CE: Triglycerides: Do They Matter?

PubMed

Scordo, Kristine; Pickett, Kim Anne

2017-01-01

: Since the introduction of HMG-CoA reductase inhibitors, also known as statins, as an adjunct to diet in the treatment of hyperlipidemia and the greater emphasis placed on reducing low-density lipoprotein (LDL) cholesterol levels in the prevention of atherosclerosis and cardiovascular disease (CVD), there has been less focus on the value of lowering serum triglyceride levels. Many patients are aware of their "good" and "bad" cholesterol levels, but they may not be aware of their triglyceride level or of the association between high triglycerides and the development of CVD. In recent years, however, in light of the increasing incidences of obesity, insulin resistance, and type 2 diabetes, lowering triglyceride levels has gained renewed interest. In addition to the focus on lowering LDL cholesterol levels in CVD prevention, clinicians need to be aware of the role of triglycerides-their contribution to CVD, and the causes and treatment of hypertriglyceridemia.

Common variants associated with plasma triglycerides and risk for coronary artery disease

USDA-ARS?s Scientific Manuscript database

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common va...

Successful treatment of severe hypertriglyceridemia with a formula diet rich in omega-3 fatty acids and medium-chain triglycerides.

PubMed

Hauenschild, Annette; Bretzel, Reinhard G; Schnell-Kretschmer, Henning; Kloer, Hans-Ulrich; Hardt, Philip D; Ewald, Nils

2010-01-01

Patients with highly increased plasma triglyceride levels are at risk of developing serious complications such as pancreatitis, coronary heart disease and stroke. Therefore it is important to rapidly decrease plasma triglyceride levels. A sufficient control of triglyceride levels with drugs like fibrates, statins or nicotinic acid can usually only be attained after a couple of weeks. Plasma exchange appears to be a fast but expensive method to reduce triglyceride levels. In this study we describe the use of a new omega-3 fatty acid and medium-chain triglyceride-rich formula diet as a therapeutic concept to reduce plasma triglyceride levels fast and effectively. Thirty-two patients with severe hypertriglyceridemia were treated with the especially composed formula diet for a period of 7 days. Within this period of time, plasma triglycerides decreased from 1,601 (402-4,555) to 554 (142-2,382) mg/dl (p < 0.05). Total cholesterol levels were reduced from 417 (211-841) to 287 (165-457) mg/dl (p < 0.001). Fasting glucose and uric acid levels also slightly decreased (-8%; -12%). The formula diet as a 1-week treatment was well tolerated and accepted by the patients. This diet was successfully used as an acute treatment in severe hypertriglyceridemia and showed effectiveness in rapidly and safely lowering plasma triglyceride levels. (c) 2010 S. Karger AG, Basel.

The c.553G>T Genetic Variant of the APOA5 Gene and Altered Triglyceride Levels in the Asian Population: A Meta-Analysis of Case-Control Studies.

PubMed

He, Hongjuan; Lei, Lei; Chen, Erfei; Dong, Jing; Zhang, Kejin; Yang, Jin

2016-12-01

To explore the association of the APOA5 gene c.553G>T polymorphism with hypertriglyceridemia (HTG) susceptibility and altered triglyceride levels. We searched the PubMed, Google Scholar, and CNKI databases for published studies relating to analyses of these associations. Case-control and comparative studies of the association between the APOA5 c.553G>T variant and altered triglyceride levels were included. In total, the meta-analysis involved 10 studies on HTG, which provided 2219 cases and 3401 controls. To measure the correlation between the c.553G>T polymorphism and HTG susceptibility, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The overall OR was calculated using a random-effects model. Compared with APOA5 c.553 GG carriers, c.553T carriers displayed an increased risk of HTG in the Asian population, with an overall random effects OR of 3.55 (95% CI: 2.46-5.13) in the dominant model. There was significant heterogeneity among the studies (P heterogeneity : Chi 2  = 45.80, I 2  = 75.98%), which may be largely explained by certain patient types. Both the sensitivity analysis and publication bias suggested that the overall result was acceptable. Subgroup analysis showed a large difference in serum triglyceride levels based on the c.553 G > T polymorphism in healthy individuals and HTG patients. APOA5 c.553T carriers exhibit higher triglyceride levels than GG carriers. Our results suggest that APOA5 c. 553T is an independent risk factor for HTG and increased triglyceride levels in the Asian population. APOA5 c. 553T could be employed as a genetic risk marker for HTG and increased triglyceride levels.

Positive correlation between retinol binding protein 4 (RBP4) and triglyceride level in central obesity

NASA Astrophysics Data System (ADS)

Oktaria, S.; Sari, D. K.; Dalimunthe, D.; Eyanoer, P. C.

2018-03-01

Obesity has become an epidemic in both developed and developing countries. Central obesity considered a risk factor that is closely related to several chronic diseases. Central obesity is associated with elevated triglyceride levels and associated with RBP4 which can lead to insulin resistance. Increased level of RBP4 can cause lipid metabolism disorders and can become a marker for insulin resistance and metabolic syndrome. This study aims to find the correlation of RBP4 with triglycerides and Apo B100 in central obesity. It was a cross- sectional study on 46 subjects with central obesity, aged 20-50 years old. Blood samples were taken in cubital vein and examined for RBP4 and triglyceride levels. Data analysis was performed using Spearman correlation test. The results showed that gender frequency distribution showed little difference between men and women, i. e., men 43.5% and women 56.5%. RBP4 level was positively correlated with triglyceride (r = 0.48) and statistically significant (p = 0.001). The rbp4 level was positively correlated with triglyceride, indicating the role of RBP4 on high triglyceride level in central obesity.

Determining triglyceride reductions needed for clinical impact in severe hypertriglyceridemia.

PubMed

Christian, Jennifer B; Arondekar, Bhakti; Buysman, Erin K; Jacobson, Terry A; Snipes, Rose G; Horwitz, Ralph I

2014-01-01

Patients with severe hypertriglyceridemia have an increased risk of cardiovascular disease and pancreatitis. Target triglyceride levels associated with clinical benefit for patients with severe hypertriglyceridemia are not currently known. This study evaluates the association between lower follow-up triglyceride levels and incidence of clinical events for patients with severe hypertriglyceridemia. By using claims data from 2 large US healthcare databases, we conducted a retrospective cohort study and identified 41,210 adults with severe hypertriglyceridemia (triglycerides ≥ 500 mg/dL) between June 2001 and September 2010. The date of the first severe hypertriglyceridemia laboratory result was the index date. Patients were categorized into 1 of 5 triglyceride ranges (<200 mg/dL, 200-299 mg/dL, 300-399 mg/dL, 400-499 mg/dL, and ≥ 500 mg/dL) based on a follow-up triglyceride level assessed 6 to 24 weeks after initial triglyceride levels were measured. Adjusted Cox regression models were developed to evaluate the impact of follow-up triglyceride levels on rates of pancreatitis episodes and cardiovascular events. The mean age of patients was 50 years, 72% were male, and the mean follow-up was 825 days. Patients with severe hypertriglyceridemia with follow-up triglyceride levels <200 mg/dL experienced a lower rate of pancreatitis episodes (adjusted incidence rate ratio, 0.45; 95% confidence interval, 0.34-0.60) and cardiovascular events (adjusted incidence rate ratio, 0.71; 95% confidence interval, 0.64-0.78) with some clinical benefit in adults with severe hypertriglyceridemia with follow-up triglyceride levels 200 to 299 mg/dL and 300 to 399 mg/dL (P < .001 for trend). We observed the greatest impact on clinical events among patients with severe hypertriglyceridemia with the lowest follow-up triglyceride levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Two independent apolipoprotein a5 Haplotypes influence human plasma triglyceride levels

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

Pennacchio, Len A.; Olivier, Michael; Hubacek, Jaroslav A.

2002-09-16

The recently identified apolipoprotein A5 gene (APOA5) has been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. We previously identified an APOA5 haplotype (designated APOA5*2) that is present in {approx}16 percent of Caucasians and is associated with increased plasma triglyceride concentrations. In this report we describe another APOA5 haplotype (APOA5*3) containing the rare allele of the single nucleotide polymorphism c.56C>G that changes serine to tryptophan at codon 19 and is independently associated with high plasma triglyceride levels in three different populations. In a sample of 264 Caucasian men and women with plasma triglyceridemore » concentrations above the 90th percentile or below the 10th percentile, the APOA5*3 haplotype was more than three-fold more common in the group with high plasma triglyceride levels. In a second independently ascertained sample of Caucasian men and women (n 1/4 419) who were studied while consuming their self-selected diets as well as after high-carbohydrate diets and high-fat diets, the APOA5*3 haplotype was associated with increased plasma triglyceride levels on all three dietary regimens. In a third population comprising 2660 randomly selected individuals, the APOA5*3 haplotype was found in 12 percent of Caucasians, 14 percent of African-Americans and 28 percent of Hispanics and was associated with increased plasma triglyceride levels in both men and women in each ethnic group. These findings establish that the APOA5 locus contributes significantly to inter-individual variation in plasma triglyceride levels in humans. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 50 percent of African-Americans, Hispanics and Caucasians and support the contribution of common human variation to quantitative phenotypes in the general population.« less

Triglyceride level affecting shared susceptibility genes in metabolic syndrome and coronary artery disease.

PubMed

Kisfali, P; Polgár, N; Sáfrány, E; Sümegi, K; Melegh, B I; Bene, J; Wéber, A; Hetyésy, K; Melegh, B

2010-01-01

Metabolic syndrome is characterized primarily by abdominal obesity, high triglyceride- and low HDL cholesterol levels, elevated blood pressure, and increased fasting glucose levels, which are often associated with coronary heart diseases. Several factors, such as physical inactivity, age, and several endocrine and genetic factors can increase the risk of the development of the disease. Gathered evidence shows, that metabolic syndrome is not only a risk factor for cardiovascular disease, but often both of them have the same shared susceptibility genes, as several genetic variants have shown a predisposition to both diseases. Due to the spread of robust genome wide association studies, the number of candidate genes in metabolic syndrome and coronary heart disease susceptibility increases very rapidly. From the growing spectrum of the genes influencing lipid metabolism (like the LPL; PPARA; APOE; APOAI/CIII/AIV genecluster and APOAS5), the current review focuses on shared susceptibility variants involved in triglyceride metabolism and consequently the effects on the circulating triglyceride levels. As the elevated levels of triglycerides can be associated with disease phenotypes, some of these SNPs can have susceptibility features in both metabolic syndrome and in coronary heart disease, thereby some of them can even represent a kind of susceptibility link between metabolic syndrome and coronary artery disease.

