in the highest quartile of total leukocyte count (≥7.6 × 10 9 cells/l) had 1.64 times the risk of high TG [95% confidence interval (CI): 1.46, 1.85], 1.34 times the risk of high TC (95% CI: 1.20, 1.50), and 1.24 times the risk of high LDL-C (95% CI: 1.12, 1.39) compared with their counterparts in the lowest quartile of total leukocyte count. Similar patterns were also observed with neutrophils and lymphocytes. In summary, these findings indicate that elevated differential leukocyte counts are directly associated with serum lipid levels and increased odds of dyslipidemia. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Dopamine elevates intracellular zinc concentration in cultured rat embryonic cortical neurons through the cAMP-nitric oxide signaling cascade.

PubMed

Hung, Hui-Hsing; Kao, Lung-Sen; Liu, Pei-Shan; Huang, Chien-Chang; Yang, De-Ming; Pan, Chien-Yuan

2017-07-01

Zinc ion (Zn 2+ ), the second most abundant transition metal after iron in the body, is essential for neuronal activity and also induces toxicity if the concentration is abnormally high. Our previous results show that exposure of cultured cortical neurons to dopamine elevates intracellular Zn 2+ concentrations ([Zn 2+ ] i ) and induces autophagosome formation but the mechanism is not clear. In this study, we characterized the signaling pathway responsible for the dopamine-induced elevation of [Zn 2+ ] i and the effect of [Zn 2+ ] i in modulating the autophagy in cultured rat embryonic cortical neurons. N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a membrane-permeable Zn 2+ chelator, could rescue the cell death and suppress the autophagosome puncta number induced by dopamine. Dopamine treatment increased the lipidation level of the endogenous microtubule-associated protein 1A/1B-light chain 3 (LC3 II), an autophagosome marker. TPEN added 1h before, but not after, dopamine treatment suppressed the dopamine-induced elevation of LC3 II level. Inhibitors of the dopamine D1-like receptor, protein kinase A (PKA), and NOS suppressed the dopamine-induced elevation of [Zn 2+ ] i . PKA activators and NO generators directly increased [Zn 2+ ] i in cultured neurons. Through cell fractionation, proteins with m.w. values between 5 and 10kD were found to release Zn 2+ following NO stimulation. In addition, TPEN pretreatment and an inhibitor against PKA could suppress the LC3 II level increased by NO and dopamine, respectively. Therefore, our results demonstrate that dopamine-induced elevation of [Zn 2+ ] i is mediated by the D1-like receptor-PKA-NO pathway and is important in modulating the cell death and autophagy. Copyright © 2017 Elsevier Inc. All rights reserved.

Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity.

PubMed

de Melo, T S; Lima, P R; Carvalho, K M M B; Fontenele, T M; Solon, F R N; Tomé, A R; de Lemos, T L G; da Cruz Fonseca, S G; Santos, F A; Rao, V S; de Queiroz, M G R

2017-01-05

Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20-25 g (n=6-8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.

Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity

PubMed Central

de Melo, T.S.; Lima, P.R.; Carvalho, K.M.M.B.; Fontenele, T.M.; Solon, F.R.N.; Tomé, A.R.; de Lemos, T.L.G.; da Cruz Fonseca, S.G.; Santos, F.A.; Rao, V.S.; de Queiroz, M.G.R.

2017-01-01

Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20–25 g (n=6–8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses. PMID:28076453

Free Fatty Acids Link Metabolism and Regulation of the Insulin-Sensitizing Fibroblast Growth Factor-21

PubMed Central

Mai, Knut; Andres, Janin; Biedasek, Katrin; Weicht, Jessica; Bobbert, Thomas; Sabath, Markus; Meinus, Sabine; Reinecke, Franziska; Möhlig, Matthias; Weickert, Martin O.; Clemenz, Markus; Pfeiffer, Andreas F.H.; Kintscher, Ulrich; Spuler, Simone; Spranger, Joachim

2009-01-01

OBJECTIVE Fibroblast growth factor (FGF)-21 improves insulin sensitivity and lipid metabolism in obese or diabetic animal models, while human studies revealed increased FGF-21 levels in obesity and type 2 diabetes. Given that FGF-21 has been suggested to be a peroxisome proliferator–activator receptor (PPAR) α–dependent regulator of fasting metabolism, we hypothesized that free fatty acids (FFAs), natural agonists of PPARα, might modify FGF-21 levels. RESEARCH DESIGN AND METHODS The effect of fatty acids on FGF-21 was investigated in vitro in HepG2 cells. Within a randomized controlled trial, the effects of elevated FFAs were studied in 21 healthy subjects (13 women and 8 men). Within a clinical trial including 17 individuals, the effect of insulin was analyzed using an hyperinsulinemic-euglycemic clamp and the effect of PPARγ activation was studied subsequently in a rosiglitazone treatment trial over 8 weeks. RESULTS Oleate and linoleate increased FGF-21 expression and secretion in a PPARα-dependent fashion, as demonstrated by small-interfering RNA–induced PPARα knockdown, while palmitate had no effect. In vivo, lipid infusion induced an increase of circulating FGF-21 in humans, and a strong correlation between the change in FGF-21 levels and the change in FFAs was observed. An artificial hyperinsulinemia, which was induced to delineate the potential interaction between elevated FFAs and hyperinsulinemia, revealed that hyperinsulinemia also increased FGF-21 levels in vivo, while rosiglitazone treatment had no effect. CONCLUSIONS The results presented here offer a mechanism explaining the induction of the metabolic regulator FGF-21 in the fasting situation but also in type 2 diabetes and obesity. PMID:19401423

Effect of Hibiscus sabdariffa extract on high fat diet-induced obesity and liver damage in hamsters.

PubMed

Huang, To-Wei; Chang, Chia-Ling; Kao, Erl-Shyh; Lin, Jenq-Horng

2015-01-01

Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE) in vivo. Eight-weeks-old male mice were divided into six groups (n=8 per group) and were fed either normal feed, a high fat diet (HFD), HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity.

Effect of Hibiscus sabdariffa extract on high fat diet–induced obesity and liver damage in hamsters

PubMed Central

Huang, To-Wei; Chang, Chia-Ling; Kao, Erl-Shyh; Lin, Jenq-Horng

2015-01-01

Background Obesity is a chronic metabolic disorder associated with an increase in adipogenesis and often accompanied with fatty liver disease. Objective In this study, we investigated the anti-obesity effects of Hibiscus sabdariffa water extract (HSE) in vivo. Method Eight-weeks-old male mice were divided into six groups (n=8 per group) and were fed either normal feed, a high fat diet (HFD), HFD supplemented with different concentrations of HSE, or HFD supplemented with anthocyanin. After 10 weeks of feeding, all the blood and livers were collected for further analysis. Results Mesocricetus auratus hamster fed with a high-fat diet developed symptoms of obesity, as determined from their body weight change and from their plasma lipid levels. Meanwhile, HSE treatment reduced fat accumulation in the livers of hamsters fed with HFD in a concentration-dependent manner. Administration of HSE reduced the levels of liver cholesterol and triglycerides, which were elevated by HFD. Analysis of the effect of HSE on paraoxonase 1, an antioxidant liver enzyme, revealed that HSE potentially regulates lipid peroxides and protects organs from oxidation-associated damage. The markers of liver damage such as serum alanine aminotransferase and aspartate aminotransferase levels that were elevated by HFD were also reduced on HSE treatment. The effects of HSE were as effective as treatment with anthocyanin; therefore the anthocyanins present in the HSE may play a crucial role in the protection established against HFD-induced obesity. Conclusions In conclusion HSE administration constitutes an effective and viable treatment strategy against the development and consequences of obesity. PMID:26475512

Progressive sensorineural hearing loss, subjective tinnitus and vertigo caused by elevated blood lipids.

PubMed

Pulec, J L; Pulec, M B; Mendoza, I

1997-10-01

The otologist frequently sees patients with progressive sensorineural hearing loss, subjective aural tinnitus and vertigo with no apparent cause. Elevated blood lipids may be a cause of inner ear malfunction on a biochemical basis. To establish the true incidence of this condition, all new patients (4,251) seen during an eight-year period were evaluated; of these, 2,332 patients had complaints of inner ear disease. All had a complete neurotologic examination, appropriate audiometric and vestibular studies and imaging, and blood tests including lipid phenotype studies. Hyperlipoproteinemia was found in 120 patients (5.1%). Most patients were found to be overweight and had additional coexisting conditions such as diabetes mellitus. Treatment with vasodilators and a 500-calorie, high-protein, low-carbohydrate diet yielded improvement of symptoms in 83% of patients within five months of initiation of treatment.

Antihyperlipidemic effects of Pleurotus ostreatus (oyster mushrooms) in HIV-infected individuals taking antiretroviral therapy.

PubMed

Abrams, Donald I; Couey, Paul; Shade, Starley B; Kelly, Mary Ellen; Kamanu-Elias, Nnemdi; Stamets, Paul

2011-08-10

Antiretroviral treatment (ART) regimens in HIV patients commonly cause significant lipid elevations, including increases in both triglycerides and cholesterol. Standard treatments for hypercholesterolemia include the HMG CoA reductase inhibitors, or "statins." Because many ART agents and statins share a common metabolic pathway that uses the cytochrome P450 enzyme system, coadministration of ART with statins could increase statin plasma levels significantly. The oyster mushroom, Pleurotus ostreatus, has been shown in animal models to decrease lipid levels--a finding that has been supported by preliminary data in a small human trial. To assess the safety and efficacy of P. ostreatus in patients with HIV and ART-induced hyperlipidemia, a single-arm, open-label, proof-of-concept study of 8 weeks' duration with a target enrollment of 20 subjects was conducted. Study patients with ART-induced elevated non-HDL cholesterol levels (> 160 mg/dL) were enrolled. Participants received packets of freeze-dried P. ostreatus (15 gm/day) to be administered orally for the 8 week trial period. Lipid levels were drawn every two weeks to assess efficacy. Safety assessments included self-reported incidence of muscle aches and measurement of liver and muscle enzymes. Mean within-person change in lipid levels were estimated using generalized estimating equations to account for repeated observations on individuals. A 30 mg/dL decrease in non-HDL cholesterol was deemed clinically significant. 126 patients were screened to enroll 25, of which 20 completed the 8-week study. The mean age was 46.4 years (36-60). Patients had a mean 13.7 yrs of HIV infection. Mean non-HDL cholesterol was 204.5 mg/dL at day 0 and 200.2 mg/dL at day 56 (mean within-person change = -1.70; 95% confidence interval (CI) = -17.4, 14.0). HDL cholesterol levels increased from 37.8 mg/dL at day 0 to 40.4 mg/dL on day 56 (mean within-person change = 2.6; 95% CI = -0.1, 5.2). Triglycerides dropped from 336.4 mg/dL on day 0 to 273.4 mg/dL on day 56 (mean within-person change = -63.0; 95% CI = -120.9, -5.1). Only 3 individuals achieved a sustained clinically significant (30 mg/dL) decline in non-HDL cholesterol after 8 weeks of therapy. There were no adverse experiences reported other than patients' distaste for the preparation. Liver function tests and muscle enzymes were not affected by the 8 weeks of treatment. Pleurotus ostreatus as administered in this experiment did not lower non-HDL cholesterol in HIV patients with ART-induced hypercholesterolemia. Small changes in HDL and triglycerides were not of a clinical magnitude to warrant further study.

Involvement of small heat shock proteins, trehalose, and lipids in the thermal stress management in Schizosaccharomyces pombe.

PubMed

Glatz, Attila; Pilbat, Ana-Maria; Németh, Gergely L; Vince-Kontár, Katalin; Jósvay, Katalin; Hunya, Ákos; Udvardy, Andor; Gombos, Imre; Péter, Mária; Balogh, Gábor; Horváth, Ibolya; Vígh, László; Török, Zsolt

2016-03-01

Changes in the levels of three structurally and functionally different important thermoprotectant molecules, namely small heat shock proteins (sHsps), trehalose, and lipids, have been investigated upon heat shock in Schizosaccharomyces pombe. Both α-crystallin-type sHsps (Hsp15.8 and Hsp16) were induced after prolonged high-temperature treatment but with different kinetic profiles. The shsp null mutants display a weak, but significant, heat sensitivity indicating their importance in the thermal stress management. The heat induction of sHsps is different in wild type and in highly heat-sensitive trehalose-deficient (tps1Δ) cells; however, trehalose level did not show significant alteration in shsp mutants. The altered timing of trehalose accumulation and induction of sHsps suggest that the disaccharide might provide protection at the early stage of the heat stress while elevated amount of sHsps are required at the later phase. The cellular lipid compositions of two different temperature-adapted wild-type S. pombe cells are also altered according to the rule of homeoviscous adaptation, indicating their crucial role in adapting to the environmental temperature changes. Both Hsp15.8 and Hsp16 are able to bind to different lipids isolated from S. pombe, whose interaction might provide a powerful protection against heat-induced damages of the membranes. Our data suggest that all the three investigated thermoprotectant macromolecules play a pivotal role during the thermal stress management in the fission yeast.

Serum cholesterol and triglyceride concentrations in diabetic patients with subclinical hypothyroidism.

PubMed

Díez, Juan J; Iglesias, Pedro

2014-10-01

To assess whether subclinical hypothyroidism is associated to elevations in serum cholesterol and triglyceride levels in patients with type 2 diabetes. From a total population of 1,112 patients with type 2 diabetes screened for thyroid dysfunction (thyrotropin measurement), a group of 325 patients with normal thyroid function and another group of 29 patients with subclinical hypothyroidism were selected. No patient had known dyslipidemia or was taking lipid lowering medication. Patients with subclinical hypothyroidism had serum levels of total cholesterol (4.88 ± 0.74 mmol/L), HDL cholesterol (1.37 ± 0.34 mmol/L), LDL cholesterol (2.94 ± 0.58 mmol/L), and triglycerides (1.05 [0.88-1.41] mmol/L) that did not significantly differ from those found in euthyroid patients (4.79 ± 0.83, 1.33 ± 0.36, 2.87 ± 0.76, and 1.11 [0.81-1.43] mmol/L, respectively). Multiple regression analysis showed no association between TSH and serum lipid levels. These results suggest that, in our population, there are no significant differences in serum cholesterol and triglyceride levels between diabetic patients with normal and reduced thyroid function. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Flaxseed oil as a neuroprotective agent on lead acetate-induced monoamineric alterations and neurotoxicity in rats.

PubMed

Abdel Moneim, Ahmed E

2012-09-01

Lead remains a considerable occupational and public health problem, which is known to cause a number of adverse effects in both man and animals. Here, the neuroprotective effect of flaxseed oil (1,000 mg/kg) on lead acetate (20 mg/kg) induced alternation in monoamines and brain oxidative stress was examined in rats. The levels of lead, dopamine (DA), norepinephrine (NE), serotonin (5-HT), lipid peroxidation, nitrite/nitrate (NO), and glutathione (GSH) were determined; also, the activity of acetylcholinesterase (AChE) and Na(+)-K(+)-ATPase were estimated on different brain regions of adult male albino rats. The level of lead was markedly elevated in different brain regions of rats. This leads to enhancement of lipid peroxidation and NO production in brain with concomitant reduction in AChE activity and GSH level. In addition, the levels of DA, NE, and 5-HT were decreased in the brain. These findings were associated with BAX over expression. Treatment of rats with flaxseed oil induced a marked improvement in most of the studied parameters as well as the immunohistochemistry features. These data indicated that dietary flaxseed oil provide protection against lead-induced oxidative stress and neurotoxic effects.

Local Matrix Metalloproteinase 9 Level Determines Early Clinical Presentation of ST-Segment-Elevation Myocardial Infarction.

PubMed

Nishiguchi, Tsuyoshi; Tanaka, Atsushi; Taruya, Akira; Emori, Hiroki; Ozaki, Yuichi; Orii, Makoto; Shiono, Yasutsugu; Shimamura, Kunihiro; Kameyama, Takeyoshi; Yamano, Takashi; Yamaguchi, Tomoyuki; Matsuo, Yoshiki; Ino, Yasushi; Kubo, Takashi; Hozumi, Takeshi; Hayashi, Yasushi; Akasaka, Takashi

2016-12-01

Early clinical presentation of ST-segment-elevation myocardial infarction (STEMI) and non-ST-segment-elevation myocardial infarction affects patient management. Although local inflammatory activities are involved in the onset of MI, little is known about their impact on early clinical presentation. This study aimed to investigate whether local inflammatory activities affect early clinical presentation. This study comprised 94 and 17 patients with MI (STEMI, 69; non-STEMI, 25) and stable angina pectoris, respectively. We simultaneously investigated the culprit lesion morphologies using optical coherence tomography and inflammatory activities assessed by shedding matrix metalloproteinase 9 (MMP-9) and myeloperoxidase into the coronary circulation before and after stenting. Prevalence of plaque rupture, thin-cap fibroatheroma, and lipid arc or macrophage count was higher in patients with STEMI and non-STEMI than in those with stable angina pectoris. Red thrombus was frequently observed in STEMI compared with others. Local MMP-9 levels were significantly higher than systemic levels (systemic, 42.0 [27.9-73.2] ng/mL versus prestent local, 69.1 [32.2-152.3] ng/mL versus poststent local, 68.0 [35.6-133.3] ng/mL; P<0.01). Poststent local MMP-9 level was significantly elevated in patients with STEMI (STEMI, 109.9 [54.5-197.8] ng/mL versus non-STEMI: 52.9 [33.0-79.5] ng/mL; stable angina pectoris, 28.3 [14.2-40.0] ng/mL; P<0.01), whereas no difference was observed in the myeloperoxidase level. Poststent local MMP-9 and the presence of red thrombus are the independent determinants for STEMI in multivariate analysis. Local MMP-9 level could determine the early clinical presentation in patients with MI. Local inflammatory activity for atherosclerosis needs increased attention. © 2016 American Heart Association, Inc.

Serum levels of brominated flame retardants (BFRs: PBDE, HBCD) and influence of dietary factors in a population-based study on Swedish adults.

PubMed

Bjermo, Helena; Aune, Marie; Cantillana, Tatiana; Glynn, Anders; Lind, P Monica; Ridefelt, Peter; Darnerud, Per Ola

2017-01-01

The aim of this study was to investigate associations between serum concentrations of brominated flame retardants and personal characteristics, including diet, in adults participating in a population-based study in Sweden 2010-11. Moreover, observed concentrations were used in a health risk assessment, using published health-based reference values. Serum samples of 170 adult individuals of both sexes were analyzed for 10 PBDE congeners and HBCD by GC-MS. When including concentrations between LOD and LOQ, highest median serum concentration was observed for BDE-153 (1.2 ng/g serum lipid), followed by BDE-209 (0.95 ng/g lipid), BDE-47 (0.49 ng/g lipid) and BDE-100 (0.21 ng/g lipid). Median concentration of HBCD was 0.10 ng/g lipid. A few markedly elevated concentrations of BDE-209, HBCD (77-78 ng/g lipid) and BDE-47 (44 ng/g lipid) were observed. The only statistical significant findings were higher BDE-153 concentrations in men than in women, and positive associations between serum BDE-153 concentrations and consumption of fish (total), beef, mutton and poultry. PBDE concentrations were in accordance with concentrations reported in other European countries but generally lower than those found in North America. Median PBDE serum concentrations observed in adults from Sweden suggest sufficient health protection, when compared with published health-based reference values, although some outliers with high serum concentrations had lower safety margins. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Heat Stress Dictates Microbial Lipid Composition along a Thermal Gradient in Marine Sediments

PubMed Central

Sollich, Miriam; Yoshinaga, Marcos Y.; Häusler, Stefan; Price, Roy E.; Hinrichs, Kai-Uwe; Bühring, Solveig I.

2017-01-01

Temperature exerts a first-order control on microbial populations, which constantly adjust the fluidity and permeability of their cell membrane lipids to minimize loss of energy by ion diffusion across the membrane. Analytical advances in liquid chromatography coupled to mass spectrometry have allowed the detection of a stunning diversity of bacterial and archaeal lipids in extreme environments such as hot springs, hydrothermal vents and deep subsurface marine sediments. Here, we investigated a thermal gradient from 18 to 101°C across a marine sediment field and tested the hypothesis that cell membrane lipids provide a major biochemical basis for the bioenergetics of archaea and bacteria under heat stress. This paper features a detailed lipidomics approach with the focus on membrane lipid structure-function. Membrane lipids analyzed here include polar lipids of bacteria and polar and core lipids of archaea. Reflecting the low permeability of their ether-linked isoprenoids, we found that archaeal polar lipids generally dominate over bacterial lipids in deep layers of the sediments influenced by hydrothermal fluids. A close examination of archaeal and bacterial lipids revealed a membrane quandary: not only low permeability, but also increased fluidity of membranes are required as a unified property of microbial membranes for energy conservation under heat stress. For instance, bacterial fatty acids were composed of longer chain lengths in concert with higher degree of unsaturation while archaea modified their tetraethers by incorporation of additional methyl groups at elevated sediment temperatures. It is possible that these configurations toward a more fluidized membrane at elevated temperatures are counterbalanced by the high abundance of archaeal glycolipids and bacterial sphingolipids, which could reduce membrane permeability through strong intermolecular hydrogen bonding. Our results provide a new angle for interpreting membrane lipid structure-function enabling archaea and bacteria to survive and grow in hydrothermal systems. PMID:28878741

Protective effect of Spirulina platensis against cell damage and apoptosis in hepatic tissue caused by high fat diet.

PubMed

Yigit, F; Gurel-Gurevin, E; Isbilen-Basok, B; Esener, O B B; Bilal, T; Keser, O; Altiner, A; Yilmazer, N; Ikitimur-Armutak, E I

2016-01-01

Spirulina platensis is a microalga that may be a source of antioxidants that can reduce body fat deposition. Consumption of a high fat diet produces elevated blood lipid levels, inflammation and apoptosis. We investigated the possible effects of S. platensis on the blood lipid profile, and liver inflammation and apoptosis in rats fed a high fat diet. Sixty-four young male rats were divided into eight equal groups. The control group was fed a basic diet. The experimental groups were fed a diet for 60 days that was prepared by mixing variable amounts of 43% vegetable oil and 10% cholesterol with or without 3% S. platensis mixed with the basal diet. Blood and liver tissue samples were collected from each animal. Serum samples were used to analyze lipid parameters, total antioxidant status and total oxidant status. iNOS and eNOS were determined by immunohistochemistry. TUNEL staining was used to detect apoptosis to investigate a possible connection between inflammation and apoptosis in the liver tissue. The relations between fat deposition and liver degeneration were assessed by Sirius red staining and alpha-smooth muscle actin immunostaining. S. platensis reduced serum HDL-C, LDL-C and triglyceride, increased HDL-C levels in rats fed a high fat diet to near control levels, and reduced iNOS levels and increased eNOS levels in the liver tissue compared to vegetable oil and cholesterol treated groups. The apoptotic index was reduced in the groups that were fed a high fat or a basic diet when supplemented with S. platensis.

Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians.

PubMed

Meor Anuar Shuhaili, Meor Fairuz Rizal; Samsudin, Intan Nureslyna; Stanslas, Johnson; Hasan, Shariful; Thambiah, Subashini C

2017-04-01

The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians. PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles. CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group. The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

Juvenile hormone and insulin suppress lipolysis between periods of lactation during tsetse fly pregnancy

PubMed Central

Michalkova, Veronika; Mireji, Paul; Attardo, Geoffrey M.; Moulton, John K.; Wilson, Thomas G.; Aksoy, Serap

2014-01-01

Tsetse flies are viviparous insects that nurture a single intrauterine progeny per gonotrophic cycle. The developing larva is nourished by the lipid-rich, milk-like secretions from a modified female accessory gland (milk gland). An essential feature of the lactation process involves lipid mobilization for incorporation into the milk. In this study, we examined roles for juvenile hormone (JH) and insulin/IGF-like (IIS) signaling pathways during tsetse pregnancy. In particular, we examined the roles for these pathways in regulating lipid homeostasis during transitions between non-lactating (dry) and lactating periods. The dry period occurs over the course of oogenesis and embryogenesis, while the lactation period spans intrauterine larvigenesis. Genes involved in the JH and IIS pathways were upregulated during dry periods, correlating with lipid accumulation between bouts of lactation. RNAi suppression of Forkhead Box Sub Group O (FOXO) expression impaired lipolysis during tsetse lactation and reduced fecundity. Similar reduction of the JH receptor Methoprene tolerant (Met), but not its paralog germ cell expressed (gce), reduced lipid accumulation during dry periods, indicating functional divergence between Met and gce during tsetse reproduction. Reduced lipid levels following Met knockdown led to impaired fecundity due to inadequate fat reserves at the initiation of milk production. Both the application of the JH analog (JHA) methoprene and injection of insulin into lactating females increased stored lipids by suppressing lipolysis and reduced transcripts of lactation-specific genes, leading to elevated rates of larval abortion. To our knowledge, this study is the first to address the molecular physiology of JH and IIS in a viviparous insect, and specifically to provide a role for JH signaling through Met in the regulation of lipid metabolism. PMID:23499946

Juvenile hormone and insulin suppress lipolysis between periods of lactation during tsetse fly pregnancy.

PubMed

Baumann, Aaron A; Benoit, Joshua B; Michalkova, Veronika; Mireji, Paul; Attardo, Geoffrey M; Moulton, John K; Wilson, Thomas G; Aksoy, Serap

2013-06-15

Tsetse flies are viviparous insects that nurture a single intrauterine progeny per gonotrophic cycle. The developing larva is nourished by the lipid-rich, milk-like secretions from a modified female accessory gland (milk gland). An essential feature of the lactation process involves lipid mobilization for incorporation into the milk. In this study, we examined roles for juvenile hormone (JH) and insulin/IGF-like (IIS) signaling pathways during tsetse pregnancy. In particular, we examined the roles for these pathways in regulating lipid homeostasis during transitions between non-lactating (dry) and lactating periods. The dry period occurs over the course of oogenesis and embryogenesis, while the lactation period spans intrauterine larvigenesis. Genes involved in the JH and IIS pathways were upregulated during dry periods, correlating with lipid accumulation between bouts of lactation. RNAi suppression of Forkhead Box Sub Group O (FOXO) expression impaired lipolysis during tsetse lactation and reduced fecundity. Similar reduction of the JH receptor Methoprene tolerant (Met), but not its paralog germ cell expressed (gce), reduced lipid accumulation during dry periods, indicating functional divergence between Met and gce during tsetse reproduction. Reduced lipid levels following Met knockdown led to impaired fecundity due to inadequate fat reserves at the initiation of milk production. Both the application of the JH analog (JHA) methoprene and injection of insulin into lactating females increased stored lipids by suppressing lipolysis and reduced transcripts of lactation-specific genes, leading to elevated rates of larval abortion. To our knowledge, this study is the first to address the molecular physiology of JH and IIS in a viviparous insect, and specifically to provide a role for JH signaling through Met in the regulation of lipid metabolism during insect lactation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss.

PubMed

Graham, Lucia S; Parhami, Farhad; Tintut, Yin; Kitchen, Christina M R; Demer, Linda L; Effros, Rita B

2009-11-01

Osteoporosis is a systemic disease that is associated with increased morbidity, mortality and health care costs. Whereas osteoclasts and osteoblasts are the main regulators of bone homeostasis, recent studies underscore a key role for the immune system, particularly via activation-induced T lymphocyte production of receptor activator of NFkappaB ligand (RANKL). Well-documented as a mediator of T lymphocyte/dendritic cell interactions, RANKL also stimulates the maturation and activation of bone-resorbing osteoclasts. Given that lipid oxidation products mediate inflammatory and metabolic disorders such as osteoporosis and atherosclerosis, and since oxidized lipids affect several T lymphocyte functions, we hypothesized that RANKL production might also be subject to modulation by oxidized lipids. Here, we show that short term exposure of both unstimulated and activated human T lymphocytes to minimally oxidized low density lipoprotein (LDL), but not native LDL, significantly enhances RANKL production and promotes expression of the lectin-like oxidized LDL receptor-1 (LOX-1). The effect, which is also observed with 8-iso-Prostaglandin E2, an inflammatory isoprostane produced by lipid peroxidation, is mediated via the NFkappaB pathway, and involves increased RANKL mRNA expression. The link between oxidized lipids and T lymphocytes is further reinforced by analysis of hyperlipidemic mice, in which bone loss is associated with increased RANKL mRNA in T lymphocytes and elevated RANKL serum levels. Our results suggest a novel pathway by which T lymphocytes contribute to bone changes, namely, via oxidized lipid enhancement of RANKL production. These findings may help elucidate clinical associations between cardiovascular disease and decreased bone mass, and may also lead to new immune-based approaches to osteoporosis.

Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress.

PubMed

Koncsos, Gábor; Varga, Zoltán V; Baranyai, Tamás; Boengler, Kerstin; Rohrbach, Susanne; Li, Ling; Schlüter, Klaus-Dieter; Schreckenberg, Rolf; Radovits, Tamás; Oláh, Attila; Mátyás, Csaba; Lux, Árpád; Al-Khrasani, Mahmoud; Komlódi, Tímea; Bukosza, Nóra; Máthé, Domokos; Deres, László; Barteková, Monika; Rajtík, Tomáš; Adameová, Adriana; Szigeti, Krisztián; Hamar, Péter; Helyes, Zsuzsanna; Tretter, László; Pacher, Pál; Merkely, Béla; Giricz, Zoltán; Schulz, Rainer; Ferdinandy, Péter

2016-10-01

Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect of prediabetes on cardiac function and to characterize parameters and pathways associated with deteriorated cardiac performance. Long-Evans rats were fed with either control or high-fat chow for 21 wk and treated with a single low dose (20 mg/kg) of streptozotocin at week 4 High-fat and streptozotocin treatment induced prediabetes as characterized by slightly elevated fasting blood glucose, impaired glucose and insulin tolerance, increased visceral adipose tissue and plasma leptin levels, as well as sensory neuropathy. In prediabetic animals, a mild diastolic dysfunction was observed, the number of myocardial lipid droplets increased, and left ventricular mass and wall thickness were elevated; however, no molecular sign of fibrosis or cardiac hypertrophy was shown. In prediabetes, production of reactive oxygen species was elevated in subsarcolemmal mitochondria. Expression of mitofusin-2 was increased, while the phosphorylation of phospholamban and expression of Bcl-2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3, a marker of mitophagy) decreased. However, expression of other markers of cardiac auto- and mitophagy, mitochondrial dynamics, inflammation, heat shock proteins, Ca 2+ /calmodulin-dependent protein kinase II, mammalian target of rapamycin, or apoptotic pathways were unchanged in prediabetes. This is the first comprehensive analysis of cardiac effects of prediabetes indicating that mild diastolic dysfunction and cardiac hypertrophy are multifactorial phenomena that are associated with early changes in mitophagy, cardiac lipid accumulation, and elevated oxidative stress and that prediabetes-induced oxidative stress originates from the subsarcolemmal mitochondria. Copyright © 2016 the American Physiological Society.

Non-lipid effects of rosuvastatin-fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia.

PubMed

Lee, Sang-Hak; Cho, Kyoung-Im; Kim, Jang-Young; Ahn, Young Keun; Rha, Seung-Woon; Kim, Yong-Jin; Choi, Yun-Seok; Choi, Si Wan; Jeon, Dong Woon; Min, Pil-Ki; Choi, Dong-Ju; Baek, Sang Hong; Kim, Kwon Sam; Byun, Young Sup; Jang, Yangsoo

2012-03-01

The aim of this study is to compare the non-lipid effects of rosuvastatin-fenofibrate combination therapy with rosuvastatin monotherapy in high-risk Asian patients with mixed hyperlipidemia. A total of 236 patients were initially screened. After six weeks of diet and life style changes, 180 of these patients were randomly assigned to receive one of two regimens: rosuvastatin 10 mg plus fenofibrate 160 mg or rosuvastatin 10 mg. The primary outcome variables were the incidences of muscle or liver enzyme elevation. The patients were followed for 24 weeks during drug treatment and for an additional four weeks after drug discontinuation. The rates of the primary outcome variables were similar between the two groups (2.8% and 3.9% in the combination and the rosuvastatin groups, respectively, p=1.00). The combination group had more, but not significantly, common treatment-related adverse events (AEs) (13.3% and 5.6%, respectively) and drug discontinuation due to AEs (10.0% and 3.3%, respectively) than the rosouvastatin group. Combination therapy was associated with higher elevations in homocysteine, blood urea nitrogen, and serum creatinine, whereas elevation in alanine aminotransferase was greater in the rosuvastatin group. Leukocyte count and hemoglobin level decreased to a greater extent in the combination group. The combination group showed greater reductions in TG and elevation in HDL-cholesterol. In our study population, the rosuvastatin-fenofibrate combination resulted in comparable incidences of myo- or hepatotoxicity as rosuvastatin monotherapy. However, this combination may need to be used with caution in individuals with underlying pathologies such as renal dysfunction (NCT01414803). Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effect of bacoside A on membrane-bound ATPases in the brain of rats exposed to cigarette smoke.

PubMed

Anbarasi, K; Vani, G; Balakrishna, K; Devi, C S Shyamala

2005-01-01

Membrane-bound enzymes play a vital role in neuronal function through maintenance of membrane potential and impulse propagation. We have evaluated the harmful effects of chronic cigarette smoking on membrane-bound ATPases and the protective effect of Bacoside A in rat brain. Adult male albino rats were exposed to cigarette smoke for a period of 12 weeks and simultaneously administered with Bacoside A (the active principle isolated from Bacopa monniera) at a dosage of 10 mg/kg b.w/day, p.o. The levels of lipid peroxides as marker for evaluating the extent of membrane damage, the activities of Na+/K+-ATPase, Ca2+-ATPase and Mg2+-ATPase, and associated cations sodium (Na+), potassium (K+), calcium (Ca2+), and magnesium (Mg2+) were investigated in the brain. Neuronal membrane damage was evident from the elevated levels of lipid peroxides and decreased activities of membrane-bound enzymes. Disturbances in the electrolyte balance with accumulation of Na+ and Ca2+ and depletion of K+ and Mg2+ were also observed. Administration of Bacoside A inhibited lipid peroxidation, improved the activities of ATPases, and maintained the ionic equilibrium. The results of our study indicate that Bacoside A protects the brain from cigarette smoking induced membrane damage. Copyright 2005 Wiley Periodicals, Inc.

Reduced cognitive function, increased blood-brain-barrier transport and inflammatory responses, and altered brain metabolites in LDLr -/-and C57BL/6 mice fed a western diet

PubMed Central

Lee, Linda L.; Puchowicz, Michelle; Golub, Mari S.; Befroy, Douglas E.; Wilson, Dennis W.; Anderson, Steven; Cline, Gary; Bini, Jason; Borkowski, Kamil; Knotts, Trina A.; Rutledge, John C.

2018-01-01

Recent work suggests that diet affects brain metabolism thereby impacting cognitive function. Our objective was to determine if a western diet altered brain metabolism, increased blood-brain barrier (BBB) transport and inflammation, and induced cognitive impairment in C57BL/6 (WT) mice and low-density lipoprotein receptor null (LDLr -/-) mice, a model of hyperlipidemia and cognitive decline. We show that a western diet and LDLr -/- moderately influence cognitive processes as assessed by Y-maze and radial arm water maze. Also, western diet significantly increased BBB transport, as well as microvessel factor VIII in LDLr -/- and microglia IBA1 staining in WT, both indicators of activation and neuroinflammation. Interestingly, LDLr -/- mice had a significant increase in 18F- fluorodeoxyglucose uptake irrespective of diet and brain 1H-magnetic resonance spectroscopy showed increased lactate and lipid moieties. Metabolic assessments of whole mouse brain by GC/MS and LC/MS/MS showed that a western diet altered brain TCA cycle and β-oxidation intermediates, levels of amino acids, and complex lipid levels and elevated proinflammatory lipid mediators. Our study reveals that the western diet has multiple impacts on brain metabolism, physiology, and altered cognitive function that likely manifest via multiple cellular pathways. PMID:29444171

Effect of Trimethylamine N-Oxide on Interfacial Electrostatics at Phospholipid Monolayer-Water Interfaces and Its Relevance to Cardiovascular Disease.

PubMed

Mondal, Jahur A

2016-05-05

Trimethylamine N-oxide (TMAO), a metabolite of choline containing dietary nutrients which are abundant in red meat, egg, and other animal foods, increases the risk of cardiovascular disease (e.g., atherosclerosis) by boosted accumulation of fatty deposits on artery wall. Hence, for the molecular level elucidation of the pathogenesis of atherosclerosis, it is important to understand the effect of TMAO at the endothelial cell membrane-blood interface (artery wall). Heterodyne-detected vibrational sum frequency generation (HD-VSFG) study of a zwitterionic phosphatidylcholine (PC) lipid monolayer-water interface (mimic of endothelial membrane-blood interface) shows that the interfacial water becomes increasingly H-up oriented in the presence of TMAO in the aqueous phase, revealing a dramatic change in the interfacial electrostatics. Examinations of charged lipid interfaces show that TMAO screens anionic phosphate less effectively than cationic choline, which confirms that TMAO increases the relative influence of the anionic phosphate by preferential screening of the cationic choline at the zwitterionic PC lipid interface where the phosphate and choline groups are simultaneously present. Together, it is conceivable that at an elevated TMAO level in serum would modify the electrostatics at the endothelial cell membrane-blood interface (artery wall), which may affect the influx/efflux of fatty deposits on artery wall, setting the stage for atherosclerosis.

Direct correlation between serum homocysteine level and insulin resistance index in patients with subclinical hypothyroidism: Does subclinical hypothyroidism increase the risk of diabetes and cardio vascular disease together?

PubMed

Ebrahimpour, Anahita; Vaghari-Tabari, Mostafa; Qujeq, Durdi; Moein, Soheila; Moazezi, Zoleikha

2018-05-05

Subclinical hypothyroidism known as mild thyroid disorder without significant sign and symptoms. The correlation between subclinical hypothyroidism and some of cardiovascular disease risk factors such as serum lipids, homocysteine levels and also insulin resistance index is not well established and the current study was conducted to clarify this issue. Seventy four patients with mild elevation in levels of thyroid stimulating hormone (TSH) along with normal levels of T3 and T4 were selected as patients group and 74 age and sex matched individuals were selected as healthy control group. Serum insulin, triglyceride, glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol and homocysteine levels were measured. Obtained data compared between groups with independent sample t-test. For evaluation of the correlation between mentioned parameters Pearson correlation coefficient method was used. Serum levels of LDL-C and total cholesterol significantly increased in SCH group compared to healthy control group. Homeostatic Model Assessment of Insulin Resistance (HOM-IR) and serum homocysteine level significantly elevated in patients with SCH compared to control group. There was a significant direct correlation between HOM-IR and serum homocysteine levels in SCH patients. Subclinical hypothyroidism likely have significant effect on insulin resistance as major diabetes risk factors and also cardiovascular disease risk factors such as homocysteine. The direct correlation between HOM-IR with serum homocysteine level indicate the possible role of insulin resistance in elevation of serum homocysteine in SCH patient group. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Hepatocyte growth factor is elevated in amniotic fluid from obese women and regulates placental glucose and fatty acid metabolism.

PubMed

Visiedo, F; Bugatto, F; Carrasco-Fernández, C; Sáez-Benito, A; Mateos, R M; Cózar-Castellano, I; Bartha, J L; Perdomo, G

2015-04-01

To evaluate the impact of the pro-inflammatory cytokine hepatocyte growth factor (HGF) on the regulation of glucose and lipid placental metabolism. HGF levels were quantified in amniotic fluid and placenta from control and obese women. 2-deoxy-glucose (2-DOG) uptake, glycolysis, fatty acid oxidation (FAO), fatty acid esterification, de novo fatty acid synthesis, triglyceride levels and carnitine palmitoyltransferase activities (CPT) were measured in placental explants upon addition of pathophysiological HGF levels. In obese women, total- and -activated-HGF levels in amniotic fluid were elevated ∼24%, and placental HGF levels were ∼3-fold higher than in control women. At a similar dose to that present in amniotic fluid of obese women, HGF (30 ng/mL) increased Glut-1 levels and 2-DOG uptake by ∼25-30% in placental explants. HGF-mediated effect on 2-DOG uptake was dependent on the activation of phosphatidylinositol 3-kinase signaling pathway. In addition, HGF decreased ∼20% FAO, whereas esterification and de novo fatty acid synthesis increased ∼15% and ∼25% respectively, leading to 2-fold triglyceride accumulation in placental explants. In parallel, HGF reduced CPT-I activity ∼70%. HGF is a cytokine elevated in amniotic fluid and placental tissue of obese women, which through its ability to stimulate 2-DOG uptake and metabolism impairs FAO and enhances esterification and de novo fatty acid synthesis, leading to accumulation of placental triglycerides. Copyright © 2015 Elsevier Ltd. All rights reserved.

Elevated free nitrotyrosine levels, but not protein-bound nitrotyrosine or hydroxyl radicals, throughout amyotrophic lateral sclerosis (ALS)-like disease implicate tyrosine nitration as an aberrant in vivo property of one familial ALS-linked superoxide dismutase 1 mutant.

PubMed

Bruijn, L I; Beal, M F; Becher, M W; Schulz, J B; Wong, P C; Price, D L; Cleveland, D W

1997-07-08

Mutations in superoxide dismutase 1 (SOD1; EC 1.15.1.1) are responsible for a proportion of familial amyotrophic lateral sclerosis (ALS) through acquisition of an as-yet-unidentified toxic property or properties. Two proposed possibilities are that toxicity may arise from imperfectly folded mutant SOD1 catalyzing the nitration of tyrosines [Beckman, J. S., Carson, M., Smith, C. D. & Koppenol, W. H. (1993) Nature (London) 364, 584] through use of peroxynitrite or from peroxidation arising from elevated production of hydroxyl radicals through use of hydrogen peroxide as a substrate [Wiedau-Pazos, M., Goto, J. J., Rabizadeh, S., Gralla, E. D., Roe, J. A., Valentine, J. S. & Bredesen, D. E. (1996) Science 271, 515-518]. To test these possibilities, levels of nitrotyrosine and markers for hydroxyl radical formation were measured in two lines of transgenic mice that develop progressive motor neuron disease from expressing human familial ALS-linked SOD1 mutation G37R. Relative to normal mice or mice expressing high levels of wild-type human SOD1, 3-nitrotyrosine levels were elevated by 2- to 3-fold in spinal cords coincident with the earliest pathological abnormalities and remained elevated in spinal cord throughout progression of disease. However, no increases in protein-bound nitrotyrosine were found during any stage of SOD1-mutant-mediated disease in mice or at end stage of sporadic or SOD1-mediated familial human ALS. When salicylate trapping of hydroxyl radicals and measurement of levels of malondialdehyde were used, there was no evidence throughout disease progression in mice for enhanced production of hydroxyl radicals or lipid peroxidation, respectively. The presence of elevated nitrotyrosine levels beginning at the earliest stages of cellular pathology and continuing throughout progression of disease demonstrates that tyrosine nitration is one in vivo aberrant property of this ALS-linked SOD1 mutant.

Elevated pCO2 affects tissue biomass composition, but not calcification, in a reef coral under two light regimes.

PubMed

Wall, C B; Mason, R A B; Ellis, W R; Cunning, R; Gates, R D

2017-11-01

Ocean acidification (OA) is predicted to reduce reef coral calcification rates and threaten the long-term growth of coral reefs under climate change. Reduced coral growth at elevated p CO 2 may be buffered by sufficiently high irradiances; however, the interactive effects of OA and irradiance on other fundamental aspects of coral physiology, such as the composition and energetics of coral biomass, remain largely unexplored. This study tested the effects of two light treatments (7.5 versus 15.7 mol photons m -2  d -1 ) at ambient or elevated p CO 2 (435 versus 957 µatm) on calcification, photopigment and symbiont densities, biomass reserves (lipids, carbohydrates, proteins), and biomass energy content (kJ) of the reef coral Pocillopora acuta from Kāne'ohe Bay, Hawai'i. While p CO 2 and light had no effect on either area- or biomass-normalized calcification, tissue lipids gdw -1 and kJ gdw -1 were reduced 15% and 14% at high p CO 2 , and carbohydrate content increased 15% under high light. The combination of high light and high p CO 2 reduced protein biomass (per unit area) by approximately 20%. Thus, under ecologically relevant irradiances, P. acuta in Kāne'ohe Bay does not exhibit OA-driven reductions in calcification reported for other corals; however, reductions in tissue lipids, energy content and protein biomass suggest OA induced an energetic deficit and compensatory catabolism of tissue biomass. The null effects of OA on calcification at two irradiances support a growing body of work concluding some reef corals may be able to employ compensatory physiological mechanisms that maintain present-day levels of calcification under OA. However, negative effects of OA on P. acuta biomass composition and energy content may impact the long-term performance and scope for growth of this species in a high p CO 2 world.

Elevated pCO2 affects tissue biomass composition, but not calcification, in a reef coral under two light regimes

PubMed Central

Mason, R. A. B.; Ellis, W. R.; Cunning, R.; Gates, R. D.