Effects of stress on serum triglycerides, nonsterified fatty acids, and total cholesterol levels in male rats after ethanol administration

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

Hershock, D.; Vogel, W.H.

1989-02-09

Serum triglycerides, nonesterified fatty acids (NEFA), and total cholesterol were determined during one hour immobilization stress in adult male Sprague-Dawley rats after ethanol administration (2g/kg, i.p.). Stress and ethanol effects were evaluated in two experiments: (1) rats maintained on Purina Rodent Chow for six weeks and fasted for 24 hours; and (2) rats maintained on the same diet supplemented with 1% cholesterol and 10% peanut oil for six weeks and nonfasted prior to experimentation. Blood was obtained from indwelling jugular catheters. In each experiment, differences were seen in triglyceride and NEFA levels but not in total cholesterol. In the regularmore » diet-fed rats (1), serum triglyceride levels were not affected by either stress or ethanol. However, NEFA levels did show differences in the response to ethanol and stress. A 63% decrease from baseline after 5{prime} of stress was partially abolished by ethanol; instead, a 24% increase was observed. Also, a stress-induced increase in NEFA which occurred after 15{prime} was not observed in the ethanol treated rats; rather, a decrease in NEFA was noted. Total cholesterol did not change in response to stress or ethanol. In the high cholesterol diet-fed rats (2), ethanol did not suppress a stress-induced increase in triglyceride levels. NEFA levels in ethanol-treated rats were higher during the first 15{prime} of stress as compared to stress alone. A decrease in NEFA was however seen in the ethanol-treated rats after 30{prime} of stress and these levels remained lower than the stress alone group. A diet-induced increase in total cholesterol levels was observed; however, no changes were seen due to either or ethanol. Thus, ethanol administration prior to acute immobilization stress did affect serum triglyceride and NEFA levels but did not change total cholesterol.« less

Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians.

PubMed

AshokKumar, Manickaraj; Subhashini, Navaneethan Gnana Veera; SaiBabu, Ramineni; Ramesh, Arabandi; Cherian, Kotturathu Mammen; Emmanuel, Cyril

2010-01-01

Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction-restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.

Apolipoprotein A-V: a potential modulator of plasma triglyceride levels in Turks.

PubMed

Hodoglugil, Ugur; Tanyolaç, Sinan; Williamson, David W; Huang, Yadong; Mahley, Robert W

2006-01-01

The apolipoprotein A-V gene (APOA5) plays an important role in determining plasma triglyceride levels. We studied the effects of APOA5 polymorphisms on plasma triglyceride levels in Turks, a population with low levels of HDL cholesterol and a high prevalence of coronary artery disease. We found 15 polymorphisms, three of which were novel. Seven haplotype-tagging single nucleotide polymorphisms (SNPs) were chosen and genotyped in approximately 3,000 subjects. The rare alleles of the -1464T>C, -1131T>C, S19W, and 1259T>C SNPs were significantly associated with increased triglyceride levels (19-86 mg/dl; P < 0.05) and had clear gene-dose effects. Haplotype analysis of the nine common APOA5 haplotypes revealed significant effects on triglyceride levels (P < 0.001). Detailed analysis of haplotypes clearly showed that the -1464T>C polymorphism had no effect by itself but was a marker for the -1131T>C, S19W, and 1259T>C polymorphisms. The -1131T>C and 1259T>C polymorphisms were in a strong but incomplete linkage disequilibrium and appeared to have independent effects. Thus, the APOA5 -1131T>C, S19W, and 1259T>C rare alleles were associated with significant increases in plasma triglyceride levels. At least one of these alleles was present in approximately 40% of the Turks. Similar associations were observed for -1131T>C and S19W in white Americans living in San Francisco, California.

Acute Effects of Morning Light on Plasma Glucose and Triglycerides in Healthy Men and Men with Type 2 Diabetes.

PubMed

Versteeg, Ruth I; Stenvers, Dirk J; Visintainer, Dana; Linnenbank, Andre; Tanck, Michael W; Zwanenburg, Gooitzen; Smilde, Age K; Fliers, Eric; Kalsbeek, Andries; Serlie, Mireille J; la Fleur, Susanne E; Bisschop, Peter H

2017-04-01

Ambient light intensity is signaled directly to hypothalamic areas that regulate energy metabolism. Observational studies have shown associations between ambient light intensity and plasma glucose and lipid levels, but human data on the acute metabolic effects of light are scarce. Since light is the main signal indicating the onset of the diurnal phase of physical activity and food intake in humans, we hypothesized that bright light would affect glucose and lipid metabolism. Therefore, we determined the acute effects of bright light on plasma glucose and lipid concentrations in 2 randomized crossover trials: (1) in 8 healthy lean men and (2) in 8 obese men with type 2 diabetes. From 0730 h, subjects were exposed to either bright light (4000 lux) or dim light (10 lux) for 5 h. After 1 h of light exposure, subjects consumed a 600-kcal mixed meal. Primary endpoints were fasting and postprandial plasma glucose levels. In healthy men, bright light did not affect fasting or postprandial plasma glucose levels. However, bright light increased fasting and postprandial plasma triglycerides. In men with type 2 diabetes, bright light increased fasting and postprandial glucose levels. In men with type 2 diabetes, bright light did not affect fasting triglyceride levels but increased postprandial triglyceride levels. We show that ambient light intensity acutely affects human plasma glucose and triglyceride levels. Our findings warrant further research into the consequences of the metabolic effects of light for the diagnosis and prevention of hyperglycemia and dyslipidemia.

Plasma apolipoprotein C-III levels, triglycerides, and coronary artery calcification in type 2 diabetics.

PubMed

Qamar, Arman; Khetarpal, Sumeet A; Khera, Amit V; Qasim, Atif; Rader, Daniel J; Reilly, Muredach P

2015-08-01

Triglyceride-rich lipoproteins have emerged as causal risk factors for developing coronary heart disease independent of low-density lipoprotein cholesterol levels. Apolipoprotein C-III (ApoC-III) modulates triglyceride-rich lipoprotein metabolism through inhibition of lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. Mutations causing loss-of-function of ApoC-III lower triglycerides and reduce coronary heart disease risk, suggestive of a causal role for ApoC-III. Little data exist about the relationship of ApoC-III, triglycerides, and atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Here, we examined the relationships between plasma ApoC-III, triglycerides, and coronary artery calcification in patients with T2DM. Plasma ApoC-III levels were measured in a cross-sectional study of 1422 subjects with T2DM but without clinically manifest coronary heart disease. ApoC-III levels were positively associated with total cholesterol (Spearman r=0.36), triglycerides (r=0.59), low-density lipoprotein cholesterol (r=0.16), fasting glucose (r=0.16), and glycosylated hemoglobin (r=0.12; P<0.0001 for all). In age, sex, and race-adjusted analysis, ApoC-III levels were positively associated with coronary artery calcification (Tobit regression ratio, 1.78; 95% confidence interval, 1.27-2.50 per SD increase in ApoC-III; P<0.001). As expected for an intermediate mediator, these findings were attenuated when adjusted for both triglycerides (Tobit regression ratio, 1.43; 95% confidence interval, 0.94-2.18; P=0.086) and separately for very low-density lipoprotein cholesterol (Tobit regression ratio, 1.14; 95% confidence interval, 0.75-1.71; P=0.53). In persons with T2DM, increased plasma ApoC-III is associated with higher triglycerides, less favorable cardiometabolic phenotypes, and higher coronary artery calcification, a measure of subclinical atherosclerosis. Therapeutic inhibition of ApoC-III may thus be a novel strategy for reducing plasma triglyceride-rich lipoproteins and cardiovascular risk in T2DM. © 2015 American Heart Association, Inc.

The effect of increasing levels of fish oil-containing structured triglycerides on protein metabolism in parenterally fed rats stressed by burn plus endotoxin.

PubMed

Gollaher, C J; Fechner, K; Karlstad, M; Babayan, V K; Bistrian, B R

1993-01-01

This report investigates the effect of various levels of medium-chain/fish oil structured triglycerides on protein and energy metabolism in hypermetabolic rats. Male Sprague-Dawley rats (192 to 226 g) were continuously infused with isovolemic diets that provided 200 kcal/kg per day and 2 g of amino acid nitrogen per kilogram per day. The percentage of nonnitrogen calories as structured triglyceride was varied: no fat, 5%, 15%, or 30%. A 30% long-chain triglyceride diet was also provided as a control to compare the protein-sparing abilities of these two types of fat. Nitrogen excretion, plasma albumin, plasma triglycerides, and whole-body and liver and muscle protein kinetics were determined after 3 days of feeding. Whole-body protein breakdown, flux, and oxidation were similar in all groups. The 15% structured triglyceride diet maximized whole-body protein synthesis (p < .05). Liver fractional synthetic rate was significantly greater in animals receiving 5% of nonprotein calories as structured triglyceride (p < .05). Muscle fractional synthetic rate was unchanged. Plasma triglycerides were markedly elevated in the 30% structured triglyceride-fed rats. The 30% structured triglyceride diet maintained plasma albumin levels better than those diets containing no fat, 5% medium-chain triglyceride/fish oil structured triglyceride, or 30% long-chain triglycerides. Nitrogen excretion was lower in animals receiving 30% of nonnitrogen calories as a structured triglyceride than in those receiving 30% as long-chain triglycerides, but this difference did not reach statistical significance (p = .1). These data suggest that protein metabolism is optimized when structured triglyceride is provided at relatively low dietary fat intakes.