2017-01-01

Ocean acidification (OA) is predicted to reduce reef coral calcification rates and threaten the long-term growth of coral reefs under climate change. Reduced coral growth at elevated pCO2 may be buffered by sufficiently high irradiances; however, the interactive effects of OA and irradiance on other fundamental aspects of coral physiology, such as the composition and energetics of coral biomass, remain largely unexplored. This study tested the effects of two light treatments (7.5 versus 15.7 mol photons m−2 d−1) at ambient or elevated pCO2 (435 versus 957 µatm) on calcification, photopigment and symbiont densities, biomass reserves (lipids, carbohydrates, proteins), and biomass energy content (kJ) of the reef coral Pocillopora acuta from Kāne‘ohe Bay, Hawai‘i. While pCO2 and light had no effect on either area- or biomass-normalized calcification, tissue lipids gdw−1 and kJ gdw−1 were reduced 15% and 14% at high pCO2, and carbohydrate content increased 15% under high light. The combination of high light and high pCO2 reduced protein biomass (per unit area) by approximately 20%. Thus, under ecologically relevant irradiances, P. acuta in Kāne‘ohe Bay does not exhibit OA-driven reductions in calcification reported for other corals; however, reductions in tissue lipids, energy content and protein biomass suggest OA induced an energetic deficit and compensatory catabolism of tissue biomass. The null effects of OA on calcification at two irradiances support a growing body of work concluding some reef corals may be able to employ compensatory physiological mechanisms that maintain present-day levels of calcification under OA. However, negative effects of OA on P. acuta biomass composition and energy content may impact the long-term performance and scope for growth of this species in a high pCO2 world. PMID:29291059

Protective Role of Spirulina platensis against Acute Deltamethrin-Induced Toxicity in Rats

PubMed Central

Abdel-Daim, Mohamed M.; Abuzead, Said M. M.; Halawa, Safaa M.

2013-01-01

Deltamethrin is a broad-spectrum synthetic pyrethroid insecticide and acaricide widely used for agricultural and veterinary purposes. However, its human and animal exposure leads to hepatonephrotoxicity. Therefore, the present study was undertaken to examine the hepatonephroprotective and antioxidant potential of Spirulina platensis against deltamethrin toxicity in male Wistar albino rats. Deltamethrin treated animals revealed a significant increase in serum biochemical parameters as well as hepatic and renal lipid peroxidation but caused an inhibition in antioxidant biomarkers. Spirulina normalized the elevated serum levels of AST, ALT, APL, uric acid, urea and creatinine. Furthermore, it reduced deltamethrin-induced lipid peroxidation and oxidative stress in a dose dependent manner. Therefore, it could be concluded that spirulina administration able to minimize the toxic effects of deltamethrin by its free radical-scavenging and potent antioxidant activity. PMID:24039839

Influence of increasing temperature and salinity on herbicide toxicity in estuarine phytoplankton.

PubMed

DeLorenzo, Marie E; Danese, Loren E; Baird, Thomas D

2013-07-01

Ecological risk assessments are, in part, based on results of toxicity tests conducted under standard exposure conditions. Global climate change will have a wide range of effects on estuarine habitats, including potentially increasing water temperature and salinity, which may alter the risk assessment of estuarine pollutants. We examined the effects of increasing temperature and salinity on the toxicity of common herbicides (irgarol, diuron, atrazine, and ametryn) to the phytoplankton species Dunaliella tertiolecta. Static 96-h algal bioassays were conducted for each herbicide under four exposure scenarios: standard temperature and salinity (25°C, 20 ppt), standard temperature and elevated salinity (25°C, 40 ppt), elevated temperature and standard salinity (35°C, 20 ppt), and elevated temperature and elevated salinity (35°C, 40 ppt). The endpoints assessed were algal cell density at 96 h, growth rate, chlorophyll a content, lipid content, and starch content. Increasing exposure temperature reduced growth rate and 96-h cell density but increased the cellular chlorophyll and lipid concentrations of the control algae. Exposure condition did not alter starch content of control algae. Herbicides were found to decrease growth rate, 96 h cell density, and cellular chlorophyll and lipid concentrations, while starch concentrations increased with herbicide exposure. Herbicide effects under standard test conditions were then compared with those observed under elevated temperature and salinity. Herbicide effects on growth rate, cell density, and starch content were more pronounced under elevated salinity and temperature conditions. To encompass the natural variability in estuarine temperature and salinity, and to account for future changes in climate, toxicity tests should be conducted under a wider range of environmental conditions. Copyright © 2011 Wiley Periodicals, Inc.

Endothelin-1 Expression Associated with Lipid Peroxidation and Nuclear Factor-κB Activation in Type 2 Diabetes Mellitus Patients with Angiopathy and Limb Amputation.

PubMed

Kuo, Yur-Ren; Chien, Ching-Ming; Kuo, Ming-Jen; Wang, Feng-Sheng; Huang, Eng-Yen; Wang, Ching-Jen

2016-01-01

It is unclear whether diabetic angiopathy is related to oxidative stress-associated endothelial dysfunction. The authors investigated whether alteration of endothelin-1 and lipid peroxide production and activation of nuclear factor-κB expression were involved in lower limb amputation in type 2 diabetes mellitus patients. A total of 135 subjects including 51 type 2 diabetes mellitus patients with major lower extremity amputations and 36 diabetes mellitus patients without limb and vascular complication and 48 normal controls were recruited for this study. The authors measured the plasma soluble endothelin-1 concentrations by a sandwich enzyme immunoassay, and measured oxidative stress as determined by the lipid peroxide byproduct malondialdehyde. Histologic staining and nuclear factor-κB activation determined by electrophoretic mobility shift assay of the amputated vessels were examined. Histologic staining revealed that severe arteriosclerosis with atheroma formation in the amputated diabetic arteries was significantly prominent compared with normal controls. Soluble endothelin-1 concentrations and malondialdehyde levels were increased significantly in diabetic amputation patients compared with other groups (p < 0.001). The nuclear factor-κB binding activity in amputated diabetic stump vessels was more prominent compared with healthy vessels without diabetes mellitus. There was a positive correlation between endothelin-1 and malondialdehyde in patients with diabetic amputation (r = 0.46, p = 0.001). These results suggest that elevation of endothelin-1 and lipid peroxide levels is involved in the pathogenesis of diabetic foot amputation. An increase of lipid peroxide and endothelin-1 associated with nuclear factor-κB activation plays an important role in the development of diabetic angiopathies.

Application of GC/MS-based metabonomic profiling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats

PubMed Central

Zhang, Qi; Wang, Guang-ji; A, Ji-ye; Wu, Di; Zhu, Ling-ling; Ma, Bo; Du, Yu

2009-01-01

Aim: To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia. Methods: EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA). Results: The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and –treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and–treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB. Conclusion: EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia. PMID:19960012

Application of GC/MS-based metabonomic profiling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats.

PubMed

Zhang, Qi; Wang, Guang-ji; A, Ji-ye; Wu, Di; Zhu, Ling-ling; Ma, Bo; Du, Yu

2009-12-01

To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia. EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA). The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and -treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and-treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB. EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia.

Incremental replacement of saturated fats by n-3 fatty acids in high-fat, high-cholesterol diets reduces elevated plasma lipid levels and arterial lipoprotein lipase, macrophages and atherosclerosis in LDLR-/- mice.

PubMed

Chang, Chuchun L; Torrejon, Claudia; Jung, Un Ju; Graf, Kristin; Deckelbaum, Richard J

2014-06-01

Effects of progressive substitution of dietary n-3 fatty acids (FA) for saturated FA (SAT) on modulating risk factors for atherosclerosis have not been fully defined. Our previous reports demonstrate that SAT increased, but n-3 FA decreased, arterial lipoprotein lipase (LpL) levels and arterial LDL-cholesterol deposition early in atherogenesis. We now questioned whether incremental increases in dietary n-3 FA can counteract SAT-induced pro-atherogenic effects in atherosclerosis-prone LDL-receptor knockout (LDLR-/-) mice and have identified contributing mechanisms. Mice were fed chow or high-fat diets enriched in SAT, n-3, or a combination of both SAT and n-3 in ratios of 3:1 (S:n-3 3:1) or 1:1 (S:n-3 1:1). Each diet resulted in the expected changes in fatty acid composition in blood and aorta for each feeding group. SAT-fed mice became hyperlipidemic. By contrast, n-3 inclusion decreased plasma lipid levels, especially cholesterol. Arterial LpL and macrophage levels were increased over 2-fold in SAT-fed mice but these were decreased with incremental replacement with n-3 FA. n-3 FA partial inclusion markedly decreased expression of pro-inflammatory markers (CD68, IL-6, and VCAM-1) in aorta. SAT diets accelerated advanced atherosclerotic lesion development, whereas all n-3 FA-containing diets markedly slowed atherosclerotic progression. Mechanisms whereby dietary n-3 FA may improve adverse cardiovascular effects of high-SAT, high-fat diets include improving plasma lipid profiles, increasing amounts of n-3 FA in plasma and the arterial wall. Even low levels of replacement of SAT by n-3 FA effectively reduce arterial lipid deposition by decreasing aortic LpL, macrophages and pro-inflammatory markers. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

LipiD-QuanT: a novel method to quantify lipid accumulation in live cells.

PubMed

Varinli, Hilal; Osmond-McLeod, Megan J; Molloy, Peter L; Vallotton, Pascal

2015-11-01

Lipid droplets (LDs) are the main storage organelles for triglycerides. Elucidation of lipid accumulation mechanisms and metabolism are essential to understand obesity and associated diseases. Adipogenesis has been well studied in murine 3T3-L1 and human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell lines. However, most techniques for measuring LD accumulation are either not quantitative or can be destructive to samples. Here, we describe a novel, label-free LD quantification technique (LipiD-QuanT) to monitor lipid dynamics based on automated image analysis of phase contrast microscopy images acquired during in vitro human adipogenesis. We have applied LipiD-QuanT to measure LD accumulation during differentiation of SGBS cells. We demonstrate that LipiD-QuanT is a robust, nondestructive, time- and cost-effective method compared with other triglyceride accumulation assays based on enzymatic digest or lipophilic staining. Further, we applied LipiD-QuanT to measure the effect of four potential pro- or antiobesogenic substances: DHA, rosiglitazone, elevated levels of D-glucose, and zinc oxide nanoparticles. Our results revealed that 2 µmol/l rosiglitazone treatment during adipogenesis reduced lipid production and caused a negative shift in LD diameter size distribution, but the other treatments showed no effect under the conditions used here. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Metabolic Analysis of Adaptation to Short-Term Changes in Culture Conditions of the Marine Diatom Thalassiosira pseudonana

PubMed Central

Bromke, Mariusz A.; Giavalisco, Patrick; Willmitzer, Lothar; Hesse, Holger

2013-01-01

This report describes the metabolic and lipidomic profiling of 97 low-molecular weight compounds from the primary metabolism and 124 lipid compounds of the diatom Thalassiosira pseudonana. The metabolic profiles were created for diatoms perturbed for 24 hours with four different treatments: (I) removal of nitrogen, (II) lower iron concentration, (III) addition of sea salt, (IV) addition of carbonate to their growth media. Our results show that as early as 24 hours after nitrogen depletion significant qualitative and quantitative change in lipid composition as well as in the primary metabolism of Thalassiosira pseudonana occurs. So we can observe the accumulation of several storage lipids, namely triacylglycerides, and TCA cycle intermediates, of which citric acid increases more than 10-fold. These changes are positively correlated with expression of TCA enzymes genes. Next to the TCA cycle intermediates and storage lipid changes, we have observed decrease in N-containing lipids and primary metabolites such as amino acids. As a measure of counteracting nitrogen starvation, we have observed elevated expression levels of nitrogen uptake and amino acid biosynthetic genes. This indicates that diatoms can fast and efficiently adapt to changing environment by altering the metabolic fluxes and metabolite abundances. Especially, the accumulation of proline and the decrease of dimethylsulfoniopropionate suggest that the proline is the main osmoprotectant for the diatom in nitrogen rich conditions. PMID:23799147

Serum lipid alterations in GBA-associated Parkinson's disease.

PubMed

Guedes, Leonor Correia; Chan, Robin Barry; Gomes, Marcos António; Conceição, Vasco A; Machado, Raquel Bouça; Soares, Tiago; Xu, Yimeng; Gaspar, Paulo; Carriço, Joao André; Alcalay, Roy N; Ferreira, Joaquim J; Outeiro, Tiago Fleming; Miltenberger-Miltenyi, Gabriel

2017-11-01

Mutations in the GBA gene, encoding for the lysosomal enzyme glucocerebrosidase, are associated with Gaucher disease. Alterations in plasma sphingolipids have been reported in Gaucher, and similarly in brain extracts in Lewy body disease. As GBA mutations are prevalent risk factors for Parkinson's disease and overlap of molecular pathways are presumable, here we assessed the lipid profiles in Parkinson's patients with and without GBA mutations. We sequenced all GBA exons in 415 Parkinson's patients, previously genotyped for LRRK2. 64 patients (29 GBA positive vs. 35 non-GBA-carriers including 18 LRRK2 positive and 17 non-mutated) were analyzed for chitotriosidase activity and for the concentration of 40 lipid classes using HPLC-MS. 29/415 patients (6.9%) carried 8 different GBA mutations associated with Gaucher or Parkinson's, including one novel mutation. Chitotriosidase activity was similar across the genetic groups, while the levels of key lipids were altered in GBA mutation carriers: Monohexosylceramide, Ceramide and Sphingomyelin were elevated; while Phosphatidic acid (PA), Phosphatidylethanolamine (PE), Plasmalogen phosphatidylethanolamine (PEp) and Acyl Phosphatidylglycerol (AcylPG) were decreased. The results suggest an important role for these lipids in GBA mediated Parkinson's disease and assist in the identification of common pathways between Gaucher and Parkinson's. Ultimately, our findings may lead to the identification of novel biomarkers for individuals at increased risk of developing Parkinson's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of glycemic control upon serum lipids and lipid transfers to HDL in patients with type 2 diabetes mellitus: novel findings in unesterified cholesterol status.

PubMed

Laverdy, O G; Hueb, W A; Sprandel, M C O; Kalil-Filho, R; Maranhão, R C

2015-04-01

Investigate the relations of glycemic levels with plasma lipids and in vitro lipid transfers to HDL in patients with type 2 diabetes mellitus. 143 patients with type 2 diabetes not taking anti-lipidemic drugs were separated into 2 groups: group A included 62 patients with glycated hemoglobin (HbA₁c)≤6.5% (48 mmol/mol) and group B 81 patients with HbA₁c>6.5%. In vitro transfer of lipids was determined by 1 h incubation of a donor nanoemulsion containing radioactively labeled unesterified and esterified cholesterol, phospholipids and triglycerides with whole plasma followed by chemical precipitation and radioactive counting in the supernatant (HDL). LDL and HDL cholesterol were similar in Group A and B, but group B had higher triglycerides (2.31±1.30 vs. 1.58±0.61 mmol/l, P<0.0001) and total and non-HDL unesterified cholesterol (36.3±7.8 vs. 33.9±5.9 mmol/l, P<0,05; 30.6±7.9 vs. 27.6±6.2 mmol/l, P<0,05; respectively) than group A and a non-significant trend to increased apolipoprotein B (103±20 vs. 97±20 mg/dl, P=0.08). 36 patients with the highest, ≥8.0% (64 mmol/mol), HbA₁c also showed non-significant trend of elevated non-esterified fatty acids (NEFA) compared to 37 with lowest, ≤6.0% (42 mmol/mol), HbA₁c (P=0.08). Patients with higher NEFA had higher triglycerides than those with lower NEFA levels (P<0.01).Transfers of all lipids from nanoemulsion to HDL and lipid composition of HDL were equal in both groups. For the first time it was shown that in addition to triglycerides, unesterified cholesterol is also a marker of poor glycemic control. In vitro HDL lipid transfers, an important aspect of HDL metabolism, were not related with the glycemic control. © Georg Thieme Verlag KG Stuttgart · New York.

Defective macroautophagic turnover of brain lipids in the TgCRND8 Alzheimer mouse model: prevention by correcting lysosomal proteolytic deficits.

PubMed

Yang, Dun-Sheng; Stavrides, Philip; Saito, Mitsuo; Kumar, Asok; Rodriguez-Navarro, Jose A; Pawlik, Monika; Huo, Chunfeng; Walkley, Steven U; Saito, Mariko; Cuervo, Ana M; Nixon, Ralph A

2014-12-01

Autophagy, the major lysosomal pathway for the turnover of intracellular organelles is markedly impaired in neurons in Alzheimer's disease and Alzheimer mouse models. We have previously reported that severe lysosomal and amyloid neuropathology and associated cognitive deficits in the TgCRND8 Alzheimer mouse model can be ameliorated by restoring lysosomal proteolytic capacity and autophagy flux via genetic deletion of the lysosomal protease inhibitor, cystatin B. Here we present evidence that macroautophagy is a significant pathway for lipid turnover, which is defective in TgCRND8 brain where lipids accumulate as membranous structures and lipid droplets within giant neuronal autolysosomes. Levels of multiple lipid species including several sphingolipids (ceramide, ganglioside GM3, GM2, GM1, GD3 and GD1a), cardiolipin, cholesterol and cholesteryl esters are elevated in autophagic vacuole fractions and lysosomes isolated from TgCRND8 brain. Lipids are localized in autophagosomes and autolysosomes by double immunofluorescence analyses in wild-type mice and colocalization is increased in TgCRND8 mice where abnormally abundant GM2 ganglioside-positive granules are detected in neuronal lysosomes. Cystatin B deletion in TgCRND8 significantly reduces the number of GM2-positive granules and lowers the levels of GM2 and GM3 in lysosomes, decreases lipofuscin-related autofluorescence, and eliminates giant lipid-containing autolysosomes while increasing numbers of normal-sized autolysosomes/lysosomes with reduced content of undigested components. These findings have identified macroautophagy as a previously unappreciated route for delivering membrane lipids to lysosomes for turnover, a function that has so far been considered to be mediated exclusively through the endocytic pathway, and revealed that autophagic-lysosomal dysfunction in TgCRND8 brain impedes lysosomal turnover of lipids as well as proteins. The amelioration of lipid accumulation in TgCRND8 by removing cystatin B inhibition on lysosomal proteases suggests that enhancing lysosomal proteolysis improves the overall environment of the lysosome and its clearance functions, which may be possibly relevant to a broader range of lysosomal disorders beyond Alzheimer's disease. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Screening and advanced lipid phenotyping in familial hypercholesterolemia: The Very Large Database of Lipids Study-17 (VLDL-17).

PubMed

Miller, P Elliott; Martin, Seth S; Toth, Peter P; Santos, Raul D; Blaha, Michael J; Nasir, Khurram; Virani, Salim S; Post, Wendy S; Blumenthal, Roger S; Jones, Steven R

2015-01-01

Familial hypercholesterolemia (FH) is an autosomal dominant dyslipidemia characterized by defective low-density lipoprotein (LDL) clearance. The aim of this study was to compare Friedewald-estimated LDL cholesterol (LDL-C) to biologic LDL-C in individuals screening positive for FH and then further characterize FH phenotypes. We studied 1,320,581 individuals from the Very Large Database of Lipids, referred from 2009 to 2011 for Vertical Auto Profile ultracentrifugation testing. Friedewald LDL-C was defined as the cholesterol content of LDL-C, intermediate-density lipoprotein cholesterol, and lipoprotein(a) cholesterol (Lp(a)-C), with LDL-C representing biologic LDL-C. Using Friedewald LDL-C, we phenotypically categorized patients by the National Lipid Association guideline age-based screening thresholds for FH. In those meeting criteria, we categorized patients using population percentile-equivalent biologic LDL-C cutpoints and explored Lp(a)-C and remnant lipoprotein cholesterol (RLP-C) levels. Overall, 3829 patients met phenotypic criteria for FH by Friedewald LDL-C screening (FH+). Of those screening FH+, 78.8% were above and 21.2% were below the population percentile-equivalent biologic LDL-C. The mean difference in Friedewald biologic LDL-C percentiles was -0.01 (standard deviation, 0.17) for those above, and 1.92 (standard deviation, 9.16) for those below, respectively. Over 1 of 3 were found to have an elevated Lp(a)-C and over 50% had RLP-C greater than 95th percentile of the entire VLDL population. Of those who screened FH+, Friedewald and biologic LDL-C levels were closely correlated. Large proportions of the FH+ group had excess levels of Lp(a)-C and RLP-C. Future studies are warranted to study these mixed phenotypic groups and determine the role for further risk stratification and treatment algorithms. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Yansong; Xu, Dan; Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071

The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR andmore » immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine ingestion induced GC metabolic activation in IUGR fetal rats.« less

Elevated expression of glutathione peroxidase in PC12 cells results in protection against methamphetamine but not MPTP toxicity.

PubMed

Hom, D G; Jiang, D; Hong, E J; Mo, J Q; Andersen, J K

1997-06-01

In vivo administration of either 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or methamphetamine (MA) produces damage to the dopaminergic nervous system which may be due in part to the generation of reactive oxygen species (ROS). The resistance of superoxide dismutase (SOD) over-expressing transgenic mice to the effects of both MPTP and MA suggests the involvement of superoxide in the resulting neurotoxicity of both compounds. Superoxide can be converted by SOD to hydrogen peroxide, which itself can cause cellular degeneration by reacting with free iron to produce highly reactive hydroxyl radicals resulting in damage to proteins, nucleic acids and membrane phospholipids. Hydrogen peroxide has also been reported to be produced via inhibition of NADH dehydrogenase by MPP + formed during oxidation of MPTP by MAO-B and by dopamine auto-oxidation following MA-induced dopamine release from synaptic vesicles within nerve terminals. To test whether hydrogen peroxide is an important factor in the toxicity of either of these two neurotoxins, we created clonal PC12 lines expressing elevated levels of the hydrogen peroxide-reducing enzyme glutathione peroxidase (GSHPx). Elevation of GSHPx levels in PC12 was found to diminish the rise in ROS levels and lipid peroxidation resulting from MA but not MPTP treatment. Elevated levels of GSHPx also appeared to prevent decreases in transport-mediated dopamine uptake produced via MA administration as well as to attenuate toxin-induced cell loss as measured by either MTT reduction or LDH release. Our data, therefore, suggest that hydrogen peroxide production likely contributes to MA toxicity in dopaminergic neurons.

Lipidomic profiling reveals protective function of fatty acid oxidation in cocaine-induced hepatotoxicity[S

PubMed Central

Shi, Xiaolei; Yao, Dan; Gosnell, Blake A.; Chen, Chi

2012-01-01

During cocaine-induced hepatotoxicity, lipid accumulation occurs prior to necrotic cell death in the liver. However, the exact influences of cocaine on the homeostasis of lipid metabolism remain largely unknown. In this study, the progression of subacute hepatotoxicity, including centrilobular necrosis in the liver and elevation of transaminase activity in serum, was observed in a three-day cocaine treatment, accompanying the disruption of triacylglycerol (TAG) turnover. Serum TAG level increased on day 1 of cocaine treatment but remained unchanged afterwards. In contrast, hepatic TAG level was elevated continuously during three days of cocaine treatment and was better correlated with the development of hepatotoxicity. Lipidomic analyses of serum and liver samples revealed time-dependent separation of the control and cocaine-treated mice in multivariate models, which was due to the accumulation of long-chain acylcarnitines together with the disturbances of many bioactive phospholipid species in the cocaine-treated mice. An in vitro function assay confirmed the progressive inhibition of mitochondrial fatty acid oxidation after the cocaine treatment. Cotreatment of fenofibrate significantly increased the expression of peroxisome proliferator-activated receptor α (PPARα)-targeted genes and the mitochondrial fatty acid oxidation activity in the cocaine-treated mice, resulting in the inhibition of cocaine-induced acylcarnitine accumulation and other hepatotoxic effects. Overall, the results from this lipidomics-guided study revealed that the inhibition of fatty acid oxidation plays an important role in cocaine-induced liver injury. PMID:22904346

Metabolic and cardiovascular impact of oral contraceptives in polycystic ovary syndrome.

PubMed

Soares, G M; Vieira, C S; de Paula Martins, W; Dos Reis, R M; de Sá, M F S; Ferriani, R A

2009-01-01

Chronic anovulation, polycystic ovarian morphology and hyperandrogenism are the diagnostic criteria for polycystic ovary syndrome (PCOS). Metabolic disturbances are more common in PCOS women who are prone to develop metabolic syndrome and to present higher levels of some cardiovascular disease risk marker. Oral contraceptives are widely used in PCOS, but conflicting data have been reported regarding their impact on carbohydrate and lipid metabolism on PCOS women. This paper presents a critical evaluation of combined oral contraceptives (COCs) metabolic effect - carbohydrate metabolism and insulin sensitivity, lipid metabolism, haemostasis, body weight, arterial pressure and cardiovascular impact - on PCOS women. Because of the paucity of data on the impact of COCs on cardiovascular and metabolic parameters in PCOS patients, most of there commendations are based on studies involving ovulatory women. The use of low-dose COCs is preferable in PCOS, especially among patients with glucose intolerance, insulin resistance and uncomplicated diabetes mellitus. Although reported as a side effect of COCs, marked weight gain has not been confirmed among users. However, when arterial hypertension or elevated risk for thromboembolism is present, progestogen-only hormonal contraceptives should be used instead of COCs. Regarding dyslipidaemia, COCs reduce low-density lipoprotein and total cholesterol and elevate high-density lipoprotein and triglycerides, and therefore are not recommended for women with high triglycerides levels. The choice of a COC, which alleviates the PCOS-induced hyperandrogenism without significant negative impact on cardiovascular risk, is one of the greatest challenges faced by gynaecologists nowadays.

Transgenic Wuzhishan minipigs designed to express a dominant-negative porcine growth hormone receptor display small stature and a perturbed insulin/IGF-1 pathway.

PubMed

Li, Feida; Li, Yong; Liu, Huan; Zhang, Xingju; Liu, Chuxin; Tian, Kai; Bolund, Lars; Dou, Hongwei; Yang, Wenxian; Yang, Huanming; Staunstrup, Nicklas Heine; Du, Yutao

2015-12-01

Growth hormone (GH) is an anabolic mitogen with widespread influence on cellular growth and differentiation as well as on glucose and lipid metabolism. GH binding to the growth hormone receptor (GHR) on hepatocytes prompts expression of insulin growth factor I (IGF-1) involved in nutritionally induced compensatory hyperplasia of pancreatic β-cell islets and insulin release. A prolonged hyperactivity of the IGF-1/insulin axis in the face of insulinotropic nutrition, on the other hand, can lead to collapse of the pancreatic islets and glucose intolerance. Individuals with Laron syndrome carry mutations in the GHR gene resulting in severe congenital IGF-1 deficiency and elevated GH serum levels leading to short stature as well as perturbed lipid and glucose metabolism. However, these individuals enjoy a reduced prevalence of acne, cancer and possibly diabetes. Minipigs have become important biomedical models for human conditions due to similarities in organ anatomy, physiology, and metabolism relative to humans. The purpose of this study was to generate transgenic Wuzhishan minipigs by handmade cloning with impaired systemic GHR activity and assess their growth profile and glucose metabolism. Transgenic minipigs featuring overexpression of a dominant-negative porcine GHR (GHR(dm)) presented postnatal growth retardation and proportionate dwarfism. Molecular changes included elevated GH serum levels and mild hyperglycemia. We believe that this model may prove valuable in the study of GH functions in relation to cancer, diabetes and longevity.

Chromium (d-Phenylalanine)3 Alleviates High Fat-Induced Insulin Resistance and Lipid Abnormalities

PubMed Central

Kandadi, Machender Reddy; Unnikrishnan, MK; Warrier, Ajaya Kumar Sankara; Du, Min; Ren, Jun; Sreejayan, Nair

2010-01-01

High-fat diet has been implicated as a major cause of insulin resistance and dyslipidemia. The objective of this study was to evaluate the impact of dietary-supplementation of chromium (d-phenylalanine)3 [Cr(d-Phe)3] on -glucose and -insulin tolerance in high-fat diet fed mice. C57BL/6-mice were randomly assigned to orally receive vehicle or Cr(d-Phe)3 (45 μg of elemental chromium/kg/day) for 8-weeks. High-fat-fed mice exhibited impaired whole-body -glucose and- insulin tolerance and elevated serum triglyceride levels compared to normal chow-fed mice. Insulin-stimulated glucose up- take in the gastrocnemius muscles, assessed as 2-[3H-deoxyglucose] incorporation was markedly diminished in high-fat fed mice compared to control mice. Treatment with chromium reconciled the high-fat diet-induced alterations in carbohydrate and lipid metabolism. Treatment of cultured, differentiated myotubes with palmitic acid evoked insulin resistance as evidenced by lower levels of insulin-stimulated Akt-phosphorylation, elevated JNK-phosphorylation, (assessed by Western blotting), attenuation of phosphoinositol-3-kinase activity (determined in the insulin-receptor substrate-1-immunoprecipitates by measuring the extent of phosphorylation of phosphatidylinositol by γ-32P-ATP), and impairment in cellular glucose up-take, all of which were inhibited by Cr(d-Phe)3. These results suggest a beneficial effect of chromium-supplementation in insulin resistant conditions. It is likely that these effects of chromium may be mediated by augmenting downstream insulin signaling. PMID:21134603

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study

PubMed Central

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-01-01

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394–0.708), and eGFR (β = −0.481; 95%CI, −0.731–−0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11–1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study.

PubMed

Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

2015-07-16

Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394-0.708), and eGFR (β = -0.481; 95%CI, -0.731--0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11-1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism.

Plasma oxalic acid and calcium levels in oxalate poisoning

PubMed Central

Zarembski, P. M.; Hodgkinson, A.

1967-01-01

Observations are reported on five cases of suicide or attempted suicide by poisoning with oxalic acid or ethylene glycol. Elevated oxalic acid levels were observed in the plasma, stomach contents, and a number of tissues. Raised oxalic acid levels in plasma were associated with reduced total and ultrafilterable calcium levels. It is suggested that the reduction in plasma total calcium level is due mainly to the deposition of calcium oxalate in the soft tissues, but inhibition of the parathyroid glands may be a contributory factor. Microscopic examination of various tissues indicated that oxalic acid is deposited in the tissues in two forms: (1) crystalline calcium oxalate dihydrate in the kidney and (2) a non-crystalline complex of calcium oxalate and lipid in liver and other tissues. PMID:5602563

Assessment of oxidative stress markers and concentrations of selected elements in the leaves of Cassia occidentalis growing wild on a coal fly ash basin.

PubMed

Love, Amit; Banerjee, B D; Babu, C R

2013-08-01

Assessment of oxidative stress levels and tissue concentrations of elements in plants growing wild on fly ash basins is critical for realistic hazard identification of fly ash disposal areas. Hitherto, levels of oxidative stress markers in plants growing wild on fly ash basins have not been adequately investigated. We report here concentrations of selected metal and metalloid elements and levels of oxidative stress markers in leaves of Cassia occidentalis growing wild on a fly ash basin (Badarpur Thermal Power Station site) and a reference site (Garhi Mandu Van site). Plants growing on the fly ash basin had significantly high foliar concentration of As, Ni, Pb and Se and low foliar concentration of Mn and Fe compared to the plants growing on the reference site. The plants inhabiting the fly ash basin showed signs of oxidative stress and had elevated levels of lipid peroxidation, electrolyte leakage from cells and low levels of chlorophyll a and total carotenoids compared to plants growing at the reference site. The levels of both protein thiols and nonprotein thiols were elevated in plants growing on the fly ash basin compared to plants growing on the reference site. However, no differences were observed in the levels of cysteine, reduced glutathione and oxidized glutathione in plants growing at both the sites. Our study suggests that: (1) fly ash triggers oxidative stress responses in plants growing wild on fly ash basin, and (2) elevated levels of protein thiols and nonprotein thiols may have a role in protecting the plants from environmental stress.

Effects of melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism.

PubMed

Baydas, Burhanettin; Meral, Ismail

2005-07-01

1. The present study was designed to investigate the effects of high-dose melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism. 2. Twenty-four albino male rats, weighing 240-260 g, were randomly allotted into one of three experimental groups (control, hyperthyroid and hyperthyroid + melatonin treatment), with each group containing eight animals. Hyperthyroidism was induced by a daily with i.p. injection of 200 microg l-thyroxine for 30 days. In addition to l-thyroxin treatment, rats in the hyperthyroid + melatonin treatment group were also given daily i.p. injections of 10 mg/kg melatonin on the last 10 days of l-thyroxine treatment. Control animals received injections of an equivalent volume of saline solution. Rats received the last injection 24 h before being killed. 3. At the end of the experiment, rats in all three groups were fasted for 12 h and killed by cardiac puncture under ether anaesthesia. Blood samples were taken for the determination of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels and concentrations of tri-iodothyronine (T(3)) and thyroxine (T(4)). 4. It was found that MDA and SOD levels and concentrations of T(3) and T(4) were higher and the GSH level was lower in rats with hyperthyroidism compared with controls. Melatonin treatment decreased the elevated MDA and SOD levels and increased the lowered GSH level to control levels in rats with hyperthyroidism, but did not ameliorate the concentrations of T(3) and T(4). 5. It was concluded that high-dose melatonin treatment may decrease the hyperthyroidism-induced disturbances of lipid peroxidation and anti-oxidant enzyme activity and oxidative damage.

Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice.

PubMed

Arsov, Todor; Larter, Claire Z; Nolan, Christopher J; Petrovsky, Nikolai; Goodnow, Christopher C; Teoh, Narcissus C; Yeh, Matthew M; Farrell, Geoffrey C

2006-04-21

The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis, which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis; wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (fatty acid uptake; lipogenesis) and lipid disposal (fatty acid beta-oxidation; triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502e1 or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways.

Lipemia retinalis preceding acute pancreatitis.

PubMed

Horton, Matt; Thompson, Kelly

2011-08-01

Lipemia retinalis is a visible ophthalmic manifestation of severe hypertriglyceridemia. It may also be the only systemic sign present if triglycerides are acutely elevated in an asymptomatic patient. It may be the harbinger of more serious complications, such as acute pancreatitis and coronary artery disease. A 39-year-old woman presented for a diabetic eye examination. Dilated fundus examination found diffuse whitening of the retinal arteries and veins. The patient was asymptomatic without other remarkable ocular or systemic signs. The patient subsequently experienced an episode of acute pancreatitis. After a relative normalization of the triglyceride levels, the retina returned to baseline appearance. The patient's ocular health is monitored annually, and her endocrinologist modified the treatment regimen for improved lipid control. Although lipemia retinalis does not typically result in vision loss, it is a sign of a systemic condition that can have potentially fatal consequences. While the retinal appearance normalizes soon after resolution of the acute lipid imbalance, a multidisciplinary approach is necessary to obtain the desirable systemic outcome. Optometrists play a critical role in prompt referral of these patients for appropriate management of their lipids. Published by Elsevier Inc.

Phospholipid—polymer amphiphile hybrid assemblies and their interaction with macrophages

PubMed Central

Panneerselvam, Karthiga; Lynge, Martin E.; Riber, Camilla Frich; Mena-Hernando, Sofia; Smith, Anton A. A.; Goldie, Kenneth N.; Zelikin, Alexander N.; Städler, Brigitte

2015-01-01

Recently, the combination of lipids and block copolymers has become an alternative to liposomes and polymersomes as nano-sized drug carriers. We synthesize novel block copolymers consisting of poly(cholesteryl acrylate) as the hydrophobic core and poly(N-isopropylacrylamide) (PNIPAAm) as the hydrophilic extensions. Their successful phospholipid-assisted assembly into vesicles is demonstrated using the evaporation-hydration method. The preserved thermo-responsive property of the lipid-polymer hybrids is shown by a temperature dependent adsorption behaviour of the vesicles to poly(l lysine) coated surfaces. As expected, the vesicle adsorption is found to be higher at elevated temperatures. The cellular uptake efficiency of hybrids is assessed using macrophages with applied shear stress. The amount of adhering macrophages is affected by the time and level of applied shear stress. Further, it is found that shorter PNIPAAm extensions lead to higher uptake of the assemblies by the macrophages with applied shear stress. No inherent cytotoxicity is observed at the tested conditions. Taken together, this first example of responsive lipid-polymer hybrids, and their positive biological evaluation makes them promising nano-sized drug carrier candidates. PMID:26339330

Structural changes in the myocardium and serum lipid spectrum in experimental hypercholesterolemia and hypothyroidism.

PubMed

Nepomnyashchikh, L M; Lushnikova, E L; Polyakov, L P; Molodykh, O P; Klinnikova, M G; Russkikh, G S; Poteryaeva, O N; Nepomnyashchikh, R D; Pichigin, V I

2013-09-01

We studied the peculiarities of lipid spectrum of the blood and structural reorganization of the myocardium in experimental hypercholesterolemia with and without hypothyroidism. It was found that alimentary hypercholesterolemia accompanied by elevated total cholesterol, LDL, HDL, and triglyceride concentrations led to a decrease in body weight, heart weight, number of cardiomyocytes in the heart and induced pronounced lytic changes in cardiomyocytes, circulation disorders (sludge syndrome, echinocytosis of erythrocytes, lymphostasis), diffuse fibrosis of the stroma, and appearance of foam cells among diffuse mononuclear infiltrate cells. The combination of hypercholesterolemia with hypothyroid status caused more pronounced changes in the lipid spectrum and atherogenic index and more pronounced lytic and necrobiotic changes in cardiomyocytes. These findings suggest that elevated cholesterol concentrations in the blood, especially against the background of suppressed thyroid function, can directly induce considerable damage to cardiomyocytes, intramural vessels, and erythrocytes without the development of myocardial ischemia and in the absence of atherosclerotic plaques.

Effect of Weight Reduction on Cardiovascular Risk Factors and CD34-positive Cells in Circulation

PubMed Central

Mikirova, Nina A; Casciari, Joseph J; Hunninghake, Ronald E; Beezley, Margaret M

2011-01-01

Being overweight or obese is associated with an increased risk for the development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease. Dyslipidemia of obesity is characterized by elevated fasting triglycerides and decreased high-density lipoprotein-cholesterol concentrations. Endothelial damage and dysfunction is considered to be a major underlying mechanism for the elevated cardiovascular risk associated with increased adiposity. Alterations in endothelial cells and stem/endothelial progenitor cell function associated with overweight and obesity predispose to atherosclerosis and thrombosis. In our study, we analyzed the effect of a low calorie diet in combination with oral supplementation by vitamins, minerals, probiotics and human chorionic gonadotropin (hCG, 125-180 IUs) on the body composition, lipid profile and CD34-positive cells in circulation. During this dieting program, the following parameters were assessed weekly for all participants: fat free mass, body fat, BMI, extracellular/intracellular water, total body water and basal metabolic rate. For part of participants blood chemistry parameters and circulating CD34-positive cells were determined before and after dieting. The data indicated that the treatments not only reduced body fat mass and total mass but also improved the lipid profile. The changes in body composition correlated with the level of lipoproteins responsible for the increased cardiovascular risk factors. These changes in body composition and lipid profile parameters coincided with the improvement of circulatory progenitor cell numbers. As the result of our study, we concluded that the improvement of body composition affects the number of stem/progenitor cells in circulation. PMID:21850193

Effect of weight reduction on cardiovascular risk factors and CD34-positive cells in circulation.

PubMed

Mikirova, Nina A; Casciari, Joseph J; Hunninghake, Ronald E; Beezley, Margaret M

2011-01-01

Being overweight or obese is associated with an increased risk for the development of non-insulin-dependent diabetes mellitus, hypertension, and cardiovascular disease. Dyslipidemia of obesity is characterized by elevated fasting triglycerides and decreased high-density lipoprotein-cholesterol concentrations. Endothelial damage and dysfunction is considered to be a major underlying mechanism for the elevated cardiovascular risk associated with increased adiposity. Alterations in endothelial cells and stem/endothelial progenitor cell function associated with overweight and obesity predispose to atherosclerosis and thrombosis. In our study, we analyzed the effect of a low calorie diet in combination with oral supplementation by vitamins, minerals, probiotics and human chorionic gonadotropin (hCG, 125-180 IUs) on the body composition, lipid profile and CD34-positive cells in circulation. During this dieting program, the following parameters were assessed weekly for all participants: fat free mass, body fat, BMI, extracellular/intracellular water, total body water and basal metabolic rate. For part of participants blood chemistry parameters and circulating CD34-positive cells were determined before and after dieting. The data indicated that the treatments not only reduced body fat mass and total mass but also improved the lipid profile. The changes in body composition correlated with the level of lipoproteins responsible for the increased cardiovascular risk factors. These changes in body composition and lipid profile parameters coincided with the improvement of circulatory progenitor cell numbers. As the result of our study, we concluded that the improvement of body composition affects the number of stem/progenitor cells in circulation.

Life-history evolution and the microevolution of intermediary metabolism: activities of lipid-metabolizing enzymes in life-history morphs of a wing-dimorphic cricket.

PubMed

Zera, Anthony J; Zhao, Zhangwu

2003-03-01

Although a considerable amount of information is available on the ecology, genetics, and physiology of life-history traits, much more limited data are available on the biochemical and genetic correlates of life-history variation within species. Specific activities of five enzymes of lipid biosynthesis and two enzymes of amino acid catabolism were compared among lines selected for flight-capable (LW[f]) versus flightless (SW) morphs of the cricket Gryllus firmus. These morphs, which exist in natural populations, differ genetically in ovarian growth (100-400% higher in SW) and aspects of flight capability including the size of wings and flight muscles, and the concentration of triglyceride flight fuel (40% greater in LW[f]). Consistently higher activity of each enzyme in LW(f) versus SW-selected lines, and strong co-segregation between morph and enzyme activity, demonstrated genetically based co-variance between wing morph and enzyme activity. Developmental profiles of enzyme activities strongly paralleled profiles of triglyceride accumulation during adulthood and previous measures of in vivo lipid biosynthesis. These data strongly imply that genetically based elevation in activities of lipogenic enzymes, and enzymes controlling the conversion of amino acids into lipids, is an important cause underlying the elevated accumulation of triglyceride in the LW(f) morph, a key biochemical component of the trade-off between elevated early fecundity and flight capability. Global changes in lipid and amino-acid metabolism appear to have resulted from microevolutionary alteration of regulators of metabolism. Finally, strong genotype x environment (diet) interactions were observed for most enzyme activities. Future progress in understanding the functional causes of life-history evolution requires a more detailed synthesis of the fields of life-history evolution and metabolic biochemistry. Wing polymorphism is a powerful experimental model in such integrative studies.

Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

NASA Astrophysics Data System (ADS)

Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A.; Ghosh, Partha Pratim; Mitra, Prasenjit

2016-06-01

Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation.

Restoring Mitochondrial Function: A Small Molecule-mediated Approach to Enhance Glucose Stimulated Insulin Secretion in Cholesterol Accumulated Pancreatic beta cells

PubMed Central

Asalla, Suman; Girada, Shravan Babu; Kuna, Ramya S.; Chowdhury, Debabrata; Kandagatla, Bhaskar; Oruganti, Srinivas; Bhadra, Utpal; Bhadra, Manika Pal; Kalivendi, Shasi Vardhan; Rao, Swetha Pavani; Row, Anupama; Ibrahim, A; Ghosh, Partha Pratim; Mitra, Prasenjit

2016-01-01

Dyslipidemia, particularly the elevated serum cholesterol levels, aggravate the pathophysiology of type 2 diabetes. In the present study we explored the relationship between fasting blood sugar and serum lipid parameters in human volunteers which revealed a significant linear effect of serum cholesterol on fasting blood glucose. Short term feeding of cholesterol enriched diet to rodent model resulted in elevated serum cholesterol levels, cholesterol accumulation in pancreatic islets and hyperinsulinemia with modest increase in plasma glucose level. To explore the mechanism, we treated cultured BRIN-BD11 pancreatic beta cells with soluble cholesterol. Our data shows that cholesterol treatment of cultured pancreatic beta cells enhances total cellular cholesterol. While one hour cholesterol exposure enhances insulin exocytosis, overnight cholesterol accumulation in cultured pancreatic beta cells affects cellular respiration, and inhibits Glucose stimulated insulin secretion. We further report that (E)-4-Chloro-2-(1-(2-(2,4,6-trichlorophenyl) hydrazono) ethyl) phenol (small molecule M1) prevents the cholesterol mediated blunting of cellular respiration and potentiates Glucose stimulated insulin secretion which was abolished in pancreatic beta cells on cholesterol accumulation. PMID:27282931

Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications.

PubMed

Liu, Xinle; Gan, Wei; Zou, Yuangao; Yang, Bin; Su, Zhenzhen; Deng, Jin; Wang, Lanlan; Cai, Jianping

2016-01-01

The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age- and sex-matched healthy controls. Urinary levels of DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8-oxodGuo and 8-oxoGuo in diabetes patients with/without complications compared with age-matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8-oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8-oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications.

Hypolipidemic activity of Phellinus rimosus against triton WR-1339 and high cholesterol diet induced hyperlipidemic rats.