Relationship between serum levels of triglycerides and vascular inflammation, measured as COX-2, in arteries from diabetic patients: a translational study

PubMed Central

2013-01-01

Background Inflammation is a common feature in the majority of cardiovascular disease, including Diabetes Mellitus (DM). Levels of pro-inflammatory markers have been found in increasing levels in serum from diabetic patients (DP). Moreover, levels of Cyclooxygenase-2 (COX-2) are increased in coronary arteries from DP. Methods Through a cross-sectional design, patients who underwent CABG were recruited. Vascular smooth muscle cells (VSMC) were cultured and COX-2 was measured by western blot. Biochemical and clinical data were collected from the medical record and by blood testing. COX-2 expression was analyzed in internal mammary artery cross-sections by confocal microscopy. Eventually, PGI2 and PGE2 were assessed from VSMC conditioned media by ELISA. Results Only a high glucose concentration, but a physiological concentration of triglycerides exposure of cultured human VSMC derived from non-diabetic patients increased COX-2 expression .Diabetic patients showed increasing serum levels of glucose, Hb1ac and triglycerides. The bivariate analysis of the variables showed that triglycerides was positively correlated with the expression of COX-2 in internal mammary arteries from patients (r2 = 0.214, P < 0.04). Conclusions We conclude that is not the glucose blood levels but the triglicerydes leves what increases the expression of COX-2 in arteries from DP. PMID:23642086

Association of SNP3 polymorphism in the apolipoprotein A-V gene with plasma triglyceride level in Tunisian type 2 diabetes

PubMed Central

Chaaba, Raja; Attia, Nebil; Hammami, Sonia; Smaoui, Maha; Mahjoub, Sylvia; Hammami, Mohamed; Masmoudi, Ahmed Slaheddine

2005-01-01

Background Apolipoprotein A-V (Apo A-V) gene has recently been identified as a new apolipoprotein involved in triglyceride metabolism. A single nucleotide polymorphism (SNP3) located in the gene promoter (-1131) was associated with triglyceride variation in healthy subjects. In type 2 diabetes the triglyceride level increased compared to healthy subjects. Hypertriglyceridemia is a risk factor for coronary artery disease. We aimed to examine the interaction between SNP3 and lipid profile and coronary artery disease (CAD) in Tunisian type 2 diabetic patients. Results The genotype frequencies of T/T, T/C and C/C were 0.74, 0.23 and 0.03 respectively in non diabetic subjects, 0.71, 0.25 and 0.04 respectively in type 2 diabetic patients. Triglyceride level was higher in heterozygous genotype (-1131 T/C) of apo A-V (p = 0.024). Heterozygous genotype is more frequent in high triglyceride group (40.9%) than in low triglyceride group (18.8%) ; p = 0.011. Despite the relation between CAD and hypertriglyceridemia the SNP 3 was not associated with CAD. Conclusion In type 2 diabetic patients SNP3 is associated with triglyceride level, however there was no association between SNP3 and coronary artery disease. PMID:15636639

Triglycerides and carotid intima-media thickness in ischemic stroke patients.

PubMed

Batluk, Jana; Leonards, Christopher O; Grittner, Ulrike; Lange, Kristin Sophie; Schreiber, Stephan J; Endres, Matthias; Ebinger, Martin

2015-11-01

Common carotid artery intima-media thickness (CCA-IMT) is an established marker for atherosclerosis. The role of triglycerides in CCA-IMT remains controversial. We sought to determine if elevated fasting and post-challenge triglycerides are associated with CCA-IMT. All acute ischemic stroke patients who participated in the Berlin "Cream & Sugar" study in the Charité Virchow and Charité Mitte Campuses between January 2009 and January 2014 and underwent carotid artery ultrasound studies were eligible for inclusion. A combined oral glucose and triglyceride tolerance test was performed 3-7 days after first ever ischemic stroke. Patients were classified according to triglyceride metabolism-namely, (1) patients reaching a maximum triglyceride levels 3 h post-challenge ("fast metabolizers," n = 37), (2) patients with increasing triglycerides 4 (medium metabolizers, n = 64), and (3) 5 h post-challenge ("slow metabolizers," n = 44; 13 missing). We included 158 patients (34% female; mean age 63 years, SD 14). Absolute non-fasting triglyceride levels were positively associated with CCA-IMT. A final multiple regression model revealed that older age, more severe strokes, and higher levels of fasting triglycerides were significantly and independently associated with higher mean CCA-IMT. Older age, higher waist-to-hip ratio, and higher levels of thyroid-stimulating hormone were independently associated with higher maximum CCA-IMT. Fasting triglycerides but not post-challenge triglycerides associate with CCA-IMT. An oral fat challenge may not add information on atherosclerotic status in ischemic stroke patients. The Berlin "Cream & Sugar" study is registered with EudraCT (2009-010356-97) and clinicaltrials.gov (NCT 01378468). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Stimulation of insulin secretion by medium-chain triglycerides in patients with cirrhosis 1

PubMed Central

McCullough, Frank S.; Tzagournis, Manuel; Greenberger, Norton J.; Linscheer, Willem G.

1971-01-01

Oral medium-chain triglycerides were given to 10 normal volunteers, 12 cirrhotics (group I) without and 28 cirrhotics (group II) with abnormal portal systemic communications (ascites, splenomegaly, oesophageal varices, or surgically-created portacaval shunts). After 30 ml of medium-chain triglyceride oil there was no appreciable change in serum glucose levels in any of the three groups nor in serum insulin levels in the normals and in cirrhotics in group I. However, there was a significant increase in serum insulin levels in the cirrhotic patients in group II. It is suggested that the rise in serum insulin levels after medium-chain triglycerides noted in the cirrhotics with shunts is due to shunting of insulin-containing portal blood around the liver (anatomical shunts) and to a diminished hepatic cell mass capable of extracting insulin (functional shunt). This differential response of serum insulin levels to medium-chain triglycerides may prove to be of value in detecting the presence of abnormal portal systemic communications in cirrhotic patients. PMID:5548559

Associations of triglyceride levels with longevity and frailty: A Mendelian randomization analysis

PubMed Central

Liu, Zuyun; Burgess, Stephen; Wang, Zhengdong; Deng, Wan; Chu, Xuefeng; Cai, Jian; Zhu, Yinsheng; Shi, Jianming; Xie, Xuejuan; Wang, Yong; Jin, Li; Wang, Xiaofeng

2017-01-01

Observational studies suggest associations of triglyceride levels with longevity and frailty. This study aimed to test whether the associations are causal. We used data from the Rugao Longevity and Ageing Study, a population-based cohort study performed in Rugao, China. A variant in the APOA5 gene region (rs662799) was used as the genetic instrument. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted triglycerides with two ageing phenotypes – longevity ( ≥95 years) and frailty (modified Fried frailty phenotype and Rockwood frailty index). C allele of rs662799 was robustly associated with higher triglyceride levels in the comparison group (β = 0.301 mmol/L per allele, p < 0.001), with an F statistic of 95.3 and R2 = 0.040. However MR analysis did not provide strong evidence for an association between genetically predicted triglyceride levels and probability of longevity (OR: 0.61; 95% CI: 0.35, 1.07 per 1 mmol/L increase in triglycerides). In the ageing arm (70–84 years), genetically predicted triglyceride levels were not associated with the frailty index (β = 0.008; 95% CI: −0.013, 0.029) or the frailty phenotype (OR: 1.91; 95% CI: 0.84, 4.37). In conclusion, there is currently a lack of sufficient evidence to support causal associations of triglyceride levels with longevity and frailty in elderly populations. PMID:28134330

The effect of bacterial sepsis severity on triglyceride value

NASA Astrophysics Data System (ADS)

Fahila, R.; Kembaren, T.; Rahimi, A.

2018-03-01

Sepsis can increase the amount of triglyceride as well as change the functional and structural components of lipoproteins. The triglyceride level is directly proportional to the severity of sepsis and associated with a systemic inflammatory response. The study aims to determine the correlation between the severity of bacterial sepsis with triglyceride value. An observational study with case control design from January2017 to March 2017 in 30 sepsis and 30 non-sepsis patients at H. Adam Malik General Hospital Medan. We examined Procalcitonin (PCT) and triglyceride level on the 1st, 3rd and 5th day and then analyzed using MannWhitney to assess their correlation.The triglyceride value in the sepsis group was 120 ± 5.1 mg/dl on day 1, non-sepsis 117.53 ± 36.37mg/dl. However, on the fifth day, the sepsis group of triglyceride values was 124.2±50.29mg/dl and the non-sepsis group triglyceride values 134.03±68.12mg/dl. There was no specific connection between the severity of sepsis and triglyceride value in a patient with sepsis.

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

PubMed

Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin, in patients.

TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models

PubMed Central

Tsushima, Yu; Tamura, Azusa; Hasebe, Makiko; Kanou, Masanobu; Kato, Hirotsugu; Kobayashi, Tsunefumi

2017-01-01

Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues. TMG-123 selectively activated GK enzyme activity without increasing Vmax. TMG-123 improved glucose tolerance without increasing plasma insulin levels in both insulin-deficient (Goto-Kakizaki rats) and insulin-resistant (db/db mice) models. The beneficial effect on glucose tolerance was greater than results observed with clinically available antidiabetic drugs such as metformin and glibenclamide in Zucker Diabetic Fatty rats. TMG-123 also improved glucose tolerance in combination with metformin. After 4 weeks of administration, TMG-123 reduced the Hemoglobin A1c levels without affecting liver and plasma triglyceride levels in Goto-Kakizaki rats and Diet-Induced Obesity mice. Moreover, TMG-123 sustained its effect on Hemoglobin A1c levels even after 24 weeks of administration without affecting triglycerides. Taken together, these data indicate that TMG-123 exerts glucose-lowering effects in both insulin-deficient and -resistant diabetes, and sustains reduced Hemoglobin A1c levels without affecting hepatic and plasma triglycerides even after chronic treatment. Therefore, TMG-123 is expected to be an antidiabetic drug that overcomes the concerns previously reported with other GK activators. PMID:28207836

TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models.

PubMed

Tsumura, Yoshinori; Tsushima, Yu; Tamura, Azusa; Hasebe, Makiko; Kanou, Masanobu; Kato, Hirotsugu; Kobayashi, Tsunefumi

2017-01-01

Glucokinase (GK) plays a critical role for maintaining glucose homeostasis with regulating glucose uptake in liver and insulin secretion in pancreas. GK activators have been reported to decrease blood glucose levels in patients with type 2 diabetes mellitus. However, clinical development of GK activators has failed due to the loss of glucose-lowering effects and increased plasma triglyceride levels after chronic treatment. Here, we generated a novel GK activator, TMG-123, examined its in vitro and in vivo pharmacological characteristics, and evaluated its risks of aforementioned clinical issues. TMG-123 selectively activated GK enzyme activity without increasing Vmax. TMG-123 improved glucose tolerance without increasing plasma insulin levels in both insulin-deficient (Goto-Kakizaki rats) and insulin-resistant (db/db mice) models. The beneficial effect on glucose tolerance was greater than results observed with clinically available antidiabetic drugs such as metformin and glibenclamide in Zucker Diabetic Fatty rats. TMG-123 also improved glucose tolerance in combination with metformin. After 4 weeks of administration, TMG-123 reduced the Hemoglobin A1c levels without affecting liver and plasma triglyceride levels in Goto-Kakizaki rats and Diet-Induced Obesity mice. Moreover, TMG-123 sustained its effect on Hemoglobin A1c levels even after 24 weeks of administration without affecting triglycerides. Taken together, these data indicate that TMG-123 exerts glucose-lowering effects in both insulin-deficient and -resistant diabetes, and sustains reduced Hemoglobin A1c levels without affecting hepatic and plasma triglycerides even after chronic treatment. Therefore, TMG-123 is expected to be an antidiabetic drug that overcomes the concerns previously reported with other GK activators.

Lipid Molecular Species Composition in Developing Soybean Cotyledons 1

PubMed Central

Wilson, Richard F.; Rinne, Robert W.

1978-01-01

The fatty acid composition of triglyceride and phospholipids in developing soybean cotyledons (Glycine max L., var. “Harosoy 63”) was analyzed at several stages of growth between 30 and 70 days after flowering. Changes observed in fatty acid composition within each lipid class were related to the levels of lipid molecular species present in the oil. Thirteen molecular species of triglyceride were identified in developing cotyledons, however three of these groups: trilinolenic, dilinolenic-monolinoleic, and linolenic-linoleic-oleic triglycerides, were not found in the mature seed. In immature cotyledons, trioleic and trilinoleic triglycerides accounted for 50% of the structures found; the level of these molecules decreased to 24.9% in the mature seed. The dilinoleic-monolinolenic triglycerides increased from 0.4 to 23.4% during cotyledon development. Changes in triglyceride composition were compared to the levels of molecular species for each phospholipid class. Dilinoleic and monosaturated monolinoleic phospholipid species were dominant in all phospholipid classes throughout development. PMID:16660395

Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction.

PubMed

Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; West, Anders Sode; Grande, Peer; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

2013-06-01

Elevated non-fasting triglycerides mark elevated levels of remnant cholesterol. Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene (APOA5) associates with an increased risk of myocardial infarction (MI). We resequenced the core promoter and coding regions of APOA5 in individuals with the lowest 1% (n = 95) and highest 2% (n = 190) triglyceride levels in the Copenhagen City Heart Study (CCHS, n = 10 391). Genetic variants which differed in frequency between the two extreme triglyceride groups (c.-1131T > C, S19W, and c.*31C > T; P-value: 0.06 to <0.001), thus suggesting an effect on triglyceride levels, were genotyped in the Copenhagen General Population Study (CGPS), the CCHS, and the Copenhagen Ischemic Heart Disease Study (CIHDS), comprising a total of 5705 MI cases and 54 408 controls. Genotype combinations of these common variants associated with increases in non-fasting triglycerides and calculated remnant cholesterol of, respectively, up to 68% (1.10 mmol/L) and 56% (0.40 mmol/L) (P < 0.001), and with a corresponding odds ratio for MI of 1.87 (95% confidence interval: 1.25-2.81). Using APOA5 genotypes in instrumental variable analysis, the observational hazard ratio for a doubling in non-fasting triglycerides was 1.57 (1.32-2.68) compared with a causal genetic odds ratio of 1.94 (1.40-1.85) (P for comparison = 0.28). For calculated remnant cholesterol, the corresponding values were 1.67(1.38-2.02) observational and 2.23(1.48-3.35) causal (P for comparison = 0.21). These data are consistent with a causal association between elevated levels of remnant cholesterol in hypertriglyceridaemia and an increased risk of MI. Limitations include that remnants were not measured directly, and that APOA5 genetic variants may influence other lipoprotein parameters.

Acute Effects of Morning Light on Plasma Glucose and Triglycerides in Healthy Men and Men with Type 2 Diabetes

PubMed Central

Versteeg, Ruth I.; Stenvers, Dirk J.; Visintainer, Dana; Linnenbank, Andre; Tanck, Michael W.; Zwanenburg, Gooitzen; Smilde, Age K.; Fliers, Eric; Kalsbeek, Andries; Serlie, Mireille J.; la Fleur, Susanne E.; Bisschop, Peter H.

2017-01-01

Ambient light intensity is signaled directly to hypothalamic areas that regulate energy metabolism. Observational studies have shown associations between ambient light intensity and plasma glucose and lipid levels, but human data on the acute metabolic effects of light are scarce. Since light is the main signal indicating the onset of the diurnal phase of physical activity and food intake in humans, we hypothesized that bright light would affect glucose and lipid metabolism. Therefore, we determined the acute effects of bright light on plasma glucose and lipid concentrations in 2 randomized crossover trials: (1) in 8 healthy lean men and (2) in 8 obese men with type 2 diabetes. From 0730 h, subjects were exposed to either bright light (4000 lux) or dim light (10 lux) for 5 h. After 1 h of light exposure, subjects consumed a 600-kcal mixed meal. Primary endpoints were fasting and postprandial plasma glucose levels. In healthy men, bright light did not affect fasting or postprandial plasma glucose levels. However, bright light increased fasting and postprandial plasma triglycerides. In men with type 2 diabetes, bright light increased fasting and postprandial glucose levels. In men with type 2 diabetes, bright light did not affect fasting triglyceride levels but increased postprandial triglyceride levels. We show that ambient light intensity acutely affects human plasma glucose and triglyceride levels. Our findings warrant further research into the consequences of the metabolic effects of light for the diagnosis and prevention of hyperglycemia and dyslipidemia. PMID:28470119

Flyway-scale variation in plasma triglyceride levels as an index of refueling rate in spring-migrating western sandpipers (Calidris mauri)

USGS Publications Warehouse

Williams, T.D.; Warnock, N.; Takekawa, John Y.; Bishop, M.A.

2007-01-01

We combined radiotelemetry, plasma metabolite analyses, and macro-invertebrate prey sampling to investigate variation in putative fattening rates (estimated as plasma triglyceride levels) at the flyway scale in Western Sandpipers (Calidris mauri) migrating between Punta Banda, Mexico (31°N), and Hartney Bay, Alaska (60°N), a distance of 4,240 km. Birds were caught at a wintering site (San Francisco Bay) and eight stopover sites along this Pacific Flyway. Body mass was higher in females than in males at six sites, but variation was not correlated with latitude for either sex, and the relationship of change in mass by date within sites was uninformative with regard to possible latitudinal variation in fattening rates. At San Francisco Bay, triglyceride levels were higher in the spring than in the winter. Mean plasma triglyceride varied among stopover sites, and there was a significant linear trend of increasing triglyceride levels with latitude as birds migrated north. At San Francisco Bay, length of stay was negatively related to triglyceride levels. However, plasma triglyceride levels at wintering or initial stopover sites (San Francisco and Punta Banda) did not predict individual variation in subsequent rates of travel during migration. We found no significant relationship between triglyceride levels and prey biomass at different stopover sites, which suggests that the latitudinal pattern is not explained by latitudinal changes in food availability. Rather, we suggest that differences in physiology of migratory birds at southern versus northern stopover sites or behavioral differences may allow birds to sustain higher fattening rates closer to the breeding grounds.

Effects of a 3-year dietary intervention on age-related changes in triglyceride and apolipoprotein A-V levels in patients with impaired fasting glucose or new-onset type 2 diabetes as a function of the APOA5 -1131 T > C polymorphism.

PubMed

Kim, Minjoo; Chae, Jey Sook; Kim, Miri; Lee, Sang-Hyun; Lee, Jong Ho

2014-04-28

The purpose of this study was to estimate the effects of a 3-year dietary intervention on age-related changes in triglyceride and apolipoprotein (apo A-V) levels in patients with impaired fasting glucose (IFG) or new-onset type 2 diabetes as a function of the APOA5 -1131 T > C polymorphism. We genotyped the APOA5 -1131 T > C polymorphism in 203 Korean individuals with IFG or new-onset type 2 diabetes for the TT (n = 91), TC (n = 98), and CC (n = 14) alleles. Plasma apo A-V and triglyceride levels were evaluated at baseline and after a 3-year dietary intervention. Our results showed that HDL, glucose, insulin, HOMA-IR index, free fatty acids, and apo A-V decreased and brachial-ankle pulse wave velocity (ba-PWV) and malondialdehyde (MDA) increased at the 3-year follow-up visit compared with baseline. Plasma apo A-V levels were reduced in subjects with the C allele (TC or CC) (P = 0.036) and triglyceride levels were reduced in subjects with the TT allele (P = 0.047). Subjects with the C allele showed lower post-treatment apo A-V and higher post-treatment fasting triglyceride levels than subjects with the TT allele. Changes in apo A-V and triglyceride levels were negatively correlated in subjects with the TT allele and positively correlated in subjects with the C allele. This study showed that the dietary intervention prevented an age-related increase in triglyceride levels in individuals with IFG or new-onset type 2 diabetes who possess the TT allele, but not the CT or CC allele, of the APOA5 -1131 T > C polymorphism.