PubMed

Rony, K A; Ajith, T A; Nima, N; Janardhanan, K K

2014-03-01

Patients with the risk for atherosclerotic disease will be targeted to reduce the existing hyperlipidemia. The hypolipidemic activity of Phellinus rimosus was studied using triton WR-1339 and high cholesterol diet (HCD) induced models. The triton induced elevated lipid profile was attenuated by P. rimosus or standard drug atorvastatin. Similarly, administration of P. rimosus along with HCD significantly decline serum triglyceride, total cholesterol, low-density lipoprotein, with elevating the high-density lipoprotein. Thiobarbituric acid reacting substances in heart and liver significantly decreased; where as activity of enzymatic antioxidants and level of reduced glutathione were significantly increased. In both models, P. rimosus extract showed a significant ameliorative effect on the elevated atherogenic index as well as LDL/HDL-C ratio. The hypolipidemic activity of P. rimosus can be ascribed to its inhibitory effect on the liver HMG CoA reductase activity. The results suggest the possible therapeutic potential of this fungus as hypolipidemic agent. Copyright © 2014 Elsevier B.V. All rights reserved.

Elevated Stearoyl-CoA Desaturase in Brains of Patients with Alzheimer's Disease

PubMed Central

Astarita, Giuseppe; Jung, Kwang-Mook; Vasilevko, Vitaly; DiPatrizio, Nicholas V.; Martin, Sarah K.; Cribbs, David H.; Head, Elizabeth; Cotman, Carl W.; Piomelli, Daniele

2011-01-01

The molecular bases of Alzheimer's disease (AD) remain unclear. We used a lipidomic approach to identify lipid abnormalities in the brains of subjects with AD (N = 37) compared to age-matched controls (N = 17). The analyses revealed statistically detectable elevations in levels of non-esterified monounsaturated fatty acids (MUFAs) and mead acid (20:3n-9) in mid-frontal cortex, temporal cortex and hippocampus of AD patients. Further studies showed that brain mRNAs encoding for isoforms of the rate-limiting enzyme in MUFAs biosynthesis, stearoyl-CoA desaturase (SCD-1, SCD-5a and SCD-5b), were elevated in subjects with AD. The monounsaturated/saturated fatty acid ratio (‘desaturation index’) – displayed a strong negative correlation with measures of cognition: the Mini Mental State Examination test (r = −0.80; P = 0.0001) and the Boston Naming test (r = −0.57; P = 0.0071). Our results reveal a previously unrecognized role for the lipogenic enzyme SCD in AD. PMID:22046234

The correlation between serum free thyroxine and regression of dyslipidemia in adult males: A 4.5-year prospective study.

PubMed

Wang, Haoyu; Liu, Aihua; Zhou, Yingying; Xiao, Yue; Yan, Yumeng; Zhao, Tong; Gong, Xun; Pang, Tianxiao; Fan, Chenling; Zhao, Jiajun; Teng, Weiping; Shan, Zhongyan; Lai, Yaxin

2017-09-01

Elevated free thyroxine (FT4) levels may play a protective role in development of dyslipidemia. However, few prospective studies have been performed to definite the effects of thyroid hormones on the improvement of dyslipidemia and its components. Thus, this study aims to clarify the association between thyroid hormones within normal range and reversal of dyslipidemia in the absence of intervention.A prospective analysis including 134 adult males was performed between 2010 and 2014. Anthropometric parameters, thyroid function, and lipid profile were measured at baseline and during follow-up. Logistic regression and receiver operating characteristic (ROC) analysis were conducted to identify the variables in forecasting the reversal of dyslipidemia and its components.During 4.5-year follow-up, 36.6% (49/134) patients resolved their dyslipidemia status without drug intervention. Compared with the continuous dyslipidemia group, subjects in reversal group had elevated FT4 and high-density lipoprotein cholesterol (HDL-C) levels, as well as decreased total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels at baseline. Furthermore, baseline FT4 is negatively associated with the change percentages of TG (r = -0.286, P = .001), while positively associated with HDL-C (r = 0.227, P = .008). However, no correlation of lipid profile change percentages with FT3 and TSH were observed. Furthermore, the improving effects of baseline FT4 on dyslipidemia, high TG, and low HDL-C status were still observed after multivariable adjustment. In ROC analysis, areas under curve (AUCs) for FT4 in predicting the reversal of dyslipidemia, high TG, and low HDL-C were 0.666, 0.643, and 0.702, respectively (P = .001 for dyslipidemia, .018 for high TG, and .001 for low HDL-C).Higher FT4 value within normal range may ameliorate the dyslipidemia, especially high TG and low HDL-C status, in males without drug intervention. This suggests that a more flexible lipid-lowering therapy may be appropriate for patients with high-normal FT4.

CLOSED-LOOP STRIPPING ANALYSIS (CLSA) OF ...

EPA Pesticide Factsheets

Synthetic musk compounds are used as inexpensive fragrance materials for the production of perfumes and as additives to soap, detergent, and shampoo. They have been found in surface water, fish tissues, and human breast milk. The ubiquity of this class of compounds in the environment is attributable to high use and release into the environment. Current techniques for separating these compounds from fish tissues require tedious sample clean-up procedures. To obtain fat-free extracts, gel permeation chromatography (GPC), column chromatography using alumina, and silica gel, and thin layer chromatography (TLC clean-up procedures are frequently employed. Despite the considerable effort and resources devoted to these processes, a fraction of the lipids and lipid-like compounds frequently remains in the extracts. These low-level lipids foul injection liners, contaminate columns, and yield elevated baselines during gas chromatographic analysis of synthetic musk compounds. In this study, a simple method for the determination of synthetic musk compounds in fish tissues has been developed. Closed-loop stripping of saponified fish tissues in a I -L Wheaton purge- and-trap vessel, is used to strip compounds with high vapor pressures such as synthetic musks from the matrix onto a solid sorbent (Abselut Nexus). This technique is useful for screening biological tissues that contain lipids for musk compounds. Analytes are desorbed from the sorbent trap sequentially with polar an

Impact of Lipid Oxidization on Vertical Structures and Electrostatics of Phospholipid Monolayers Revealed by Combination of Specular X-ray Reflectivity and Grazing-Incidence X-ray Fluorescence.

PubMed

Korytowski, Agatha; Abuillan, Wasim; Makky, Ali; Konovalov, Oleg; Tanaka, Motomu

2015-07-30

The influence of phospholipid oxidization of floating monolayers on the structure perpendicular to the global plane and on the density profiles of ions near the lipid monolayer has been investigated by a combination of grazing incidence X-ray fluorescence (GIXF) and specular X-ray reflectivity (XRR). Systematic variation of the composition of the floating monolayers unravels changes in the thickness, roughness and electron density of the lipid monolayers as a function of molar fraction of oxidized phospholipids. Simultaneous GIXF measurements enable one to qualitatively determine the element-specific density profiles of monovalent (K(+) or Cs(+)) and divalent ions (Ca(2+)) in the vicinity of the interface in the presence and absence of two types of oxidized phospholipids (PazePC and PoxnoPC) with high spatial accuracy (±5 Å). We found the condensation of Ca(2+) near carboxylated PazePC was more pronounced compared to PoxnoPC with an aldehyde group. In contrast, the condensation of monovalent ions could hardly be detected even for pure oxidized phospholipid monolayers. Moreover, pure phospholipid monolayers exhibited almost no ion specific condensation near the interface. The quantitative studies with well-defined floating monolayers revealed how the elevation of lipid oxidization level alters the structures and functions of cell membranes.

Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage.

PubMed

Belenky, Peter; Ye, Jonathan D; Porter, Caroline B M; Cohen, Nadia R; Lobritz, Michael A; Ferrante, Thomas; Jain, Saloni; Korry, Benjamin J; Schwarz, Eric G; Walker, Graham C; Collins, James J

2015-11-03

Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (?-lactams, aminoglycosides, quinolones). These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Potential of MR spectroscopy for assessment of glioma grading.

PubMed

Bulik, Martin; Jancalek, Radim; Vanicek, Jiri; Skoch, Antonin; Mechl, Marek

2013-02-01

Magnetic resonance spectroscopy (MRS) is an imaging diagnostic method based that allows non-invasive measurement of metabolites in tissues. There are a number of metabolites that can be identified by standard brain proton MRS but only a few of them has a clinical significance in diagnosis of gliomas including N-acetylaspartate, choline, creatine, myo-inositol, lactate, and lipids. In this review, we describe potential of MRS for grading of gliomas. Low-grade gliomas are generally characterized by a relatively high concentration of N-acetylaspartate, low level of choline and absence of lactate and lipids. The increase in creatine concentration indicates low-grade gliomas with earlier progression and malignant transformation. Progression in grade of a glioma is reflected in the progressive decrease in the N-acetylaspartate and myo-inositol levels on the one hand and elevation in choline level up to grade III on the other. Malignant transformation of the glial tumors is also accompanied by the presence of lactate and lipids in MR spectra of grade III but mainly grade IV gliomas. It follows that MRS is a helpful method for detection of glioma regions with aggressive growth or upgrading due to favorable correlation of the choline and N-acetylaspartate levels with histopathological proliferation index Ki-67. Thus, magnetic resonance spectroscopy is also a suitable method for the targeting of brain biopsies. Gliomas of each grade have some specific MRS features that can be used for improvement of the diagnostic value of conventional magnetic resonance imaging in non-invasive assessment of glioma grade. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Amide-linked Ethanolamine Conjugate of Gemfibrozil as a Profound HDL Enhancer: Design, Synthesis, Pharmacological Screening and Docking Study.

PubMed

Rai, Himanshu; Dhaneshwar, Suneela S

2015-01-01

Elevated concentration of any or all types of lipids in the plasma including hypertriglyceridemia and hypercholesterolemia leads to atherosclerotic cardiovascular disease. Effective medication needs multiple drug therapy as recommended cholesterol and triglyceride levels are difficult to achieve by monotherapy and frequently require the use of more than one lipid-lowering medication. Gemfibrozil lowers plasma triglyceride-rich lipoproteins mainly VLDL and increases HDL. It is associated with short plasma half-life (1.5h) and GIT distress on long term use. In a study it was found that ethanolamine decreases serum cholesterol, especially VLDL cholesterol and LDL cholesterol in rats fed an HF/HC diet. In the present work, we thought of exploring the effect of co-drug of gemfibrozil with ethanolamine (GE-I) as a potential combination therapy for the management of mixed hyperlipidemia. Synthesis of GE-I was effected by CDI coupling. Structure was confirmed spectrally. Interestingly kinetic studies revealed that GE-I resisted chemical and enzymatic hydrolysis. In tritoninduced hyperlipidemia, significant lowering of serum lipid levels was observed. The hallmark of GEI was its profound effect on HDL level which was raised above the normal level by 15%. Docking study also supported modulatory effect of GE-I (docking score -7.012) on PPAR-α which was comparable to docking score of gemfibrozil (-9.432). These preliminary observations prompt us to consider GE-I as a novel, serendipitous, hybrid anti-hyperlipidemic new chemical entity which needs be studied extensively to prove it as an HDL enhancing anti-hyperlipidemic agent.

Complementary and alternative medicine for lowering blood lipid levels: A systematic review of systematic reviews.

PubMed

Posadzki, Paul; AlBedah, Abdullah M N; Khalil, Mohamed M K; AlQaed, Meshari S

2016-12-01

The aim of this article is to summarize and critically evaluate the evidence from systematic reviews (SRs) of complementary and alternative medicine (CAM) for lowering blood lipid levels (BLL). Eight electronic databases were searched until March 2016. Additionally, all the retrieved references were inspected manually for further relevant papers. Systematic reviews were considered eligible, if they included patients of any age and/or gender with elevated blood lipid levels using any type of CAM. We used the Oxman and AMSTAR criteria to critically appraise the methodological quality of the included SRs. Twenty-seven SRs were included in the analyses. The majority of the SRs were of high methodological quality (mean Oxman score=4.81, SD=4.88; and the mean AMSTAR score=7.22, SD=3.38). The majority of SRs (56%) arrived at equivocal conclusions (of these 8 were of high quality); 7 SRs (37%) arrived at positive conclusions (of these 6 were of high quality), and 2 (7%) arrived at negative conclusions (both were of high quality). There was conflicting evidence regarding the effectiveness of garlic; and promising evidence for yoga. To conclude, the evidence from SRs evaluating the effectiveness of CAM in lowering BLL is predominantly equivocal and confusing. Several limitations exist, such as variety of doses and preparations, confounding effects of diets and lifestyle factors, or heterogeneity of the primary trials among others. Copyright © 2016. Published by Elsevier Ltd.

[ANTHROPOMETRIC INDICATORS AND CARDIOMETABOLIC EVENTS AMONG SCHOOL-AGED CHILDREN FROM SONORA, MEXICO].

PubMed

Peralta Peña, Sandra Lidia; Reséndiz González, Eunice; Rubí Vargas, María; Terrazas Medina, Efraín Alonso; Cupul Uicab, Lea Aurora

2015-10-01

obesity in childhood is predictive of obesity in adulthood and it is associated with adverse health effect apparent since childhood; however, the joint assessment of obesity and adverse events among children in clinical settings is unusual. to assess the association of overweight and obesity, abdominal obesity, and excess body fat with systolic [SBP] and diastolic [DBP] blood pressure, lipid profile and glucose levels; and to identify the best anthropometric indicator of such events. we conducted a cross-sectional study in a sample of 412 schoolchildren. The presence of overweight and obesity, abdominal obesity and excess body fat was determined among all participants; levels of total cholesterol, triglycerides, high and low density lipoproteins, and glucose were measured in a subsample (n = 133). The associations of interest were assessed using adjusted linear and logistic regression models. 33% of the children were overweight or obese. Overall, overweight, obesity, abdominal obesity, and excess body fat were associated with elevated SBP and DBP and with a lipid profile and glucose levels that could indicate health risks among these children. Overweight and obesity were the best predictors of such events. among these school-aged children, we observed that obesity was associated with high odds of having adverse health outcomes such as high blood pressure, lipids and glucose. Such adverse events can be predicted by the presence of obesity measured by BMI, which is a noninvasive, inexpensive and easy to implement measure. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Late-onset dietary restriction compensates for age-related increase in oxidative stress and alterations of HSP 70 and synapsin 1 protein levels in male Wistar rats.

PubMed

Sharma, Sandeep; Singh, Rumani; Kaur, Manpreet; Kaur, Gurcharan

2010-04-01

Numerous reports implicate increased oxidative stress in the functional and structural changes occurring in the brain and other organs as a part of the normal aging process. Dietary restriction (DR) has long been shown to be life-prolonging intervention in several species. This study was aimed to assess the potential efficacy of late-onset short term DR when initiated in 21 months old male wistar rats for 3 months on the antioxidant defense system and lipid peroxidation, cellular stress response protein HSP 70 and synaptic marker protein synapsin 1 in discrete brain regions such as cortex, hypothalamus, and hippocampus as well as liver, kidney and heart from 24 month old rats. Age-associated decline in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and elevated levels of lipid peroxidation was observed in brain and peripheral organ as well as increased expression of HSP 70 and reduction in synapsin 1 was observed in brain studied. Late-onset short term DR was effective in partially restoring the antioxidant status and in decreasing lipid peroxidation level as well as enhancing the expression of HSP 70 and synapsin 1 in aged rats. Late onset short term DR also prevented age-related neurodegeneration as revealed by Fluoro-Jade B staining in hippocampus and cortex regions of rat brain. Thus our current results suggest that DR initiated even in old age has the potential to improve age related decline in body functions.

Estimation of serum malondialdehyde and assessment of DNA damage using comet assay in patients with oral submucous fibrosis.

PubMed

Paulose, Swetha; Rangdhol, Vishwanath; Ramesh, Ramasamy; Jeelani, Siccandar Ali; Brooklyin, Sivakumar

2016-08-01

To quantify the level of serum malondialdehyde and extent of DNA damage using comet assay in patients with oral submucous fibrosis (SMF) in comparison to normal individuals and to correlate the extent of DNA damage with MDA levels. Study included 30 cases of SMF (n = 30) and equal number of healthy volunteers. Serum malondialdehyde was measured using the thiobarbituric-trichloroacetitic acid (TBA-TCA) method. Comet assay was used to assess the DNA damage. Association between the extent of DNA damage and serum MDA levels was analyzed in SMF statistically. Comet assay results showed that there was an increase in tail length, percentage of tail DNA and tail moment among SMF subjects (P < 0.05). Serum MDA levels were elevated in SMF patients compared with healthy subjects. A significant positive correlation was observed between serum MDA levels and comet tail length in SMF group (r = 0.56; P < 0.05). Patients with SMF have increased DNA damage and elevated levels of lipid peroxidation compared with healthy controls. Evaluation of MDA levels as an oxidative biomarker along with comet assay analysis will serve as a diagnostic tool to identify patients with high risk of malignant potential in SMF. © 2015 Wiley Publishing Asia Pty Ltd.

Low circulating levels of IGF-1 in healthy adults are associated with reduced β-cell function, increased intramyocellular lipid, and enhanced fat utilization during fasting.

PubMed

Thankamony, Ajay; Capalbo, Donatella; Marcovecchio, M Loredana; Sleigh, Alison; Jørgensen, Sine Wanda; Hill, Nathan R; Mooslehner, Katrin; Yeo, Giles S H; Bluck, Les; Juul, Anders; Vaag, Allan; Dunger, David B

2014-06-01

Low serum IGF-1 levels have been linked to increased risk for development of type 2 diabetes. However, the physiological role of IGF-1 in glucose metabolism is not well characterized. Our objective was to explore glucose and lipid metabolism associated with variations in serum IGF-1 levels. IGF-1 levels were measured in healthy, nonobese male volunteers aged 18 to 50 years from a biobank (n = 275) to select 24 subjects (age 34.8 ± 8.9 years), 12 each in the lowest (low-IGF) and highest (high-IGF) quartiles of age-specific IGF-1 SD scores. Evaluations were undertaken after a 24-hour fast and included glucose and glycerol turnover rates using tracers, iv glucose tolerance test to estimate peripheral insulin sensitivity (IS) and acute insulin and C-peptide responses (indices of insulin secretion), magnetic resonance spectroscopy to measure intramyocellular lipids (IMCLs), calorimetry, and gene expression studies in a muscle biopsy. Acute insulin and C-peptide responses, IS, and glucose and glycerol rate of appearance (Ra) were evaluated. Fasting insulin and C-peptide levels and glucose Ra were reduced (all P < .05) in low-IGF compared with high-IGF subjects, indicating increased hepatic IS. Acute insulin and C-peptide responses were lower (both P < .05), but similar peripheral IS resulted in reduced insulin secretion adjusted for IS in low-IGF subjects (P = 0.044). Low-IGF subjects had higher overnight levels of free fatty acids (P = .028) and β-hydroxybutyrate (P = .014), increased accumulation of IMCLs in tibialis anterior muscle (P = .008), and a tendency for elevated fat oxidation rates (P = .058); however, glycerol Ra values were similar. Gene expression of the fatty acid metabolism pathway (P = .0014) was upregulated, whereas the GLUT1 gene was downregulated (P = .005) in the skeletal muscle in low-IGF subjects. These data suggest that serum IGF-1 levels could be an important marker of β-cell function and glucose as well as lipid metabolic responses during fasting.

Raising high-density lipoprotein cholesterol with reduction of cardiovascular risk: the role of nicotinic acid--a position paper developed by the European Consensus Panel on HDL-C.

PubMed

Chapman, M John; Assmann, Gerd; Fruchart, Jean-Charles; Shepherd, James; Sirtori, Cesare

2004-08-01

Reduction of low-density lipoprotein cholesterol (LDL-C) is presently the primary focus of lipid-lowering therapy for prevention and treatment of coronary heart disease (CHD). However, the high level of residual risk among statin-treated patients in recent coronary prevention studies indicates the need for modification of other major components of the atherogenic lipid profile. There is overwhelming evidence that a low plasma level of high-density lipoprotein cholesterol (HDL-C) is an important independent risk factor for CHD. Moreover, a substantial proportion of patients with or at risk of developing premature CHD typically exhibit distinct lipid abnormalities, including low HDL-C levels. Thus, therapeutic intervention aimed at raising HDL-C, within the context of reducing global cardiovascular risk, would benefit such patients, a viewpoint increasingly adopted by international treatment guidelines. Therapeutic options for patients with low HDL-C include treatment with statins, fibrates and nicotinic acid, either as monotherapy or in combination. Of these options, nicotinic acid is not only the most potent agent for raising HDL-C but is also effective in reducing key atherogenic lipid components including triglyceride-rich lipoproteins (mainly very low-density lipoproteins [VLDL] and VLDL remnants), LDL-C, and lipoprotein(a). The principal features of the atherogenic lipid profile in type 2 diabetes and the metabolic syndrome make them logical targets for nicotinic acid therapy, either alone or in combination with a statin. The lack of comprehensive European data on the prevalence of low HDL-C levels highlights a critical need for education on the importance of raising HDL-C in CHD prevention and treatment. The development of a reliable and accurate assay for HDL-C, as well as clarification of criteria for low and optimal levels of HDL-C in both men and women, constitute critical factors in the reliable identification and treatment of patients at elevated risk of CHD due to low HDL-C. Based on the available evidence, the European Consensus Panel recommends that the minimum target for HDL-C should be 40 mg/dL (1.03 mmol/L) in patients with CHD or with a high level of risk for CHD, including patients at high global risk with type 2 diabetes or the metabolic syndrome.

Preliminary comparative study on the effect of different chinese drugs for strengthening Pi in antagonizing diet induced obesity.

PubMed

Li, Xiao; Jiang, Ping; Fu, Chang-geng

2010-04-01

To observe the difference in fatty degree, glucose-lipid disorder and adipose-hormones between diet induced obesity (DIO) rats and diet induced obesity resistance (DIO-R) rats, and to explore the effect and acting mechanism of Chinese drugs for strengthening Pi (CD-SP) and those for both strengthening Pi and dissolving phlegm (CD-SPDP) in inhibiting obesity. Excepting eight rats allocated in the blank control group, the other 54 rats were fed with high-lipid forage for 12 weeks to establish models of obesity. Finally, 30 DIO rats and 8 DIO-R rats (shown by their body weight) were obtained. The DIO rats were divided into three groups, which were given gastric perfusion, respectively, with normal saline (Group A), CD-SP (Group B), and CD-SPDP (Group C). Fourteen weeks later, the animals' body weight (BW), length (BL), blood levels of fasting insulin (FIn), fasting glucose (FBG), triglyceride (TG), cholesterol (TC), leptin (LP), neuropeptide Y (NPY), C-reactive protein (CRP), tumor necrosis factor-alpha(TNF-alpha), adiponectin (AN), and resistin (RS) were measured; insulin resistance index (IRI) was calculated, and the degree of obesity and lipid content in abdominal cavity of rats were estimated. Moreover, the levels of LP, CRP, TNF-alpha, AN and RS in homogenate of rats' adipose tissues (ATH) were determined. After 12 weeks of high-lipid diet, the BW of DIO rats was higher than that of normal or DIO-R rats. After a 14-week continuous high-lipid diet feeding, in DIO rats, BW, lipid coefficient (LC), and IRI were significantly increased (P<0.01); serum levels of TNF-alpha, LP and AN were lower, NPY was higher, while the ATH levels of LP and AN were lower and TNF-alpha was higher in DIO rats than in DIO-R rats (P<0.05 or P<0.01); blood levels of FBG and lipids in DIO rats showed an increasing trend but was statistically insignificant (P>0.05); no significant difference was found in serum levels of CRP and RS due to the overly high data dispersion. Comparisons of the 3 DIO groups showed that BW, body weight index (BWI), LC and IRI were significantly lowered after treatment (P<0.01) in Group C, while these indexes were not significantly different between Group A and B; the serum levels of TNF-alpha, LP, and AN increased, NPY decreased in Group B and C, ATH levels of LP and AN increased, and TNF-alpha decreased in the two groups; but NPY, LP, and AN in blood and ATH were higher in Group C than those in Group B (P<0.05 or P<0.01). CD-SPDP could inhibit DIO and IR, showing that the effect is better than that of CD-SP, and its mechanism is related to promotion of LP and AN secretion and elevation of serum NPY.

Acute β-Hydroxy-β-Methyl Butyrate Suppresses Regulators of Mitochondrial Biogenesis and Lipid Oxidation While Increasing Lipid Content in Myotubes.

PubMed

Schnuck, Jamie K; Johnson, Michele A; Gould, Lacey M; Gannon, Nicholas P; Vaughan, Roger A

2016-10-01

Leucine modulates synthetic and degradative pathways in muscle, possibly providing metabolic benefits for both athletes and diseased populations. Leucine has become popular among athletes for improving performance and body composition, however little is known about the metabolic effects of the commonly consumed leucine-derived metabolite β-hydroxy-β-methyl butyrate (HMB). Our work measured the effects of HMB on metabolic protein expression, mitochondrial content and metabolism, as well as lipid content in skeletal muscle cells. Specifically, cultured C2C12 myotubes were treated with either a control or HMB ranging from 6.25 to 25 μM for 24 h and mRNA and/or protein expression, oxygen consumption, glucose uptake, and lipid content were measured. Contrary to leucine's stimulatory effect on metabolism, HMB-treated cells exhibited significantly reduced regulators of lipid oxidation including peroxisome proliferator-activated receptor alpha (PPARα) and PPARβ/δ, as well as downstream target carnitine palmitoyl transferase, without alterations in glucose or palmitate oxidation. Furthermore, HMB significantly inhibited activation of the master regulator of energetics, AMP-activated protein kinase. As a result, HMB-treated cells also displayed reduced total mitochondrial content compared with true control or cells equivocally treated with leucine. Additionally, HMB treatment amplified markers of lipid biosynthesis (PPARγ and fatty acid synthase) as well as consistently promoted elevated total lipid content versus control cells. Collectively, our results demonstrate that HMB did not improve mitochondrial metabolism or content, and may promote elevated cellular lipid content possibly through heightened PPARγ expression. These observations suggest that HMB may be most beneficial for populations interested in stimulating anabolic cellular processes.

Dopaminergic Neurons Respond to Iron-Induced Oxidative Stress by Modulating Lipid Acylation and Deacylation Cycles

PubMed Central

Sánchez Campos, Sofía; Rodríguez Diez, Guadalupe; Oresti, Gerardo Martín; Salvador, Gabriela Alejandra

2015-01-01

Metal-imbalance has been reported as a contributor factor for the degeneration of dopaminergic neurons in Parkinson Disease (PD). Specifically, iron (Fe)-overload and copper (Cu) mis-compartmentalization have been reported to be involved in the injury of dopaminergic neurons in this pathology. The aim of this work was to characterize the mechanisms of membrane repair by studying lipid acylation and deacylation reactions and their role in oxidative injury in N27 dopaminergic neurons exposed to Fe-overload and Cu-supplementation. N27 dopaminergic neurons incubated with Fe (1mM) for 24 hs displayed increased levels of reactive oxygen species (ROS), lipid peroxidation and elevated plasma membrane permeability. Cu-supplemented neurons (10, 50 μM) showed no evidence of oxidative stress markers. A different lipid acylation profile was observed in N27 neurons pre-labeled with [3H] arachidonic acid (AA) or [3H] oleic acid (OA). In Fe-exposed neurons, AA uptake was increased in triacylglycerols (TAG) whereas its incorporation into the phospholipid (PL) fraction was diminished. TAG content was 40% higher in Fe-exposed neurons than in controls. This increase was accompanied by the appearance of Nile red positive lipid bodies. Contrariwise, OA incorporation increased in the PL fractions and showed no changes in TAG. Lipid acylation profile in Cu-supplemented neurons showed AA accumulation into phosphatidylserine and no changes in TAG. The inhibition of deacylation/acylation reactions prompted an increase in oxidative stress markers and mitochondrial dysfunction in Fe-overloaded neurons. These findings provide evidence about the participation of lipid acylation mechanisms against Fe-induced oxidative injury and postulate that dopaminergic neurons cleverly preserve AA in TAG in response to oxidative stress. PMID:26076361

Phosphoethanolamine Decoration of Neisseria gonorrhoeae Lipid A Plays a Dual Immunostimulatory and Protective Role during Experimental Genital Tract Infection

PubMed Central

Packiam, Mathanraj; Yedery, Roshan D.; Begum, Afrin A.; Carlson, Russell W.; Ganguly, Jhuma; Sempowski, Gregory D.; Ventevogel, Melissa S.; Shafer, William M.

2014-01-01

The induction of an intense inflammatory response by Neisseria gonorrhoeae and the persistence of this pathogen in the presence of innate effectors is a fascinating aspect of gonorrhea. Phosphoethanolamine (PEA) decoration of lipid A increases gonococcal resistance to complement-mediated bacteriolysis and cationic antimicrobial peptides (CAMPs), and recently we reported that wild-type N. gonorrhoeae strain FA1090 has a survival advantage relative to a PEA transferase A (lptA) mutant in the human urethral-challenge and murine lower genital tract infection models. Here we tested the immunostimulatory role of this lipid A modification. Purified lipooligosaccharide (LOS) containing lipid A devoid of the PEA modification and an lptA mutant of strain FA19 induced significantly lower levels of NF-κB in human embryonic kidney Toll-like receptor 4 (TLR4) cells and murine embryonic fibroblasts than wild-type LOS of the parent strain. Moreover, vaginal proinflammatory cytokines and chemokines were not elevated in female mice infected with the isogenic lptA mutant, in contrast to mice infected with the wild-type and complemented lptA mutant bacteria. We also demonstrated that lptA mutant bacteria were more susceptible to human and murine cathelicidins due to increased binding by these peptides and that the differential induction of NF-κB by wild-type and unmodified lipid A was more pronounced in the presence of CAMPs. This work demonstrates that PEA decoration of lipid A plays both protective and immunostimulatory roles and that host-derived CAMPs may further reduce the capacity of PEA-deficient lipid A to interact with TLR4 during infection. PMID:24686069

Characterizing aquatic health using salmonid mortality, physiology, and biomass estimates in streams with elevated concentrations of arsenic, cadmium, copper, lead, and zinc in the Boulder River Watershed, Montana

USGS Publications Warehouse

Farag, Aïda M.; Skaar, Don; Nimick, David A.; MacConnell, Elizabeth; Hogstrand, Christer

2003-01-01

Abandoned tailings and mine adits are located throughout the Boulder River watershed in Montana. In this watershed, all species of fish are absent from some tributary reaches near mine sources; however, populations of brook trout Salvelinus fontitalis, rainbow trout Oncorhynchus mykiss, and cut-throat trout O. clarki are found further downstream. Multiple methods must be used to investigate the effects of metals released by past mining activity because the effects on aquatic life may range in severity, depending on the proximity of mine sources. Therefore, we used three types of effects—those on fish population levels (as measured by survival), those on biomass and density, and those at the level of the individual (as measured by increases in metallothionein, products of lipid peroxidation, and increases in concentrations of tissue metals)—to assess the aquatic health of the Boulder River watershed. Elevated concentrations of Cd, Cu, and Zn in the water column were associated with increased mortality of trout at sites located near mine waste sources. The hypertrophy (swelling), degeneration (dying), and necrosis of epithelial cells observed in the gills support our conclusion that the cause of death was related to metals in the water column. At a site further downstream (lower Cataract Creek), we observed impaired health of resident trout, as well as effects on biomass and density (measured as decreases in the kilograms of trout per hectare and the number per 300 m) and effects at the individual level, including increases in metallothionein, products of lipid peroxidation, and tissue concentrations of metals.

Ellagic and ferulic acids alleviate gamma radiation and aluminium chloride-induced oxidative damage.

PubMed

Salem, Ahmed M; Mohammaden, Tarek F; Ali, Mohamed A M; Mohamed, Enas A; Hasan, Hesham F

2016-09-01

Ionizing radiation interacts with biological systems through the generation of free radicals, which induce oxidative stress. Aluminium (Al) can negatively impact human health by direct interaction with antioxidant enzymes. Ellagic acid (EA) and Ferulic acid (FA) are plant polyphenolic compounds, have gained attention due to their multiple biological activities. To date, no studies investigating the antioxidant effect of EA/FA in a model involving both γ radiation and aluminium chloride (AlCl3) have been reported. Herein, we investigated the protective effect of EA and FA against oxidative stress induced by γ radiation and AlCl3 in rats. Rats were divided into thirteen groups: a negative control group, 3 positive control groups (γ-irradiated, AlCl3-treated and γ-irradiated+AlCl3-treated) and 9 groups (3 γ-irradiated, 3 AlCl3-treated and 3 γ-irradiated+AlCl3-treated) treated with EA and/or FA. Liver function and lipid profile were assessed. Levels of lipid peroxidation, protein oxidation and endogenous antioxidants as well as the concentrations of copper, iron and zinc were estimated in liver tissue homogenate. Furthermore, liver tissue sections were histologically examined. Oral administration of EA and/or FA resulted in 1) amelioration of AlCl3 and/or γ-radiation-induced hepatic function impairment, dyslipidemia and hepatic histological alterations; 2) reduction in liver MDA and PCC levels; 3) elevation of liver CAT, GPx and SOD activity as well as GSH level; 4) elevation in liver Cu concentrations which was accompanied by a reduction in Fe and Zn concentrations. Oral administration of EA and/or FA may be useful for ameliorating γ radiation and/or AlCl3-induced oxidative damage. Copyright © 2016 Elsevier Inc. All rights reserved.

The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reue, K.; Rehnmark, S.; Cohen, R.D.

1997-07-01

Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and thesemore » droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.« less

Protective effects of the herbal medicine goshajinkigan in a rat model of non-alcoholic fatty liver disease.

PubMed

Hirotani, Yoshihiko; Doi, Ayae; Takahashi, Tomoki; Umezawa, Hanako; Urashima, Yoko; Myotoku, Mitiaki

2012-12-01

This study was designed to investigate the effect of an herbal medicine-goshajinkigan (GJ)-on the regulation of total body weight, as well as liver and adipose tissue weights in rats fed a highfat diet (HFD) and drinking of 30% sucrose (HFDS) (HFD; the rats received 19.6% energy from carbohydrates, 18.2% from proteins, and 62.2% from lipids; total energy, 506 kcal/100 g). Control rats were fed a standard diet (the rats received 60.5% energy from carbohydrates, 26.2% from proteins, and 13.3% from lipids; total energy, 360 kcal/100 g). Over a period of 12 weeks, rats were allowed free access to either the standard diet or HFDS containing 0, 1, or 3% GJ. In comparison with the control group, the HFDS rats showed a significant decrease in overall body weight and adipose tissue weight, and an increase in liver weight at 12 weeks. GJ treatment significantly reversed the HFDS-induced decrease in body and adipose tissue weight and reduced the elevated liver weight dose-dependently. Similarly, GJ reduced the elevated serum aspartate aminotransferase levels observed in HFDS rats. These results suggest that GJ may have the potential to alleviate damage to the liver in subjects with long-term consumption of HFDS.

Evaluation of Correlation of Blood Glucose and Salivary Glucose Level in Known Diabetic Patients.

PubMed

Gupta, Anjali; Singh, Siddharth Kumar; Padmavathi, B N; Rajan, S Y; Mamatha, G P; Kumar, Sandeep; Roy, Sayak; Sareen, Mohit

2015-05-01

Diabetes mellitus is a chronic heterogenous disease in which there is dysregulation of carbohydrates, protein and lipid metabolism; leading to elevated blood glucose levels. The present study was conducted to evaluate the correlation between blood glucose and salivary glucose levels in known diabetic patients and control group and also to evaluate salivary glucose level as a diagnostic tool in diabetic patients. A total number of 250 patients were studied, out of which 212 formed the study group and 38 formed the control group. Among 250 patients, correlation was evaluated between blood glucose and salivary glucose values which on analysis revealed Pearson correlation of 0.073. The p-value was 0.247, which was statistically non significant. Salivary glucose values cannot be considered as a diagnostic tool for diabetic individuals.

Effect of DanQi Pill on PPARα, lipid disorders and arachidonic acid pathway in rat model of coronary heart disease.

PubMed

Chang, Hong; Wang, Qiyan; Shi, Tianjiao; Huo, Kuiyuan; Li, Chun; Zhang, Qian; Wang, Guoli; Wang, Yuanyuan; Tang, Binghua; Wang, Wei; Wang, Yong

2016-03-22

Danqi pill (DQP) is one of the most widely prescribed formulas and has been shown to have remarkable protective effect on coronary heart disease (CHD). However, its regulatory effects on lipid metabolism disorders haven't been comprehensively studied so far. We aimed to explore the effects of DQP on Peroxisome Proliferator activated receptors α (PPARα), lipid uptake-transportation-metabolism pathway and arachidonic acid (AA)-mediated inflammation pathway in rats with CHD. 80 Sprague-Dawley (SD) Rats were randomly divided into sham group, model group, positive control group and DQP group. Rat model of CHD was induced by ligation of left ventricle anterior descending artery and fed with high fat diet in all but the sham group. Rats in sham group only underwent thoracotomy. After surgery, rats in the positive control and DQP group received daily treatments of pravastatin and DQP respectively. At 28 days after surgery, rats were sacrificed and plasma lipids were evaluated by plasma biochemical detection. Western blot and PCR were applied to evaluate the expressions of PPARα, proteins involved in lipid metabolism and AA pathways. Twenty eight days after surgery, dyslipidemia developed in CHD model rats, as illustrated by elevated plasma lipid levels. Expressions of apolipoprotein A-I (ApoA-I), cluster of differentiation 36 (CD36) and fatty acid binding protein (FABP) in the heart tissues of model group were down-regulated compared with those in sham group. Expressions of carnitine palmitoyl transferase I (CPT-1A) and lipoproteinlipase (LPL) were also reduced significantly. In addition, levels of phospholipase A2 (PLA2) and cyclooxygenase 2 (COX-2) were up-regulated. Expressions of Nuclear factor-κB (NF- κB) and signal transducer and activator of transcription 3 (STAT3) also increased. Furthermore, Expression of PPARα decreased in the model group. DQP significantly up-regulated expressions of ApoA-I and FABP, as well as the expressions of CPT-1A and CD36. In addition, DQP down-regulated expressions of PLA2, COX-2 and NF-κB in inflammation pathway. Levels of STAT3 and LPL were not affected by DQP treatment. In particular, DQP up-regulated PPARα level significantly. DQP could effectively regulate lipid uptake-transportation-metabolism process in CHD model rats, and the effect is achieved mainly by activating ApoA-I-CD36-CPT-1A molecules. Interestingly, DQP can up-regulate expression of PPARα significantly. The anti-inflammatory effect of DQP is partly exerted by inhibiting expressions of PLA2-COX2 -NF-κB pathway.

High Triglycerides Are Associated with Low Thrombocyte Counts and High VEGF in Nephropathia Epidemica.

PubMed

Martynova, Ekaterina V; Valiullina, Aygul H; Gusev, Oleg A; Davidyuk, Yuriy N; Garanina, Ekaterina E; Shakirova, Venera G; Khaertynova, Ilsiyar; Anokhin, Vladimir A; Rizvanov, Albert A; Khaiboullina, Svetlana F

2016-01-01

Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome. Several reports have demonstrated a severe alteration in lipoprotein metabolism. However, little is known about changes in circulating lipids in NE. The objectives of this study were to evaluate changes in serum total cholesterol, high density cholesterol (HDCL), and triglycerides. In addition to evaluation of serum cytokine activation associations, changes in lipid profile and cytokine activation were determined for gender, thrombocyte counts, and VEGF. Elevated levels of triglycerides and decreased HDCL were observed in NE, while total cholesterol did not differ from controls. High triglycerides were associated with both the lowest thrombocyte counts and high serum VEGF, as well as a high severity score. Additionally, there were higher levels of triglycerides in male than female NE patients. Low triglycerides were associated with upregulation of IFN- γ and IL-12, suggesting activation of Th1 helper cells. Furthermore, levels of IFN- γ and IL-12 were increased in patients with lower severity scores, suggesting that a Th1 type immune response is playing protective role in NE. These combined data advance the understanding of NE pathogenesis and indicate a role for high triglycerides in disease severity.

High Triglycerides Are Associated with Low Thrombocyte Counts and High VEGF in Nephropathia Epidemica

PubMed Central

Valiullina, Aygul H.; Gusev, Oleg A.; Davidyuk, Yuriy N.; Garanina, Ekaterina E.; Shakirova, Venera G.; Khaertynova, Ilsiyar

2016-01-01

Nephropathia epidemica (NE) is a mild form of hemorrhagic fever with renal syndrome. Several reports have demonstrated a severe alteration in lipoprotein metabolism. However, little is known about changes in circulating lipids in NE. The objectives of this study were to evaluate changes in serum total cholesterol, high density cholesterol (HDCL), and triglycerides. In addition to evaluation of serum cytokine activation associations, changes in lipid profile and cytokine activation were determined for gender, thrombocyte counts, and VEGF. Elevated levels of triglycerides and decreased HDCL were observed in NE, while total cholesterol did not differ from controls. High triglycerides were associated with both the lowest thrombocyte counts and high serum VEGF, as well as a high severity score. Additionally, there were higher levels of triglycerides in male than female NE patients. Low triglycerides were associated with upregulation of IFN-γ and IL-12, suggesting activation of Th1 helper cells. Furthermore, levels of IFN-γ and IL-12 were increased in patients with lower severity scores, suggesting that a Th1 type immune response is playing protective role in NE. These combined data advance the understanding of NE pathogenesis and indicate a role for high triglycerides in disease severity. PMID:28053993

Hepatoprotective effect of Ginkgoselect Phytosome in rifampicin induced liver injury in rats: evidence of antioxidant activity.

PubMed

Naik, Suresh R; Panda, Vandana S

2008-09-01

The protective effects of Ginkgoselect Phytosome (GBP) on Rifampicin (RMP) induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. Liver damage was induced in Wistar rats by administering rifampicin (500 mg/kg, p.o.) daily for 30 days. Simultaneously, GBP at 25 mg/kg and 50 mg/kg, and the reference drug silymarin (100 mg/kg) were administered orally for 30 days/daily to RMP treated rats. Levels of marker enzymes (SGOT, SGPT and SALP), albaumin (Alb) and total proteins (TP) were assessed in serum. The effects of GBP on lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were assayed in liver homogenates to evaluate antioxidant activity. GBP (25 and 50 mg/kg) and silymarin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPX, GR, Alb and TP in a dose dependant manner. The present findings suggest that the hepatoprotective effect of GBP in RMP induced oxidative damage may be related to its antioxidant and free radical scavenging activity.

Spirulina platensis protects against gentamicin-induced nephrotoxicity in rats.

PubMed

Karadeniz, Ali; Yildirim, Abdulkadir; Simsek, Nejdet; Kalkan, Yildiray; Celebi, Fikret

2008-11-01

The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity.

Emergence of drug resistance-associated variants and changes in serum lipid profiles in sofosbuvir plus ledipasvir-treated chronic hepatitis C patients.

PubMed

Kan, Hiromi; Imamura, Michio; Kawakami, Yoshiiku; Daijo, Kana; Teraoka, Yuji; Honda, Fumi; Nakamura, Yuki; Morio, Kei; Kobayashi, Tomoki; Nakahara, Takashi; Nagaoki, Yuko; Kawaoka, Tomokazu; Tsuge, Masataka; Aikata, Hiroshi; Hayes, Clair Nelson; Miki, Daiki; Ochi, Hidenori; Honda, Yoji; Mori, Nami; Takaki, Shintaro; Tsuji, Keiji; Chayama, Kazuaki

2017-11-01

Combination of sofosbuvir plus ledipasvir therapy has been expected to enhance sustained virological response (SVR) rates in hepatitis C virus (HCV) genotype 1 chronic infected patients. We analyzed the emergence of drug resistance-associated variants (RAVs) in treatment failure and changes in lipid profiles in sofosbuvir/ledipasvir-treated patients. A total of 176 patients with chronic HCV genotype 1 infection without decompensated liver cirrhosis were treated with sofosbuvir/ledipasvir for 12 weeks. NS5A and NS5B RAVs were determined by either Invader assay or direct sequencing. Serum lipid-related markers were measured at the start of treatment and at week 4 in patients who received sofosbuvir/ledipasvir and ombitasvir/paritaprevir/ritonavir therapies. SVR was achieved in 94.9% (167 out of 176) of patients. SVR12 rate was 97.1% for patietns with low frequncy (<25%) of baseline NS5A RAVs, but 82.8% for patients with high frequency (>75%) of NS5A RAVs. In multivariate regression analysis, higher albumin (odds ratio [OR] = 0.020 for presence; P = 0.007), and NS5A-L31/Y93 RAVs with a population frequency <75% (OR = 29.860 for presence; P = 0.023) were identified as significant independent predictors for SVR12. NS5A-Y93H substitutions were detected in all nine treatment failures at HCV relapse, and three out of six patients with NS5A inhibitor-naïve patients achieved additional NS5A RAVs. Serum low-density lipoprotein cholesterol and apolipoprotein B levels were significantly elevated at week 4 in sofosbuvir/ledipasvir-treated patients. These elevations were greater than in ombitasvir/paritaprevir/ritonavir-treated patients. In conclusion, NS5A multi-RAVs are likely to develop in patients who fail to respond to sofosbuvir/ledipasvir therapy. Inhibition of HCV replication with sofosbuvir might affect lipid metabolism. © 2017 Wiley Periodicals, Inc.

Acyl CoA profiles of transgenic plants that accumulate medium-chain fatty acids indicate inefficient storage lipid synthesis in developing oilseeds.