Effects of a 3-year dietary intervention on age-related changes in triglyceride and apolipoprotein A-V levels in patients with impaired fasting glucose or new-onset type 2 diabetes as a function of the APOA5 -1131 T > C polymorphism

PubMed Central

2014-01-01

Background The purpose of this study was to estimate the effects of a 3-year dietary intervention on age-related changes in triglyceride and apolipoprotein (apo A-V) levels in patients with impaired fasting glucose (IFG) or new-onset type 2 diabetes as a function of the APOA5 -1131 T > C polymorphism. Methods We genotyped the APOA5 -1131 T > C polymorphism in 203 Korean individuals with IFG or new-onset type 2 diabetes for the TT (n = 91), TC (n = 98), and CC (n = 14) alleles. Plasma apo A-V and triglyceride levels were evaluated at baseline and after a 3-year dietary intervention. Results Our results showed that HDL, glucose, insulin, HOMA-IR index, free fatty acids, and apo A-V decreased and brachial-ankle pulse wave velocity (ba-PWV) and malondialdehyde (MDA) increased at the 3-year follow-up visit compared with baseline. Plasma apo A-V levels were reduced in subjects with the C allele (TC or CC) (P = 0.036) and triglyceride levels were reduced in subjects with the TT allele (P = 0.047). Subjects with the C allele showed lower post-treatment apo A-V and higher post-treatment fasting triglyceride levels than subjects with the TT allele. Changes in apo A-V and triglyceride levels were negatively correlated in subjects with the TT allele and positively correlated in subjects with the C allele. Conclusions This study showed that the dietary intervention prevented an age-related increase in triglyceride levels in individuals with IFG or new-onset type 2 diabetes who possess the TT allele, but not the CT or CC allele, of the APOA5 -1131 T > C polymorphism. PMID:24775272

Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes: subanalysis of the Japan Diabetes Complications Study (JDCS).

PubMed

Sone, Hirohito; Tanaka, Sachiko; Tanaka, Shiro; Iimuro, Satoshi; Oida, Koji; Yamasaki, Yoshimitsu; Oikawa, Shinichi; Ishibashi, Shun; Katayama, Shigehiro; Ohashi, Yasuo; Akanuma, Yasuo; Yamada, Nobuhiro

2011-11-01

Risk factors for cardiovascular complications in Japanese patients with diabetes have not been fully elucidated. Our objective was to determine incidence of and risk factors for coronary heart disease (CHD) and stroke in Japanese diabetic patients. We conducted a prospective study at 59 hospitals throughout Japan. Patients included 940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history of cardiovascular complications who were followed for a median of 7.86 yr. This was an observational study. Incidence of CHD and stroke was evaluated. Incidences of CHD and stroke per 1000 person-years were 9.59 and 7.45, respectively, whereas those of myocardial and brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis revealed that the serum log-transformed triglyceride level was a potent and independent predictor of CHD [hazard ratio (HR) = 1.54; 95% confidence interval (CI) = 1.22-1.94 per 1 sd increase), comparable to low-density lipoprotein (LDL) cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 sd increase). Triglycerides and LDL cholesterol linearly and continuously increased CHD risk, and subjects in the top third for both had markedly high risks of CHD, and their effects were possibly additive. However, serum triglycerides worked independently of blood pressure levels. Systolic blood pressure was the only significant predictor for stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 sd increase). In Japanese patients with type 2 diabetes, the serum triglyceride level was a leading predictor of CHD, comparable to LDL cholesterol. Because the serum triglyceride level is not a leading predictor of CHD in diabetic subjects in Western countries, ethnic group-specific strategies for prevention of diabetic macroangiopathy may be indicated.

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

Association of ADRB2 polymorphism with triglyceride levels in Tongans.

PubMed

Naka, Izumi; Ohashi, Jun; Kimura, Ryosuke; Inaoka, Tsukasa; Matsumura, Yasuhiro

2013-07-23

Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index.

Targeting APOC3 in the familial chylomicronemia syndrome.

PubMed

Gaudet, Daniel; Brisson, Diane; Tremblay, Karine; Alexander, Veronica J; Singleton, Walter; Hughes, Steven G; Geary, Richard S; Baker, Brenda F; Graham, Mark J; Crooke, Rosanne M; Witztum, Joseph L

2014-12-04

The familial chylomicronemia syndrome is a genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis due to a deficiency in lipoprotein lipase (LPL). Currently, there are no effective therapies except for extreme restriction in the consumption of dietary fat. Apolipoprotein C-III (APOC3) is known to inhibit LPL, although there is also evidence that APOC3 increases the level of plasma triglycerides through an LPL-independent mechanism. We administered an inhibitor of APOC3 messenger RNA (mRNA), called ISIS 304801, to treat three patients with the familial chylomicronemia syndrome and triglyceride levels ranging from 1406 to 2083 mg per deciliter (15.9 to 23.5 mmol per liter). After 13 weeks of study-drug administration, plasma APOC3 levels were reduced by 71 to 90% and triglyceride levels by 56 to 86%. During the study, all patients had a triglyceride level of less than 500 mg per deciliter (5.7 mmol per liter) with treatment. These data support the role of APOC3 as a key regulator of LPL-independent pathways of triglyceride metabolism.

Interactive effects of C-reactive protein levels on the association between APOE variants and triglyceride levels in a Taiwanese population.

PubMed

Wu, Semon; Hsu, Lung-An; Teng, Ming-Sheng; Lin, Jeng-Feng; Chou, Hsin-Hua; Lee, Ming-Cheng; Wu, Yi-Ming; Su, Cheng-Wen; Ko, Yu-Lin

2016-05-13

Apolipoprotein E (APOE) plays a major role in lipid metabolism and inflammation. However, the association between APOE gene polymorphisms and serum triglyceride levels remains controversial. We tested the effects of APOE variants on triglyceride levels and their interactions with the inflammatory marker C-reactive protein (CRP) in a Taiwanese population. Two APOE single nucleotide polymorphisms (SNPs) rs429358 and rs7412 were genotyped by TaqMan Assay using real time PCR in 595 healthy subjects attending the clinic for routine visits. After adjustment for clinical covariates, subjects carrying the rs429358-TT genotype and non-ε4 alleles were found to have higher CRP levels, whereas those with rs7412-CC genotype and non-ε2 alleles had significantly higher total and low-density lipoprotein cholesterol levels (all P < 0.01). Using subgroup and interaction analyses, we observed significantly lower triglyceride levels in subjects carrying the rs429358-TT genotype and non-ε4 alleles in the low CRP group (P = 2.71 × 10(-4) and P = 4.32 × 10(-4), respectively), but not in those in the high CRP group (interaction P = 0.013 and 0.045, respectively). In addition, multivariate stepwise linear regression analysis showed that subjects carrying the rs429358-TT genotype and non-ε4 alleles with low CRP levels had significantly lower triglyceride levels (P < 0.001 and P < 0.001, respectively). In addition, when combined with the risk alleles of GCKR, APOA5 and LPL gene variants, we observed that triglyceride levels increased significantly with the number of risk alleles (P = 2.9 × 10(-12)). The combination of SNPs and ε alleles at the APOE locus is involved in managing lipid and CRP levels in the Taiwanese population. APOE polymorphisms interact with CRP to regulate triglyceride levels, thus triglyceride concentration is influenced by both the genetic background of the APOE locus and the inflammatory status of a subject.

Stepwise positive association between APOA5 minor allele frequencies and increasing plasma triglyceride quartiles in random patients with hypertriglyceridemia of unclarified origin.

PubMed

Hadarits, Ferenc; Kisfali, Péter; Mohás, Márton; Maász, Anita; Sümegi, Katalin; Szabó, Melinda; Hetyésy, Katalin; Valasek, Andrea; Janicsek, Ingrid; Wittmann, István; Melegh, Béla

2011-03-01

Apolipoprotein A5 (ApoA5) gene and its protein product play a central role in the complex regulation of circulating triglyceride levels in humans. Naturally occurring variants of the apolipoprotein A5 gene have been associated with increased triglyceride levels and have been found to confer risk for cardiovascular diseases. In our study, four polymorphisms, the T-1131C, IVS3+G476A, T1259C, and C56G alleles of APOA5 were analyzed in a total of 436 patients by polymerase chain reaction-restriction fragment length polymorphism methods. The randomly selected patients were classified into four quartile (q) groups based on triglyceride levels (q1: TG<1.31 mmol/l; q2: 1.31-2.90 mmol/l; q3: 2.91-4.85 mmol/l; q4: TG>4.85 mmol/l). We observed significant stepwise increasing association between the four APOA5 minor allele carrier frequencies and plasma triglyceride quartiles: -1131C (q1: 4.44%; q2: 8.95%; q3: 12.9%; q4: 20.6%), IVS3 + 476A (q1: 4.44%; q2: 5.79%; q3: 11.1%; q4: 19.7%), 1259C (q1: 4.44%; q2: 6.84%; q3: 11.1%; q4: 20.6%) and 56G (q1: 5.64%; q2: 6.31%; q3: 11.16%; q4: 11.9%). The serum total cholesterol and high density lipoprotein-cholesterol levels also showed allele-dependent differences in the quartiles. The findings presented here revealed a special arrangement of APOA5 minor alleles in patients with different serum triglyceride ranges in Hungarians.

Two meals with different carbohydrate, fat and protein contents render equivalent postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin.

PubMed

Ohlsson, Bodil; Darwiche, Gassan; Roth, Bodil; Höglund, Peter

2016-11-01

The aim was to compare postprandial plasma levels of calprotectin, cortisol, triglycerides and zonulin between a control breakfast and a moderately low-carbohydrate test breakfast, given randomly after 10-h fast. Blood samples were collected before and repeatedly after the meal. Plasma calprotectin, cortisol, triglycerides and zonulin were analyzed. The total area under the curve (tAUC) and change in AUC from baseline (dAUC) were calculated. Ratios between the test and control values were calculated to investigate equivalence. Healthy volunteers (8 men and 12 women; 46.0 ± 14.5 years) were included. tAUCs of cortisol and triglycerides did not differ between the breakfasts (p = 0.158 versus p = 0.579). Cortisol dAUCs were decreased and triglyceride dAUCs were increased after both breakfasts, with no differences between the breakfasts (p = 0.933 versus p = 0.277). Calprotectin and zonulin levels were unaffected. The meals were bioequivalent for cortisol, triglycerides and zonulin, but not for calprotectin.

[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.

Increased serum triglycerides and reduced HDL cholesterol in male rats after intake of ammonium chloride for 3 weeks

PubMed Central

2013-01-01

Background Previous data suggested that intake of sodas and other acid beverages might be associated with increased levels of serum triglycerides, lowered HDL cholesterol, and increased formation of mono unsaturated fatty acids, which are the preferred ones for triglyceride synthesis. The present work is an extension of these studies. Methods Thirty male rats were divided into 3 groups. All groups were given the same food, but various beverages: water (W), ammonium chloride, 200 mmol/L (AC), or sodium bicarbonate, 200 mmol/L (SB). Serum triglycerides, HDL cholesterol, and the fatty acid distribution in total serum lipids were determined. Delta9-desaturase in serum lipids was estimated by the ratio of palmitoleic to palmitic acid, and by the oleic/stearic acid ratio. Correlation and ANOVA were used to study associations and group differences. Results After 3 weeks, the AC group had higher triglyceride concentration and higher Delta9 desaturase indexes, but lower serum HDL and body weight as compared with the SB and W groups. In each of the groups, the oleic acid/stearic acid ratio correlated positively with serum triglycerides; in the pooled group the correlation coefficient was r = 0.963, p<0.01. Conclusions Rats ingesting ammonium chloride as compared with sodium bicarbonate responded with increased desaturase indexes, increased serum triglycerides, and lowered HDL cholesterol concentration, thereby possibly contributing to explain the increased triglyceride concentration previously observed in subjects with a frequent intake of acid beverages, such as sodas containing carbonic acid, citric acid, and phosphoric acid. PMID:23800210

Association of ADRB2 polymorphism with triglyceride levels in Tongans

PubMed Central

2013-01-01

Background Our previous study demonstrated that the A-allele of the single nucleotide polymorphism (SNP) rs34623097 located in the upstream region of the β2 adrenergic receptor gene (ADRB2) is significantly associated with risk for obesity in Oceanic populations. Methods To investigate whether the ADRB2 polymorphisms explain part of the individual differences in lipid mobilization, energy expenditure and glycogen breakdown, the associations of 10 ADRB2 SNPs with total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglyceride levels were examined in 128 adults in Tonga. Results A multiple linear regression analysis adjusted for age, sex, and body mass index revealed that rs34623097 was significantly associated with triglyceride levels (P-value = 0.037). A copy of the rs34623097-A allele increased serum triglyceride levels by 70.1 mg/dL (0.791 mmol/L). None of the ADRB2 SNPs showed a significant association with total-cholesterol, high-density lipoprotein cholesterol, or low-density lipoprotein cholesterol. Conclusions In a Tongan population, a SNP located in the upstream region of ADRB2 is associated with triglyceride levels independent of body mass index. PMID:23875540

The Central Clock Neurons Regulate Lipid Storage in Drosophila

PubMed Central

DiAngelo, Justin R.; Erion, Renske; Crocker, Amanda; Sehgal, Amita

2011-01-01

A proper balance of lipid breakdown and synthesis is essential for achieving energy homeostasis as alterations in either of these processes can lead to pathological states such as obesity. The regulation of lipid metabolism is quite complex with multiple signals integrated to control overall triglyceride levels in metabolic tissues. Based upon studies demonstrating effects of the circadian clock on metabolism, we sought to determine if the central clock cells in the Drosophila brain contribute to lipid levels in the fat body, the main nutrient storage organ of the fly. Here, we show that altering the function of the Drosophila central clock neurons leads to an increase in fat body triglycerides. We also show that although triglyceride levels are not affected by age, they are increased by expression of the amyloid-beta protein in central clock neurons. The effect on lipid storage seems to be independent of circadian clock output as changes in triglycerides are not always observed in genetic manipulations that result in altered locomotor rhythms. These data demonstrate that the activity of the central clock neurons is necessary for proper lipid storage. PMID:21625640

Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.

PubMed

Graham, Mark J; Lee, Richard G; Bell, Thomas A; Fu, Wuxia; Mullick, Adam E; Alexander, Veronica J; Singleton, Walter; Viney, Nick; Geary, Richard; Su, John; Baker, Brenda F; Burkey, Jennifer; Crooke, Stanley T; Crooke, Rosanne M

2013-05-24

Elevated plasma triglyceride levels have been recognized as a risk factor for the development of coronary heart disease. Apolipoprotein C-III (apoC-III) represents both an independent risk factor and a key regulatory factor of plasma triglyceride concentrations. Furthermore, elevated apoC-III levels have been associated with metabolic syndrome and type 2 diabetes mellitus. To date, no selective apoC-III therapeutic agent has been evaluated in the clinic. To test the hypothesis that selective inhibition of apoC-III with antisense drugs in preclinical models and in healthy volunteers would reduce plasma apoC-III and triglyceride levels. Rodent- and human-specific second-generation antisense oligonucleotides were identified and evaluated in preclinical models, including rats, mice, human apoC-III transgenic mice, and nonhuman primates. We demonstrated the selective reduction of both apoC-III and triglyceride in all preclinical pharmacological evaluations. We also showed that inhibition of apoC-III was well tolerated and not associated with increased liver triglyceride deposition or hepatotoxicity. A double-blind, placebo-controlled, phase I clinical study was performed in healthy subjects. Administration of the human apoC-III antisense drug resulted in dose-dependent reductions in plasma apoC-III, concomitant lowering of triglyceride levels, and produced no clinically meaningful signals in the safety evaluations. Antisense inhibition of apoC-III in preclinical models and in a phase I clinical trial with healthy subjects produced potent, selective reductions in plasma apoC-III and triglyceride, 2 known risk factors for cardiovascular disease. This compelling pharmacological profile supports further clinical investigations in hypertriglyceridemic subjects.

Baseline triglyceride levels and insulin sensitivity are major determinants of the increase of LDL particle size and buoyancy induced by rosuvastatin treatment in patients with primary hyperlipidemia.

PubMed

Kostapanos, Michael S; Milionis, Haralampos J; Lagos, Konstantinos G; Rizos, Christos B; Tselepis, Alexandros D; Elisaf, Moses S

2008-08-20

The influence of various statins on low-density-lipoprotein (LDL)-particle phenotype has been reportedly trivial or moderate. We assessed the effect of rosuvastatin (the newest statin available) on the LDL subfraction profile in patients with primary hyperlipidemia. One hundred and twenty patients with primary hyperlipidemia without evidence of cardiovascular disease were randomized to therapeutic lifestyle modification ('control' group, N=60) or therapeutic lifestyle modification plus rosuvastatin 20 mg/day (N=60). Laboratory evaluation was performed at baseline and 12 weeks post-treatment. LDL subfraction analysis was carried out electrophoretically using of high-resolution 3% polyacrylamide gel tubes and the Lipoprint LDL System. Rosuvastatin induced a redistribution of LDL-cholesterol from small-dense LDL particles to large-buoyant ones and increased the mean LDL particle size. This beneficial effect was observed only in patients with baseline triglyceride levels >or=150 mg/dl (mean LDL particle size 255+/-7 A vs 260+/-5 A, P<0.01), whereas the LDL subfraction profile was not altered in those with triglyceride levels <150 mg/dl. Stepwise multivariate linear regression analysis revealed that baseline triglyceride levels (R(2)=0.29, P=0.001) followed by baseline insulin resistance as assessed by the HOmeostasis Model Assessment (HOMA) (R(2)=0.25, P=0.001) were independently associated with the rosuvastatin-induced increase in the mean LDL particle size. In conclusion, rosuvastatin at 20 mg/day favorably modified the relative distribution of LDL-cholesterol distribution on LDL subfractions as well as on the mean LDL particle size in patients treated for primary dyslipidemia. Baseline triglyceride levels as well as baseline HOMA-index were found to be the major predictors of this beneficial action of rosuvastatin.

Common variants associated with plasma triglycerides and risk for coronary artery disease