PubMed

Larson, Tony R; Edgell, Teresa; Byrne, James; Dehesh, Katayoon; Graham, Ian A

2002-11-01

Several Brassica napus lines transformed with genes responsible for the synthesis of medium- or long-chain fatty acids were examined to determine limiting factor(s) for the subsequent accumulation of these fatty acids in seed lipids. Examination of a decanoic acid (10:0) accumulating line revealed a disproportionately high concentration of 10:0 CoA during seed development compared to long-chain acyl CoAs isolated from the same tissues, suggesting that poor incorporation of 10:0 CoA into seed lipids limits 10:0 fatty acid accumulation. This relationship was also seen for dodecanoyl (12:0) CoA and fatty acid in a high 12:0 line, but not for octadecanoic (18:0) CoA and fatty acid in a high 18:0 line. Comparison of 10:0 CoA and fatty acid proportions from seeds at different developmental stages for transgenic B. napus and Cuphea hookeriana, the source plant for the medium-chain thioesterase and 3-ketoacyl-ACP synthase transgenes, revealed that C. hookeriana incorporates 10:0 CoA into seed lipids more efficiently than transgenic B. napus. Furthermore, beta-oxidation and glyoxylate cycle activities were not increased above wild type levels during seed development in the 8:0/10:0 line, suggesting that lipid catabolism was not being induced in response to the elevated 10:0 CoA concentrations. Taken together, these data suggest that transgenic plants that are engineered to synthesize medium-chain fatty acids may lack the necessary mechanisms, such as specific acyltransferases, to incorporate these fatty acids efficiently into seed lipids.

Impaired adipogenesis in adipose tissue associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet.

PubMed

Yang, Shumin; Zhang, Wenlong; Zhen, Qianna; Gao, Rufei; Du, Tingting; Xiao, Xiaoqiu; Wang, Zhihong; Ge, Qian; Hu, Jinbo; Ye, Peng; Zhu, Qibo; Li, Qifu

2015-09-15

Chronic inflammation might be associated with hepatic lipid deposition independent of overnutrition. However, the mechanism is not fully understood. In this study, we investigate if impaired adipogenesis in adipose tissue is associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet. Casein injection in C57BL/6J mice was given every other day to induce chronic inflammation. All mice were sacrificed after 18weeks of injections. The serum, liver and adipose tissue were collected for analysis. Real-time polymerase chain reaction and western blotting were used to examine the gene and protein expressions of molecules involved in hepatic lipid metabolism and adipose adipogenesis. Casein injection elevated serum levels of insulin, free fatty acid (FFA) and proinflammatory factors. The gene expression of proinflammatory factors of adipose tissue and the liver also increased in the casein group as compared with the control group. Chronic inflammation up-regulated the hepatic expression of fatty acid translocase (CD36) and down-regulated microsomal triacylglycerol transfer protein (MTP), carnitine palmitoyltransferase 1a (CPT1a) and acyl-coenzyme a oxidase 1 (ACOX1). Meanwhile, chronic inflammation not only diminished the size of adipocytes, but also down-regulated the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding proteinα (C/EBPα), both indicating an impaired adipogenesis. Besides disturbed lipid metabolism in the liver per se, impaired adipogenesis in the adipose tissue might also be associated with hepatic lipid deposition induced by chronic inflammation in mice with chew diet. Copyright © 2015 Elsevier Inc. All rights reserved.

Lipidomic Components Alterations of Human Follicular Fluid Reveal the Relevance of Improving Clinical Outcomes in Women Using Progestin-Primed Ovarian Stimulation Compared to Short-Term Protocol.

PubMed

Wen, Xiaowei; Kuang, Yanping; Zhou, Lixia; Yu, Baofeng; Chen, Qiuju; Fu, Yonglun; Yan, Zheng; Guo, Haiyan; Lyu, Qifeng; Xie, Jun; Chai, Weiran

2018-05-21

BACKGROUND Increasing the success rate of in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) is a duty of clinicians that has made many seek a variety of protocols. This study was undertaken to use a liquid chromatography-mass spectrometry (LC-MS) to define the alterations of follicular fluid (FF) lipid metabolites in patients undergoing progestin-primed ovarian stimulation (PPOS) compared with short-term protocol, revealing potential correlations between the differentially expressed lipids and ameliorative clinical outcomes. MATERIAL AND METHODS Ninety-three infertile women undergoing IVF/ICSI treatment with PPOS (n=62) or a short-term protocol (n=31) were prospectively enrolled in a randomized controlled trial. FF samples were obtained from dominant follicles at the time of oocyte retrieval. Lipid metabolism profiles were analyzed using LC-MS. RESULTS Twelve lipids were found to be higher in patients treated with the PPOS protocol than in those receiving the short-term protocol, including triacylglycerols (TAG-34: 1+NH4, TAG-58: 0+NH4, TAG-64: 3+NH4, and TAG-64: 8+NH4), diacylglycerol DAG-38: 6+NH4, phosphatidylglycerols (PG-26: 0, PG-30: 2, and PG-40: 5), phosphatidylethanolamine PE-32: 2, lysophosphatidylethanolamine LPE-14: 1, lysophosphatidylinositol LPI-12: 0, and lysophosphatidylcholine LPC-16: 0. CONCLUSIONS Our data demonstrate that the PPOS protocol increases the levels of 12 lipids in FF, which reveals a strong association between the differentially elevated lipids and better IVF/ICSI outcomes.

Ramadan fasting ameliorates arterial pulse pressure and lipid profile, and alleviates oxidative stress in hypertensive patients.

PubMed

Al-Shafei, Ahmad I M

2014-06-01

Effects of Ramadan fasting on health are important. Its effects on arterial pulse pressure (PP), lipid profile and oxidative stress were characterized in hypertensives. PP, indices of lipid profile and oxidative stress were measured pre-, during and post-fasting in equal (40 each), sex- and age-matched groups (age 55 ± 5 years) of hypertensives (HT) and controls (C). Fasting reduced PP significantly by 17.2% and insignificantly by 9.3% in the HT and C groups, respectively. Total cholesterol (TC) was lowered insignificantly by 11.7% and 4.7% in the HT and C patients, respectively. Triglycerides (TG) and malondialdehyde (MDA) were significantly lowered by: TG: 24.5% and 22.8%; MDA: 45.6% and 54.3%; while glutathione (GSH) elevated by 56.8% and 52.6% in the HT and C groups, respectively. High-density lipoproteins (HDL) were raised significantly by 33.3% and insignificantly by 6.7%, whereas low-density lipoproteins (LDL) decreased significantly by 17.7% and insignificantly by 4.0% in the HT and C groups, respectively. At 6 weeks post-fasting, MDA remained significantly lower than the pre-fasting level by 24.3% and 25.7%, and GSH higher by 30.2% and 26.3% in the HT and C groups, respectively, while PP and TC returned to pre-fasting values in both groups. The post-fasting, HDL was significantly higher by 20.3% and LDL lower by 12.0% than the fasting levels in the HT patients. Fasting improves PP and lipids profile and ameliorates oxidative stress in hypertensives.

Enhanced glycogen metabolism in adipose tissue decreases triglyceride mobilization

PubMed Central

Markan, Kathleen R.; Jurczak, Michael J.; Allison, Margaret B.; Ye, Honggang; Sutanto, Maria M.; Cohen, Ronald N.

2010-01-01

Adipose tissue is a primary site for lipid storage containing trace amounts of glycogen. However, refeeding after a prolonged partial fast produces a marked transient spike in adipose glycogen, which dissipates in coordination with the initiation of lipid resynthesis. To further study the potential interplay between glycogen and lipid metabolism in adipose tissue, the aP2-PTG transgenic mouse line was utilized since it contains a 100- to 400-fold elevation of adipocyte glycogen levels that are mobilized upon fasting. To determine the fate of the released glucose 1-phosphate, a series of metabolic measurements were made. Basal and isoproterenol-stimulated lactate production in vitro was significantly increased in adipose tissue from transgenic animals. In parallel, basal and isoproterenol-induced release of nonesterified fatty acids (NEFAs) was significantly reduced in transgenic adipose tissue vs. control. Interestingly, glycerol release was unchanged between the genotypes, suggesting that enhanced triglyceride resynthesis was occurring in the transgenic tissue. Qualitatively similar results for NEFA and glycerol levels between wild-type and transgenic animals were obtained in vivo during fasting. Additionally, the physiological upregulation of the phosphoenolpyruvate carboxykinase cytosolic isoform (PEPCK-C) expression in adipose upon fasting was significantly blunted in transgenic mice. No changes in whole body metabolism were detected through indirect calorimetry. Yet weight loss following a weight gain/loss protocol was significantly impeded in the transgenic animals, indicating a further impairment in triglyceride mobilization. Cumulatively, these results support the notion that the adipocyte possesses a set point for glycogen, which is altered in response to nutritional cues, enabling the coordination of adipose glycogen turnover with lipid metabolism. PMID:20424138

Medium-chain triglycerides and monounsaturated fatty acids potentiate the beneficial effects of fish oil on selected cardiovascular risk factors in rats.

PubMed

Kondreddy, Vijay Kumar Reddy; Anikisetty, Maheswaraiah; Naidu, Kamatham Akhilender

2016-02-01

Fish oil (FO) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is known to reduce the risk of cardiovascular diseases (CVDs). Little information is known regarding the influence of lipid composition in the background diet on the modulatory effect of FO supplementation on CVDs. The present study was designed to investigate the influence of various background dietary lipids and FO on selected cardiovascular risk factors in rats. Adult Wistar rats were fed semisynthetic diet with FO at 1.0% or 2.0% along with other lipids, namely, medium-chain triacylglycerols (MCTs), monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs) and n-3 PUFAs, for 5 weeks. Some of the potent CVD risk factors were estimated in the rats. FO at 1.0% and 2.0% has significantly reduced serum lipid peroxides, total cholesterol, triglycerides (TAGs), tumor necrosis factor-α, interleukin-6 and C-reactive protein; liver and adipose TAG and cholesterol levels in MCT, MUFA and n-6 PUFA diet groups. Notably, these alterations were comparatively higher in 1.0% FO-substituted MCT and MUFA diet groups. Interestingly, feeding of FO along with n-3 PUFAs did not show additive effect in attenuation of these factors. Serum liver EPA and DHA levels were remarkably elevated in rats fed FO-enriched MCT or MUFA diets. Our results suggest that MCTs or MUFAs in the background diet might promote the beneficial effects of FO on CVDs. Copyright © 2015 Elsevier Inc. All rights reserved.

Quantitative proteomics analysis reveals perturbation of lipid metabolic pathways in the liver of Atlantic cod (Gadus morhua) treated with PCB 153.

PubMed

Yadetie, Fekadu; Oveland, Eystein; Døskeland, Anne; Berven, Frode; Goksøyr, Anders; Karlsen, Odd André

2017-04-01

PCB 153 is one of the most abundant PCB congeners detected in biological samples. It is a persistent compound that is still present in the environment despite the ban on production and use of PCBs in the late 1970s. It has strong tendencies to bioaccumulate and biomagnify in biota, and studies have suggested that it is an endocrine and metabolic disruptor. In order to study mechanisms of toxicity, we exposed Atlantic cod (Gadus morhua) to various doses of PCB 153 (0, 0.5, 2 and 8mg/kg body weight) for two weeks and examined the effects on expression of liver proteins using label-free quantitative proteomics. Label-free liquid chromatography-mass spectrometry analysis of the liver proteome resulted in the quantification of 1272 proteins, of which 78 proteins were differentially regulated in the PCB 153-treated dose groups compared to the control group. Functional enrichment analysis showed that pathways significantly affected are related to lipid metabolism, cytoskeletal remodeling, cell cycle and cell adhesion. Importantly, the main effects appear to be on lipid metabolism, with up-regulation of enzymes in the de novo fatty acid synthesis pathway, consistent with previous transcriptomics results. Increased plasma triglyceride levels were also observed in the PCB 153 treated fish, in agreement with the induction of the lipogenic genes and proteins. The results suggest that PCB 153 perturbs lipid metabolism in the Atlantic cod liver. Elevated levels of lipogenic enzymes and plasma triglycerides further suggest increased synthesis of fatty acids and triglycerides. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of flaxseed oil on anti-oxidative system and membrane deformation of human peripheral blood erythrocytes in high glucose level.

PubMed

Yang, Wei; Fu, Juan; Yu, Miao; Huang, Qingde; Wang, Di; Xu, Jiqu; Deng, Qianchun; Yao, Ping; Huang, Fenghong; Liu, Liegang

2012-07-08

The erythrocyte membrane lesion is a serious diabetic complication. A number of studies suggested that n-3 fatty acid could reduce lipid peroxidation and elevate α- or γ-tocopherol contents in membrane of erythrocytes. However, evidence regarding the protective effects of flaxseed oil, a natural product rich in n-3 fatty acid, on lipid peroxidation, antioxidative capacity and membrane deformation of erythrocytes exposed to high glucose is limited. Human peripheral blood erythrocytes were isolated and treated with 50 mM glucose to mimic hyperglycemia in the absence or presence of three different doses of flaxseed oil (50, 100 or 200 μM) in the culture medium for 24 h. The malondialdehyde (MDA) and L-glutathione (GSH) were measured by HPLC and LC/MS respectively. The phospholipids symmetry and membrane fatty acid composition of human erythrocytes were detected by flow cytometry and gas chromatograph (GC). The morphology of human erythrocyte was illuminated by ultra scanning electron microscopy. Flaxseed oil attenuated hyperglycemia-induced increase of MDA and decrease of GSH in human erythrocytes. Human erythrocytes treated with flaxseed oil contained higher C22:5 and C22:6 than those in the 50 mM glucose control group, indicating that flaxseed oil could reduce lipid asymmetric distribution and membrane perturbation. The ultra scanning electron microscopy and flow cytometer have also indicated that flaxseed oil could protect the membrane of human erythrocytes from deformation at high glucose level. The flaxseed oil supplementation may prevent lipid peroxidation and membrane dysfunction of human erythrocytes in hyperglycemia.

Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation.

PubMed

Jameel, Faizan; Phang, Melinda; Wood, Lisa G; Garg, Manohar L

2014-12-16

Recent studies have demonstrated a relationship between fructose consumption and risk of developing metabolic syndrome. Mechanisms by which dietary fructose mediates metabolic changes are poorly understood. This study compared the effects of fructose, glucose and sucrose consumption on post-postprandial lipemia and low grade inflammation measured as hs-CRP. This was a randomized, single blinded, cross-over trial involving healthy subjects (n=14). After an overnight fast, participants were given one of 3 different isocaloric drinks, containing 50 g of either fructose or glucose or sucrose dissolved in water. Blood samples were collected at baseline, 30, 60 and 120 minutes post intervention for the analysis of blood lipids, glucose, insulin and high sensitivity C-reactive protein (hs-CRP). Glucose and sucrose supplementation initially resulted in a significant increase in glucose and insulin levels compared to fructose supplementation and returned to near baseline values within 2 hours. Change in plasma cholesterol, LDL and HDL-cholesterol (measured as area under curve, AUC) was significantly higher when participants consumed fructose compared with glucose or sucrose (P<0.05). AUC for plasma triglyceride levels however remained unchanged regardless of the dietary intervention. Change in AUC for hs-CRP was also significantly higher in subjects consuming fructose compared with those consuming glucose (P<0.05), but not sucrose (P=0.07). This study demonstrates that fructose as a sole source of energy modulates plasma lipids and hsCRP levels in healthy individuals. The significance of increase in HDL-cholesterol with a concurrent increase in LDL-cholesterol and elevated hs-CRP levels remains to be delineated when considering health effects of feeding fructose-rich diets. ACTRN12614000431628.

Effect of lipid peroxidation, antioxidants, macro minerals and trace elements on eczema.

PubMed

Amin, Mohammad Nurul; Liza, Kaniz Fatema; Sarwar, Md Shahid; Ahmed, Jamiuddin; Adnan, Md Tareek; Chowdhury, Manjurul Islam; Hossain, Mohammad Zahid; Islam, Mohammad Safiqul

2015-09-01

The exact etiology and pathogenesis of eczema are not yet fully understood, although different factors are considered as pathogenic mechanisms in the development of eczema. Our study was designed to determine extent of serum lipid peroxidation, antioxidants, macro minerals and trace elements in patients with eczema, and thereby, find any pathophysiological correlation. The study was conducted as a case-control study with 65 eczema patients as cases and 65 normal healthy individuals as controls. Lipid peroxidation was assessed by measuring the serum level of malondialdehyde (MDA). Antioxidants- vitamin A and E concentration was determined by RP-HPLC method whereas vitamin C was evaluated for serum ascorbic acid by UV spectrophotometric method. Serum macro minerals (Na, K, Ca) and trace elements (Zn, Fe) were determined by Atomic Absorption Spectroscopy (AAS). This study found significantly higher level of MDA (p < 0.001) and lower level of antioxidants (p < 0.05) in patients in comparison to the control subjects. Analysis of serum macro minerals (Na, K and Ca) and trace elements (Zn, Fe) found that the mean values of Na, K, Ca, Zn and Fe were 2771.60 ± 75.64, 66.33 ± 3.03, 48.41 ± 2.50, 0.30 ± 0.02 and 0.29 ± 0.009 mg/L for the patient group and 3284.81 ± 34.51, 162.18 ± 3.72, 87.66 ± 2.10, 0.75 ± 0.06 and 0.87 ± 0.06 mg/L for the control group, accordingly. There was a significant difference for all the minerals between the patients and controls (p < 0.001). This study suggests a strong association between the pathogenesis of eczema with the elevated level of MDA and depleted level of antioxidants, macro minerals, and trace elements.

Fermentation of soy milk via Lactobacillus plantarum improves dysregulated lipid metabolism in rats on a high cholesterol diet.

PubMed

Kim, Yunhye; Yoon, Sun; Lee, Sun Bok; Han, Hye Won; Oh, Hayoun; Lee, Wu Joo; Lee, Seung-Min

2014-01-01

We aimed to investigate whether in vitro fermentation of soy with L. plantarum could promote its beneficial effects on lipids at the molecular and physiological levels. Rats were fed an AIN76A diet containing 50% sucrose (w/w) (CTRL), a modified AIN76A diet supplemented with 1% (w/w) cholesterol (CHOL), or a CHOL diet where 20% casein was replaced with soy milk (SOY) or fermented soy milk (FSOY). Dietary isoflavone profiles, serum lipids, hepatic and fecal cholesterol, and tissue gene expression were examined. The FSOY diet had more aglycones than did the SOY diet. Both the SOY and FSOY groups had lower hepatic cholesterol and serum triglyceride (TG) than did the CHOL group. Only FSOY reduced hepatic TG and serum free fatty acids and increased serum HDL-CHOL and fecal cholesterol. Compared to CHOL, FSOY lowered levels of the nuclear forms of SREBP-1c and SREBP-2 and expression of their target genes, including FAS, SCD1, LDLR, and HMGCR. On the other hand, FSOY elevated adipose expression levels of genes involved in TG-rich lipoprotein uptake (ApoE, VLDLR, and Lrp1), fatty acid oxidation (PPARα, CPT1α, LCAD, CYP4A1, UCP2, and UCP3), HDL-biogenesis (ABCA1, ApoA1, and LXRα), and adiponectin signaling (AdipoQ, AdipoR1, and AdipoR2), as well as levels of phosphorylated AMPK and ACC. SOY conferred a similar expression profile in both liver and adipose tissues but failed to reach statistical significance in many of the genes tested, unlike FSOY. Our data indicate that fermentation may be a way to enhance the beneficial effects of soy on lipid metabolism, in part via promoting a reduction of SREBP-dependent cholesterol and TG synthesis in the liver, and enhancing adiponectin signaling and PPARα-induced expression of genes involved in TG-rich lipoprotein clearance, fatty acid oxidation, and reverse cholesterol transport in adipose tissues.

Fermentation of Soy Milk via Lactobacillus plantarum Improves Dysregulated Lipid Metabolism in Rats on a High Cholesterol Diet

PubMed Central

Han, Hye Won; Oh, Hayoun; Lee, Wu Joo; Lee, Seung-Min

2014-01-01

We aimed to investigate whether in vitro fermentation of soy with L. plantarum could promote its beneficial effects on lipids at the molecular and physiological levels. Rats were fed an AIN76A diet containing 50% sucrose (w/w) (CTRL), a modified AIN76A diet supplemented with 1% (w/w) cholesterol (CHOL), or a CHOL diet where 20% casein was replaced with soy milk (SOY) or fermented soy milk (FSOY). Dietary isoflavone profiles, serum lipids, hepatic and fecal cholesterol, and tissue gene expression were examined. The FSOY diet had more aglycones than did the SOY diet. Both the SOY and FSOY groups had lower hepatic cholesterol and serum triglyceride (TG) than did the CHOL group. Only FSOY reduced hepatic TG and serum free fatty acids and increased serum HDL-CHOL and fecal cholesterol. Compared to CHOL, FSOY lowered levels of the nuclear forms of SREBP-1c and SREBP-2 and expression of their target genes, including FAS, SCD1, LDLR, and HMGCR. On the other hand, FSOY elevated adipose expression levels of genes involved in TG-rich lipoprotein uptake (ApoE, VLDLR, and Lrp1), fatty acid oxidation (PPARα, CPT1α, LCAD, CYP4A1, UCP2, and UCP3), HDL-biogenesis (ABCA1, ApoA1, and LXRα), and adiponectin signaling (AdipoQ, AdipoR1, and AdipoR2), as well as levels of phosphorylated AMPK and ACC. SOY conferred a similar expression profile in both liver and adipose tissues but failed to reach statistical significance in many of the genes tested, unlike FSOY. Our data indicate that fermentation may be a way to enhance the beneficial effects of soy on lipid metabolism, in part via promoting a reduction of SREBP-dependent cholesterol and TG synthesis in the liver, and enhancing adiponectin signaling and PPARα-induced expression of genes involved in TG-rich lipoprotein clearance, fatty acid oxidation, and reverse cholesterol transport in adipose tissues. PMID:24520358

N-3 polyunsaturated fatty acids supplementation does not affect changes of lipid metabolism induced in rats by altered thyroid status.

PubMed

Rauchová, H; Vokurková, M; Pavelka, S; Behuliak, M; Tribulová, N; Soukup, T

2013-07-01

Epidemiological studies have demonstrated that n-3 polyunsaturated fatty acid (PUFA) consumption is associated with a reduced risk of atherosclerosis and hyperlipidemia. It is well known that lipid metabolism is also influenced by thyroid hormones. The aim of our study was to test whether n-3 PUFA supplementation (200 mg/kg of body weight/day for 6 weeks given intragastrically) would affect lipid metabolism in Lewis male rats with altered thyroid status. Euthyroid, hypothyroid, and hyperthyroid status of experimental groups was well defined by plasma levels of triiodothyronine, the activity of liver mitochondrial glycerol-3-phosphate dehydrogenase, and by relative heart weight. Fasting blood glucose levels were significantly higher in the hyperthyroid compared to the euthyroid and hypothyroid rats (5.0±0.2 vs. 3.7±0.4 and 4.4±0.2 mmol/l, respectively). In hyperthyroid animals, the concentration of plasma postprandial triglycerides was also increased compared to euthyroid and hypothyroid rats (0.9±0.1 vs. 0.5±0.1 and 0.4±0.1 mmol/l, respectively). On the other hand, hypothyroidism compared to euthyroid and hyperthyroid status was associated with elevated plasma levels of total cholesterol (2.6±0.2 vs. 1.5±0.1 and 1.6±0.1 mmol/l, respectively), LDL cholesterol (0.9±0.1 vs. 0.4±0.1 and 0.2±0.1 mmol/l, respectively) as well as HDL cholesterol (1.6±0.1 vs. 1.0±0.1 and 1.3±0.1 mmol/l, respectively). Supplementation of n-3 PUFA in the present study did not significantly modify either relative heart weight or glucose and lipid levels in any thyroid status. © Georg Thieme Verlag KG Stuttgart · New York.

Serum lipidomics analysis of ovariectomized rats under Curcuma comosa treatment.

PubMed

Vinayavekhin, Nawaporn; Sueajai, Jetjamnong; Chaihad, Nichaboon; Panrak, Ratchanee; Chokchaisiri, Ratchanaporn; Sangvanich, Polkit; Suksamrarn, Apichart; Piyachaturawat, Pawinee

2016-11-04

Curcuma comosa Roxb. (C. comosa) or Wan Chak Motluk, Zingiberaceae family, has been used in Thai traditional medicine for the treatment of gynecological problems and inflammation. This study aimed to investigate the therapeutic potential of C. comosa by determining the changes in the lipid profiles in the ovariectomized rats, as a model of estrogen-deficiency-induced hyperlipidemia, after treatment with different components of C. comosa using an untargeted lipidomics approach. Lipids were extracted from the serum of adult female rats subjected to a sham operation (SHAM; control), ovariectomy (OVX), or OVX with 12-week daily doses of estrogen (17β-estradiol; E 2 ), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD; a phytoestrogen from C. comosa), powdered C. comosa rhizomes or its crude ethanol extract. They were then analyzed by liquid chromatography-mass spectrometry, characterized, and subjected to the orthogonal projections to latent structures discriminant analysis statistical model to identify tentative biomarkers. Levels of five classes of lipids (ceramide, ceramide-1-phosphate, sphingomyelin, 1-O-alkenyl-lysophosphatidylethanolamine and lysophosphatidylethanolamine) were elevated in the OVX rats compared to those in the SHAM rats, while the monoacylglycerols and triacylglycerols were decreased. The E 2 treatment only reversed the levels of ceramides, whereas treatments with DPHD, C. comosa extract or powder returned the levels of all upregulated lipids back to those in the SHAM control rats. The findings suggest the potential beneficial effects of C. comosa on preventing the increased ceramide levels in OVX rats, a possible cause of metabolic disturbance under estrogen deficiency. Overall, the results demonstrated the power of untargeted lipidomics in discovering disease-relevant biomarkers, as well as evaluating the effectiveness of treatment by C. comosa components (DPHD, extract or powder) as utilized in Thai traditional medicine, and also providing scientific support for its folklore use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Update on the National Cholesterol Education Program Adult Treatment Panel III guidelines: getting to goal.

PubMed

McKenney, James M

2003-09-01

Considerable data on the pathophysiology, epidemiology, and treatment of dyslipidemia-induced coronary heart disease (CHD) have accumulated in recent years. These data have been assessed and incorporated into the guidelines of the National Cholesterol Education Program Expert Panel on the Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel [ATP] III). A major focus of the new guidelines is the assessment of the near-term (i.e., 10-yr) risk of experiencing a CHD event and matching the intensity of treatment to this risk. Patients with diabetes and those with a greater than 20% 10-year risk of experiencing a CHD event have been elevated to the risk level of CHD equivalent. The ATP III guidelines also modify several lipid and lipoprotein classifications. A low-density lipoprotein cholesterol (LDL) level below 100 mg/dl is now considered optimum for all individuals. In addition, high-density lipoprotein cholesterol (HDL) and triglyceride cutoff points have been modified to reflect more accurately the risk associated with abnormalities in these lipoproteins. As with the previous guidelines, the primary target of therapy remains LDL. Therapeutic lifestyle changes consisting of diet, weight reduction, and increased physical activity should be included in all treatment regimens. Based on their potent LDL-lowering properties and their proven ability to decrease mortality in a variety of patient populations, statins are generally the first choice for pharmacologic therapy. A secondary target of therapy includes non-HDL goals for patients with high triglyceride levels and the metabolic syndrome, which is characterized by abdominal obesity, elevated triglyceride levels, low HDL levels, and insulin resistance. Management of these secondary targets includes weight reduction and increased physical activity, and treatment of the lipid and nonlipid risk factors. Overall, ATP III represents an aggressive approach to treating dyslipidemia, greatly extending the number of individuals who qualify for treatment.

Polybrominated diphenyl ethers (PBDEs) and organochlorines in small cetaceans from Hong Kong waters: levels, profiles and distribution.

PubMed

Ramu, Karri; Kajiwara, Natsuko; Tanabe, Shinsuke; Lam, Paul K S; Jefferson, Thomas A

2005-01-01

Polybrominated diphenyl ethers (PBDEs) and organochlorine compounds (OCs) were determined in the blubber, liver and kidney of Indo-Pacific humpback dolphins (Sousa chinensis) and finless porpoises (Neophocaena phocaenoides) stranded in Hong Kong coastal waters during 1995-2001. Among the organohalogen compounds analyzed, DDTs were the most dominant contaminants with concentrations ranging from 9.9 to 470 microg/g lipid wt. PBDEs in Hong Kong cetaceans, which are reported for the first time, were detected in all the samples with values ranging from 0.23 to 6.0 microg/g lipid wt., with a predominance of BDE-47. Results from this study suggest PBDEs should be classified as priority pollutants in Asia. Higher concentrations were found in humpback dolphins than in finless porpoises, and this was attributed mainly to differences in habitat. Elevated residues of PCBs and DDTs in some cetaceans suggest these species may be at risk.

Octopamine connects nutrient cues to lipid metabolism upon nutrient deprivation.

PubMed

Tao, Jun; Ma, Yi-Cheng; Yang, Zhong-Shan; Zou, Cheng-Gang; Zhang, Ke-Qin

2016-05-01

Starvation is probably the most common stressful situation in nature. In vertebrates, elevation of the biogenic amine norepinephrine levels is common during starvation. However, the precise role of norepinephrine in nutrient deprivation remains largely unknown. We report that in the free-living nematode Caenorhabditis elegans, up-regulation of the biosynthesis of octopamine, the invertebrate counterpart of norepinephrine, serves as a mechanism to adapt to starvation. During nutrient deprivation, the nuclear receptor DAF-12, known to sense nutritional cues, up-regulates the expression of tbh-1 that encodes tyramine β-hydroxylase, a key enzyme for octopamine biosynthesis, in the RIC neurons. Octopamine induces the expression of the lipase gene lips-6 via its receptor SER-3 in the intestine. LIPS-6, in turn, elicits lipid mobilization. Our findings reveal that octopamine acts as an endocrine regulator linking nutrient cues to lipolysis to maintain energy homeostasis, and suggest that such a mechanism may be evolutionally conserved in diverse organisms.

Changes on lipid peroxidation,enzymatic activities and gene expression in planarian (Dugesia japonica) following exposure to perfluorooctanoic acid.

PubMed

Yuan, Zuoqing; Miao, Zili; Gong, Xiaoning; Zhao, Baoying; Zhang, Yuanyuan; Ma, Hongdou; Zhang, Jianyong; Zhao, Bosheng

2017-11-01

We investigated perfluorooctanoic acid (PFOA)-induced stress response in planarians. We administered different concentrations of PFOA to planarians for up to 10 d. PFOA exposure resulted in significant concentration-dependent elevations in lipid peroxidation, glutathione S-transferase and caspase-3 protease activities, and a significant decline in glutathione peroxidase activities compared with control groups. Exposure to PFOA significantly up-regulated the heat shock proteins hsp70 and hsp90, and p53, and down-regulated hsp40 compared with controls. PFOA exposure also increased HSP70 protein levels, as demonstrated by western blot analysis. These alterations indicated that PFOA exposure induced a stress response and affected the regulation of oxidative stress, enzymatic activities and gene expression. These results suggest that these sensitive parameters, together with other biomarkers, could be used for evaluating toxicity, for ecological risk assessment of PFOA in freshwaters. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulation of fatty acid synthase degradation by concerted action of p38 MAP kinase, E3 ligase COP1, and SH2-tyrosine phosphatase Shp2.

PubMed

Yu, Jianxiu; Deng, Rong; Zhu, Helen H; Zhang, Sharon S; Zhu, Changhong; Montminy, Marc; Davis, Roger; Feng, Gen-Sheng

2013-02-08

The Src-homology 2 (SH2) domain-containing tyrosine phosphatase Shp2 has been known to regulate various signaling pathways triggered by receptor and cytoplasmic tyrosine kinases. Here we describe a novel function of Shp2 in control of lipid metabolism by mediating degradation of fatty acid synthase (FASN). p38-phosphorylated COP1 accumulates in the cytoplasm and subsequently binds FASN through Shp2 here as an adapter, leading to FASN-Shp2-COP1 complex formation and FASN degradation mediated by ubiquitination pathway. By fasting p38 is activated and stimulates FASN protein degradation in mice. Consistently, the FASN protein levels are dramatically elevated in mouse liver and pancreas in which Shp2/Ptpn11 is selectively deleted. Thus, this study identifies a new activity for Shp2 in lipid metabolism.

Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.

PubMed

Ferreira, Cláudia N; Carvalho, Maria G; Reis, Helton J; Gomes, Karina B; Sousa, Marinez O; Palotás, András

2014-05-01

Dyslipidemia is one of the pathognomonic elements of athero-genesis, as well as cerebro- and cardio-vascular disease (CCVD). Hemostatic factors are also involved in athero-sclerosis and ischemic changes, however their relationship with disrupted lipid homeostasis is not well characterized. The aim of this study was to determine the coagulation state of dyslipidemic patients and to evaluate their association with CCVD risk factors. Biochemical and hematological parameters, as well as neuro-psychiatric profile of 109 dyslipidemic subjects and 107 normo-lipidic healthy volunteers were assessed. Serum bio-marker levels and cognitive performance generally did not differ in the groups, but prothrombin fragment 1+2 (F1+2) and D-dimer concentrations were markedly higher among women. Hyper-coagulability was not associated with dyslipidemia, but was correlated with the female gender, which might pose an increased thromboembolic risk in asymptomatic women.

Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing

PubMed Central

Gehwolf, Renate; Wagner, Andrea; Lehner, Christine; Bradshaw, Amy D.; Scharler, Cornelia; Niestrawska, Justyna A.; Holzapfel, Gerhard A.; Bauer, Hans-Christian; Tempfer, Herbert; Traweger, Andreas

2016-01-01

Acute and chronic tendinopathies remain clinically challenging and tendons are predisposed to degeneration or injury with age. Despite the high prevalence of tendon disease in the elderly, our current understanding of the mechanisms underlying the age-dependent deterioration of tendon function remains very limited. Here, we show that Secreted protein acidic and rich in cysteine (Sparc) expression significantly decreases in healthy-aged mouse Achilles tendons. Loss of Sparc results in tendon collagen fibrillogenesis defects and Sparc−/− tendons are less able to withstand force in comparison with their respective wild type counterparts. On the cellular level, Sparc-null and healthy-aged tendon-derived cells exhibited a more contracted phenotype and an altered actin cytoskeleton. Additionally, an elevated expression of the adipogenic marker genes PPARγ and Cebpα with a concomitant increase in lipid deposits in aged and Sparc−/− tendons was observed. In summary, we propose that Sparc levels in tendons are critical for proper collagen fibril maturation and its age-related decrease, together with a change in ECM properties favors lipid accretion in tendons. PMID:27586416

PCSK9 and lipoprotein (a) levels are two predictors of coronary artery calcification in asymptomatic patients with familial hypercholesterolemia.

PubMed

Alonso, Rodrigo; Mata, Pedro; Muñiz, Ovidio; Fuentes-Jimenez, Francisco; Díaz, Jose Luis; Zambón, Daniel; Tomás, Marta; Martin, Cesar; Moyon, Thomas; Croyal, Mikaël; Thedrez, Aurélie; Lambert, Gilles

2016-11-01

We aimed to assess whether elevated PCSK9 and lipoprotein (a) [Lp(a)] levels associate with coronary artery calcification (CAC), a good marker of atherosclerosis burden, in asymptomatic familial hypercholesterolemia. We selected 161 molecularly defined FH patients treated with stable doses of statins for more than a year. CAC was measured using the Agatston method and quantified as categorical variable. Fasting plasma samples were collected and analyzed for lipids and lipoproteins. PCSK9 was measured by ELISA, Lp(a) and apolipoprotein (a) concentrations by inmunoturbidimetry and LC-MS/MS, respectively. Circulating PCSK9 levels were significantly reduced in patients without CAC (n = 63), compared to those with CAC (n = 99). Patients with the highest CAC scores (above 100) had the highest levels of circulating PCSK9 and Lp(a). In multivariable regression analyses, the main predictors for a positive CAC score was age and sex followed by circulating PCSK9 and Lp(a) levels. In statin treated asymptomatic FH patients, elevated PCSK9 and Lp(a) levels are independently associated with the presence and severity of CAC, a good predictor of coronary artery disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Organic matter composition and substrate diversity under elevated CO2 in the Mojave Desert

NASA Astrophysics Data System (ADS)

Tfaily, M. M.; Hess, N. J.; Koyama, A.; Evans, R. D.

2016-12-01

Little is known about how rising atmospheric CO2 concentration will impact long-term plant biomass or the dynamics of soil organic matter (SOM) in arid ecosystems. In this study, we investigated the change in the molecular composition of SOM by high resolution mass spectrometry after 10 years exposure to elevated atmospheric CO2 concentrations at the Nevada Desert FACE Facility. Samples were collected from soil profiles from 0 to 1m in 0.2m increments under the dominant evergreen shrub (Larrea tridentata). The differences in the composition of SOM were more evident in soils close to the surface and consistent with higher bulk soil organic carbon (C) and total nitrogen (N) concentrations under elevated than ambient CO2, reflecting increased net productivity of shrubs under elevated CO2, which could be attributed to increased litter input from above-ground biomass and/or shallow roots, root exudation and/or microbial residues. This was further supported by the significant increase in the abundance of amino sugars-, protein- and carbohydrate-like compounds. These compounds are involved in diverse pathways ranging from sugars and amino-acid metabolism to lipid biosynthesis. This indicates increased activity and metabolism under elevated CO2 and suggests that elevated CO2 have altered microbial C use patterns, reflecting changes in the quality and quantity of soil C inputs. A significant increase in the mineral-bound soil organic C was also observed in the surface soils under elevated CO2. This was accompanied by increased microbial residues as identified by mass spectrometry that supports microbial lipid analysis, and reflecting accelerated microbial turnover under elevated CO2. Fungal neutral lipid fatty acids (NLFA) abundance doubled under elevated CO2. When provided with excess labile compounds, such as root exudates, and with limited supply of nutrients, fungi assimilate the excess labile C and store it as NLFA likely contributing to increased total N concentrations. This was further supported by the presence of acetyl glucosamine, a typical amino sugar, present in the chitin of fungi, under elevated than ambient CO2. Our results suggest that arid ecosystems, limited by water, may have a different C storage potential under changing climates than other ecosystems that are limited by N or P.

Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Alters Mitochondrial Membrane Lipids

PubMed Central

Sandra, Ferry; Esposti, Mauro Degli; Ndebele, Kenneth; Gona, Philimon; Knight, David; Rosenquist, Magnus; Khosravi-Far, Roya

2010-01-01

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) has been shown to have selective antitumor activity. TRAIL induces ubiquitous pathways of cell death in which caspase activation is mediated either directly or via the release of apoptogenic factors from mitochondria; however, the precise components of the mitochondrial signaling pathway have not been well defined. Notably, mitochondria constitute an important target in overcoming resistance to TRAIL in many types of tumors. Bid is considered to be fundamental in engaging mitochondria during death receptor–mediated apoptosis, but this action is dependent on mitochondrial lipids. Here, we report that TRAIL signaling induces an alteration in mitochondrial membrane lipids, particularly cardiolipin. This occurs independently of caspase activation and primes mitochondrial membranes to the proapoptotic action of Bid. We unveil a link between TRAIL signaling and alteration of membrane lipid homeostasis that occurs in parallel to apical caspase activation but does not take over the mode of cell death because of the concurrent activation of caspase-8. In particular, TRAIL-induced alteration of mitochondrial lipids follows an imbalance in the cellular homeostasis of phosphatidylcholine, which results in an elevation in diacylglycerol (DAG). Elevated DAG in turn activates the δ isoform of phospholipid-dependent serine/threonine protein kinase C, which then accelerates the cleavage of caspase-8. We also show that preservation of phosphatidylcholine homeostasis by inhibition of lipid-degrading enzymes almost completely impedes the activation of pro-caspase-9 while scarcely changing the activation of caspase-8. PMID:16166305

Additive effects of dexamethasone and palmitate on hepatic lipid accumulation and secretion.

PubMed

Harasim-Symbor, Ewa; Konstantynowicz-Nowicka, Karolina; Chabowski, Adrian

2016-11-01

Synthetic and natural glucocorticoids are able to highly modify liver lipid metabolism, which is possibly associated with nonalcoholic fatty liver disease development. We have assessed the changes in lipid and sphingolipid contents in hepatocytes, lipid composition and saturation status as well as the expression of proteins involved in fatty acid transport after both dexamethasone and palmitate treatments. The experiments were conducted on primary rat hepatocytes, incubated with dexamethasone and/or palmitic acid during short (16 h) and prolonged (40 h) exposure. Intracellular and extracellular lipid and sphingolipid contents were assessed by gas liquid chromatography and high-performance liquid chromatography, respectively. The expression of selected proteins was estimated by Western blotting. Short and prolonged exposure to dexamethasone combined with palmitic acid resulted in increased expression of fatty acid transporters, which was subsequently reflected by excessive intracellular accumulation of triacylglycerols and ceramide. The expression of microsomal transfer protein and cassette transporter was also significantly increased after dexamethasone and palmitate treatment, which was in accordance with elevated extracellular lipid and sphingolipid contents. Our data showed additive effects of dexamethasone and palmitate on protein-dependent fatty acid uptake in primary hepatocytes, resulting in the increased accumulation of triacylglycerols and sphingolipids. Moreover, the combined treatment altered fatty acid composition and diminished triacylglycerols desaturation index. Importantly, we observed that additive effects on both increased microsomal transport protein expression as well as elevated export of triacylglycerols, which may be relevant as a liver protective mechanism. © 2016 Society for Endocrinology.

In vivo effects of polyunsaturated, monounsaturated, and saturated fatty acids on hepatic and peripheral insulin sensitivity.

PubMed

Pereira, Sandra; Breen, Danna M; Naassan, Anthony E; Wang, Penny Y T; Uchino, Hiroshi; Fantus, I George; Carpentier, André C; Gutierrez-Juarez, Roger; Brindley, David N; Lam, Tony K T; Giacca, Adria

2015-02-01

Free fatty acids (FFAs) cause insulin resistance and are often elevated in obesity. Chronic ingestion of diets rich in saturated fat induces more insulin resistance than diets rich in unsaturated fat, however, it remains unclear whether different FFAs cause distinct levels of insulin resistance in the short-term, which is relevant to the feeding and fasting cycle. Protein kinase C (PKC)-δ is implicated in hepatic insulin resistance. Therefore, we investigated the effects of short-term elevation of fatty acids with different degrees of unsaturation on hepatic insulin action and liver PKC-δ membrane translocation, a marker of activation. Triglyceride emulsions of Soybean Oil+Heparin (polyunsaturated (POLY)), Olive Oil+Heparin (monounsaturated (MONO)), Lard Oil+Heparin (saturated (SATU)), or saline (SAL) were infused intravenously for 7h to elevate plasma FFA concentrations ~3-4 fold in rats. During the last 2h of infusion, a hyperinsulinemic-euglycemic clamp with tritiated glucose methodology was performed to examine hepatic and peripheral insulin sensitivity. Surprisingly, SATU, MONO, and POLY impaired peripheral insulin sensitivity (glucose utilization divided by insulin) to a similar extent. Furthermore, all lipids induced a similar degree of hepatic insulin resistance compared to SAL. Although there were changes in hepatic content of lipid metabolites, there were no significant differences in liver PKC-δ membrane translocation across fat groups. In summary, in the short-term, FFAs with different degrees of unsaturation impair peripheral insulin sensitivity and induce hepatic insulin resistance as well as hepatic PKC-δ translocation to the same extent. Copyright © 2015 Elsevier Inc. All rights reserved.

Elevated seawater temperature, not pCO2, negatively affects post-spawning adult mussels (Mytilus edulis) under food limitation.

PubMed

Clements, Jeff C; Hicks, Carla; Tremblay, Réjan; Comeau, Luc A

2018-01-01

Pre-spawning blue mussels ( Mytilus edulis ) appear sensitive to elevated temperature and robust to elevated p CO 2 ; however, the effects of these stressors soon after investing energy into spawning remain unknown. Furthermore, while studies suggest that elevated p CO 2 affects the byssal attachment strength of Mytilus trossulus from southern latitudes, p CO 2 and temperature impacts on the byssus strength of other species at higher latitudes remain undocumented. In a 90 day laboratory experiment, we exposed post-spawning adult blue mussels ( M. edulis ) from Atlantic Canada to three p CO 2 levels ( p CO 2 ~625, 1295 and 2440 μatm) at two different temperatures (16°C and 22°C) and assessed energetic reserves on Day 90, byssal attachment strength on Days 30 and 60, and condition index and mortality on Days 30, 60 and 90. Results indicated that glycogen content was negatively affected under elevated temperature, but protein, lipid, and overall energy content were unaffected. Reduced glycogen content under elevated temperature was associated with reduced condition index, reduced byssal thread attachment strength, and increased mortality; elevated p CO 2 had no effects. Overall, these results suggest that the glycogen reserves of post-spawning adult M. edulis are sensitive to elevated temperature, and can result in reduced health and byssal attachment strength, leading to increased mortality. These results are similar to those reported for pre-spawning mussels and suggest that post-spawning blue mussels are tolerant to elevated p CO 2 and sensitive to elevated temperature. In contrast to previous studies, however, elevated pCO 2 did not affect byssus strength, suggesting that negative effects of elevated p CO 2 on byssus strength are not universal.