PubMed Central

Do, Ron; Willer, Cristen J.; Schmidt, Ellen M.; Sengupta, Sebanti; Gao, Chi; Peloso, Gina M.; Gustafsson, Stefan; Kanoni, Stavroula; Ganna, Andrea; Chen, Jin; Buchkovich, Martin L.; Mora, Samia; Beckmann, Jacques S.; Bragg-Gresham, Jennifer L.; Chang, Hsing-Yi; Demirkan, Ayşe; Den Hertog, Heleen M.; Donnelly, Louise A.; Ehret, Georg B.; Esko, Tõnu; Feitosa, Mary F.; Ferreira, Teresa; Fischer, Krista; Fontanillas, Pierre; Fraser, Ross M.; Freitag, Daniel F.; Gurdasani, Deepti; Heikkilä, Kauko; Hyppönen, Elina; Isaacs, Aaron; Jackson, Anne U.; Johansson, Åsa; Johnson, Toby; Kaakinen, Marika; Kettunen, Johannes; Kleber, Marcus E.; Li, Xiaohui; Luan, Jian'an; Lyytikäinen, Leo-Pekka; Magnusson, Patrik K.E.; Mangino, Massimo; Mihailov, Evelin; Montasser, May E.; Müller-Nurasyid, Martina; Nolte, Ilja M.; O'Connell, Jeffrey R.; Palmer, Cameron D.; Perola, Markus; Petersen, Ann-Kristin; Sanna, Serena; Saxena, Richa; Service, Susan K.; Shah, Sonia; Shungin, Dmitry; Sidore, Carlo; Song, Ci; Strawbridge, Rona J.; Surakka, Ida; Tanaka, Toshiko; Teslovich, Tanya M.; Thorleifsson, Gudmar; Van den Herik, Evita G.; Voight, Benjamin F.; Volcik, Kelly A.; Waite, Lindsay L.; Wong, Andrew; Wu, Ying; Zhang, Weihua; Absher, Devin; Asiki, Gershim; Barroso, Inês; Been, Latonya F.; Bolton, Jennifer L.; Bonnycastle, Lori L; Brambilla, Paolo; Burnett, Mary S.; Cesana, Giancarlo; Dimitriou, Maria; Doney, Alex S.F.; Döring, Angela; Elliott, Paul; Epstein, Stephen E.; Eyjolfsson, Gudmundur Ingi; Gigante, Bruna; Goodarzi, Mark O.; Grallert, Harald; Gravito, Martha L.; Groves, Christopher J.; Hallmans, Göran; Hartikainen, Anna-Liisa; Hayward, Caroline; Hernandez, Dena; Hicks, Andrew A.; Holm, Hilma; Hung, Yi-Jen; Illig, Thomas; Jones, Michelle R.; Kaleebu, Pontiano; Kastelein, John J.P.; Khaw, Kay-Tee; Kim, Eric; Klopp, Norman; Komulainen, Pirjo; Kumari, Meena; Langenberg, Claudia; Lehtimäki, Terho; Lin, Shih-Yi; Lindström, Jaana; Loos, Ruth J.F.; Mach, François; McArdle, Wendy L; Meisinger, Christa; Mitchell, Braxton D.; Müller, Gabrielle; Nagaraja, Ramaiah; Narisu, Narisu; Nieminen, Tuomo V.M.; Nsubuga, Rebecca N.; Olafsson, Isleifur; Ong, Ken K.; Palotie, Aarno; Papamarkou, Theodore; Pomilla, Cristina; Pouta, Anneli; Rader, Daniel J.; Reilly, Muredach P.; Ridker, Paul M.; Rivadeneira, Fernando; Rudan, Igor; Ruokonen, Aimo; Samani, Nilesh; Scharnagl, Hubert; Seeley, Janet; Silander, Kaisa; Stančáková, Alena; Stirrups, Kathleen; Swift, Amy J.; Tiret, Laurence; Uitterlinden, Andre G.; van Pelt, L. Joost; Vedantam, Sailaja; Wainwright, Nicholas; Wijmenga, Cisca; Wild, Sarah H.; Willemsen, Gonneke; Wilsgaard, Tom; Wilson, James F.; Young, Elizabeth H.; Zhao, Jing Hua; Adair, Linda S.; Arveiler, Dominique; Assimes, Themistocles L.; Bandinelli, Stefania; Bennett, Franklyn; Bochud, Murielle; Boehm, Bernhard O.; Boomsma, Dorret I.; Borecki, Ingrid B.; Bornstein, Stefan R.; Bovet, Pascal; Burnier, Michel; Campbell, Harry; Chakravarti, Aravinda; Chambers, John C.; Chen, Yii-Der Ida; Collins, Francis S.; Cooper, Richard S.; Danesh, John; Dedoussis, George; de Faire, Ulf; Feranil, Alan B.; Ferrières, Jean; Ferrucci, Luigi; Freimer, Nelson B.; Gieger, Christian; Groop, Leif C.; Gudnason, Vilmundur; Gyllensten, Ulf; Hamsten, Anders; Harris, Tamara B.; Hingorani, Aroon; Hirschhorn, Joel N.; Hofman, Albert; Hovingh, G. Kees; Hsiung, Chao Agnes; Humphries, Steve E.; Hunt, Steven C.; Hveem, Kristian; Iribarren, Carlos; Järvelin, Marjo-Riitta; Jula, Antti; Kähönen, Mika; Kaprio, Jaakko; Kesäniemi, Antero; Kivimaki, Mika; Kooner, Jaspal S.; Koudstaal, Peter J.; Krauss, Ronald M.; Kuh, Diana; Kuusisto, Johanna; Kyvik, Kirsten O.; Laakso, Markku; Lakka, Timo A.; Lind, Lars; Lindgren, Cecilia M.; Martin, Nicholas G.; März, Winfried; McCarthy, Mark I.; McKenzie, Colin A.; Meneton, Pierre; Metspalu, Andres; Moilanen, Leena; Morris, Andrew D.; Munroe, Patricia B.; Njølstad, Inger; Pedersen, Nancy L.; Power, Chris; Pramstaller, Peter P.; Price, Jackie F.; Psaty, Bruce M.; Quertermous, Thomas; Rauramaa, Rainer; Saleheen, Danish; Salomaa, Veikko; Sanghera, Dharambir K.; Saramies, Jouko; Schwarz, Peter E.H.; Sheu, Wayne H-H; Shuldiner, Alan R.; Siegbahn, Agneta; Spector, Tim D.; Stefansson, Kari; Strachan, David P.; Tayo, Bamidele O.; Tremoli, Elena; Tuomilehto, Jaakko; Uusitupa, Matti; van Duijn, Cornelia M.; Vollenweider, Peter; Wallentin, Lars; Wareham, Nicholas J.; Whitfield, John B.; Wolffenbuttel, Bruce H.R.; Altshuler, David; Ordovas, Jose M.; Boerwinkle, Eric; Palmer, Colin N.A.; Thorsteinsdottir, Unnur; Chasman, Daniel I.; Rotter, Jerome I.; Franks, Paul W.; Ripatti, Samuli; Cupples, L. Adrienne; Sandhu, Manjinder S.; Rich, Stephen S.; Boehnke, Michael; Deloukas, Panos; Mohlke, Karen L.; Ingelsson, Erik; Abecasis, Goncalo R.; Daly, Mark J.; Neale, Benjamin M.; Kathiresan, Sekar

2013-01-01

Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P<5×10−8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD. PMID:24097064

rs11613352 polymorphism (TT genotype) associates with a decrease of triglycerides and an increase of HDL in familial hypercholesterolemia patients.

PubMed

Aledo, Rosa; Padró, Teresa; Mata, Pedro; Alonso, Rodrigo; Badimon, Lina

2015-04-01

Recent genome-wide association studies have identified a locus on chromosome 12q13.3 associated with plasma levels of triglyceride and high-density lipoprotein cholesterol, with rs11613352 being the lead single nucleotide polymorphism in this genome-wide association study locus. The aim of the study is to investigate the involvement of rs11613352 in a population with high cardiovascular risk due to familial hypercholesterolemia. The single nucleotide polymorphism was genotyped by Taqman(®) assay in a cohort of 601 unrelated familial hypercholesterolemia patients and its association with plasma triglyceride and high-density lipoprotein cholesterol levels was analyzed by multivariate methods based on linear regression. Minimal allele frequency was 0.17 and genotype frequencies were 0.69, 0.27, and 0.04 for CC, CT, and TT genotypes, respectively. The polymorphism is associated in a recessive manner (TT genotype) with a decrease in triglyceride levels (P=.002) and with an increase in high-density lipoprotein cholesterol levels (P=.021) after adjusting by age and sex. The polymorphism rs11613352 may contribute to modulate the cardiovascular risk by modifying plasma lipid levels in familial hypercholesterolemia patients. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The effects of fasting in Ramadan. 1. Serum uric acid and lipid concentrations.

PubMed

Gumaa, K A; Mustafa, K Y; Mahmoud, N A; Gader, A M

1978-11-01

1. The changes in serum levels of uric acid and lipids during 1 month of starvation-refeeding were measured in sixteen male volunteers. 2. Uric acid levels increased linearly with the duration of the experiment. The increase was positively correlated with the increase in serum triglycerides but not with cholesterol or phospholipids. 3. Triglycerides increased at a faster rate than uric acid implying that the increase in uric acid was secondary to that of the lipid. 4. It was concluded that the purine and lipid synthetic pathways are linked through a common small-molecular-weight effector rather than through the sharing of a common enzyme.

The effect of ghee (clarified butter) on serum lipid levels and microsomal lipid peroxidation.

PubMed

Sharma, Hari; Zhang, Xiaoying; Dwivedi, Chandradhar

2010-04-01

Ghee, also known as clarified butter, has been utilized for thousands of years in Ayurveda as a therapeutic agent. In ancient India, ghee was the preferred cooking oil. In the last several decades, ghee has been implicated in the increased prevalence of coronary artery disease (CAD) in Asian Indians due to its content of saturated fatty acids and cholesterol and, in heated ghee, cholesterol oxidation products. Our previous research on Sprague-Dawley outbred rats, which serve as a model for the general population, showed no effect of 5 and 10% ghee-supplemented diets on serum cholesterol and triglycerides. However, in Fischer inbred rats, which serve as a model for genetic predisposition to diseases, results of our previous research showed an increase in serum total cholesterol and triglyceride levels when fed a 10% ghee-supplemented diet. In the present study, we investigated the effect of 10% dietary ghee on microsomal lipid peroxidation, as well as serum lipid levels in Fischer inbred rats to assess the effect of ghee on free radical mediated processes that are implicated in many chronic diseases including cardiovascular disease. Results showed that 10% dietary ghee fed for 4 weeks did not have any significant effect on levels of serum total cholesterol, but did increase triglyceride levels in Fischer inbred rats. Ghee at a level of 10% in the diet did not increase liver microsomal lipid peroxidation or liver microsomal lipid peroxide levels. Animal studies have demonstrated many beneficial effects of ghee, including dose-dependent decreases in serum total cholesterol, low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides; decreased liver total cholesterol, triglycerides, and cholesterol esters; and a lower level of nonenzymatic-induced lipid peroxidation in liver homogenate. Similar results were seen with heated (oxidized) ghee which contains cholesterol oxidation products. A preliminary clinical study showed that high doses of medicated ghee decreased serum cholesterol, triglycerides, phospholipids, and cholesterol esters in psoriasis patients. A study on a rural population in India revealed a significantly lower prevalence of coronary heart disease in men who consumed higher amounts of ghee. Research on Maharishi Amrit Kalash-4 (MAK-4), an Ayurvedic herbal mixture containing ghee, showed no effect on levels of serum cholesterol, high density lipoprotein (HDL), LDL, or triglycerides in hyperlipidemic patients who ingested MAK-4 for 18 weeks. MAK-4 inhibited the oxidation of LDL in these patients. The data available in the literature do not support a conclusion of harmful effects of the moderate consumption of ghee in the general population. Factors that may be involved in the rise of CAD in Asian Indians include the increased use of vanaspati (vegetable ghee) which contains 40% trans fatty acids, psychosocial stress, insulin resistance, and altered dietary patterns. Research findings in the literature support the beneficial effects of ghee outlined in the ancient Ayurvedic texts and the therapeutic use of ghee for thousands of years in the Ayurvedic system of medicine.

Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial.

PubMed

Na, Lixin; Zhang, Qiao; Jiang, Shuo; Du, Shanshan; Zhang, Wei; Li, Ying; Sun, Changhao; Niu, Yucun

2015-05-19

Our previous studies have shown that mangiferin decreased serum triglycerides and free fatty acids (FFAs) by increasing FFAs oxidation in both animal and cell experiments. This study sought to evaluate the effects of mangiferin on serum lipid profiles in overweight patients with hyperlipidemia. Overweight patients with hyperlipidemia (serum triglyceride ≥ 1.70 mmol/L, and total cholesterol ≥ 5.2 mmol/L) were included in this double-blind randomized controlled trial. Participants were randomly allocated to groups, either receiving mangiferin (150 mg/day) or identical placebo for 12 weeks. The lipid profile and serum levels of mangiferin, glucose, L-carnitine, β-hydroxybutyrate, and acetoacetate were determined at baseline and 12 weeks. A total of 97 participants completed the trial. Compared with the placebo control, mangiferin supplementation significantly decreased the serum levels of triglycerides and FFAs, and insulin resistance index. Mangiferin supplementation also significantly increased the serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine, β-hydroxybutyrate, and acetoacetate, and increased lipoprotein lipase activity. However, there were no differences in the serum levels of total cholesterol, low-density lipoprotein cholesterol, serum glucose, and insulin between groups. Mangiferin supplementation could improve serum lipid profiles by reducing serum triglycerides and FFAs in overweight patients with hyperlipidemia, partly due to the promotion of FFAs oxidation.

Mangiferin supplementation improves serum lipid profiles in overweight patients with hyperlipidemia: a double-blind randomized controlled trial

PubMed Central

Na, Lixin; Zhang, Qiao; Jiang, Shuo; Du, Shanshan; Zhang, Wei; Li, Ying; Sun, Changhao; Niu, Yucun

2015-01-01

Our previous studies have shown that mangiferin decreased serum triglycerides and free fatty acids (FFAs) by increasing FFAs oxidation in both animal and cell experiments. This study sought to evaluate the effects of mangiferin on serum lipid profiles in overweight patients with hyperlipidemia. Overweight patients with hyperlipidemia (serum triglyceride ≥ 1.70 mmol/L, and total cholesterol ≥ 5.2 mmol/L) were included in this double-blind randomized controlled trial. Participants were randomly allocated to groups, either receiving mangiferin (150 mg/day) or identical placebo for 12 weeks. The lipid profile and serum levels of mangiferin, glucose, L-carnitine, β-hydroxybutyrate, and acetoacetate were determined at baseline and 12 weeks. A total of 97 participants completed the trial. Compared with the placebo control, mangiferin supplementation significantly decreased the serum levels of triglycerides and FFAs, and insulin resistance index. Mangiferin supplementation also significantly increased the serum levels of mangiferin, high-density lipoprotein cholesterol, L-carnitine, β-hydroxybutyrate, and acetoacetate, and increased lipoprotein lipase activity. However, there were no differences in the serum levels of total cholesterol, low-density lipoprotein cholesterol, serum glucose, and insulin between groups. Mangiferin supplementation could improve serum lipid profiles by reducing serum triglycerides and FFAs in overweight patients with hyperlipidemia, partly due to the promotion of FFAs oxidation. PMID:25989216

Correlation between Glycated Hemoglobin and Triglyceride Level in Type 2 Diabetes Mellitus.

PubMed

Naqvi, Syeda; Naveed, Shabnam; Ali, Zeeshan; Ahmad, Syed Masroor; Asadullah Khan, Raad; Raj, Honey; Shariff, Shoaib; Rupareliya, Chintan; Zahra, Fatima; Khan, Saba

2017-06-13

Dyslipidemia is quite prevalent in non-insulin dependent diabetes mellitus. Maintaining tight glycemic along with lipid control plays an essential role in preventing micro- and macro-vascular complications associated with diabetes. The main purpose of the study was to highlight the relationship between glycosylated hemoglobin (HbA1c) and triglyceride levels. This may in turn help in predicting the triglyceride status of type 2 diabetics and therefore identifying patients at increased risk from cardiovascular events. Hypertriglyceridemia is one of the common risk factors for coronary artery disease in type 2 diabetes mellitus (DM). Careful monitoring of the blood glucose level can be used to predict lipid status and can prevent most of the complications associated with the disease. This is a cross-sectional study using data collected from the outpatient diabetic clinic of Jinnah Postgraduate Medical Centre (JPMC) Karachi, Pakistan. Patients of age 18 years and above were recruited from the clinic. A total of consenting 509 patients of type 2 diabetes mellitus were enrolled over a period of 11 months.  For statistical analysis, SPSS Statistics for Windows, Version 17.0 ( IBM Corp, Armonk, New York) was used and Chi-square and Pearson's correlation coefficient was used to find the association between triglyceride and HbA1c. The HbA1c was dichotomized into four groups on the basis of cut-off. Chi-square was used for association between HbA1c with various cut-off values and high triglyceride levels. Odds-ratio and its 95% confidence interval were calculated to estimate the level of risk between high triglyceride levels and HbA1c groups. The p-value < 0.05 was considered statistically significant for all the tests applied for significance. The association of high triglyceride was evaluated in four different groups of HbA1c, with a cut-off seven, eight, nine and 10 respectively. With HbA1c cut-off value of 7%, 74% patients had high triglycerides and showed a significant association with high triglyceride levels at p < 0.001 and odds ratio was 2.038 (95% confidence interval: 1.397 - 2.972). Logistic regression models were adjusted for demographic factors (age, race, gender), lifestyle factors (smoking, body mass index, lifestyle) and health status factors (blood pressure, physician-rated health status). After adjusting for relevant covariates, glycated hemoglobin was positively correlated with high triglyceride. Hence, HbA1c can be an indicator of triglyceride level and can be one of the predictors of cardiovascular risk factors in type 2 diabetes mellitus.

Clinical symptoms in fibromyalgia are associated to overweight and lipid profile.

PubMed

Cordero, Mario D; Alcocer-Gómez, Elísabet; Cano-García, Francisco J; Sánchez-Domínguez, Benito; Fernández-Riejo, Patricia; Moreno Fernández, Ana M; Fernández-Rodríguez, Ana; De Miguel, Manuel

2014-03-01

In order to analyze the association between body mass index (BMI), lipid profile and clinical symptoms in patients with fibromyalgia, we assessed BMI levels, lipid profile and its association with clinical symptoms in 183 patients with fibromyalgia. The patients were evaluated using tender points, FIQ and Visual Analogue Scales of pain (VAS). Serum lipid profile analysis (total cholesterol, triglyceride, HDL, LDL and VLDL), and biochemical parameters were measured in the biochemistry laboratory. The BMI distribution of the nonobese, overweight and obese patients' groups were relatively even with 37.7, 35.5 and 26.8%, respectively, with a mean BMI of 27.3 ± 4.9. The number of tender points showed significantly positive correlation with higher BMI (P < 0.05). A total of 57.9% of patients showed increased levels of total cholesterol, 63.4 % increased levels of LDL cholesterol and 19.9% high levels of triglycerides. BMI, total cholesterol and triglycerides showed high association with some clinical parameters. Overweight and lipid profile could be associated with fibromyalgia symptoms. A treatment program with weight loss strategies, and control in diet and increased physical activity is advised to patients.

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.

Antilithiasic and Hypolipidaemic Effects of Raphanus sativus L. var. niger on Mice Fed with a Lithogenic Diet

PubMed Central

Castro-Torres, Ibrahim Guillermo; Naranjo-Rodríguez, Elia Brosla; Domínguez-Ortíz, Miguel Ángel; Gallegos-Estudillo, Janeth; Saavedra-Vélez, Margarita Virginia

2012-01-01

In Mexico, Raphanus sativus L. var. niger (black radish) has uses for the treatment of gallstones and for decreasing lipids serum levels. We evaluate the effect of juice squeezed from black radish root in cholesterol gallstones and serum lipids of mice. The toxicity of juice was analyzed according to the OECD guidelines. We used female C57BL/6 mice fed with a lithogenic diet. We performed histopathological studies of gallbladder and liver, and measured concentrations of cholesterol, HDL cholesterol and triglycerides. The juice can be considered bioactive and non-toxic; the lithogenic diet significantly induced cholesterol gallstones; increased cholesterol and triglycerides levels, and decreased HDL levels; gallbladder wall thickness increased markedly, showing epithelial hyperplasia and increased liver weight. After treatment with juice for 6 days, cholesterol gallstones were eradicated significantly in the gallbladder of mice; cholesterol and triglycerides levels decreased too, and there was also an increase in levels of HDL (P < 0.05). Gallbladder tissue continued to show epithelial hyperplasia and granulocyte infiltration; liver tissue showed vacuolar degeneration. The juice of black radish root has properties for treatment of cholesterol gallstones and for decreasing serum lipids levels; therefore, we confirm in a preclinical study the utility that people give it in traditional medicine. PMID:23093836

Effect of adiponectin-encoding gene ADIPOQ single nucleotide polymorphisms +45 and +276 on serum lipid levels after antiretroviral therapy in Japanese patients with HIV-1-infection.

PubMed

Kato, Hideaki; Ohata, Aya; Samukawa, Sei; Ueda, Atsuhisa; Ishigatsubo, Yoshiaki

2016-04-01

To investigate the association between single nucleotide polymorphisms (SNPs) in the adiponectin-encoding gene ADIPOQ and changes in serum lipid levels in HIV-1-infected patients after antiretroviral therapy (ART). ART-naïve HIV-1-infected patients were recruited to this prospective analysis. SNP +45 and SNP +276 genotype was determined by direct sequencing. Multivariate linear regression analysis was performed to analyse the effects of genotype, and predisposing conditions on serum total cholesterol and triglyceride in the 4 months before and after ART initiation. The study enrolled 78 patients with HIV-1-infection (73 male, five female; age range 22-67 years). HIV-1 viral load ≥5 log10 copies/ml, baseline total cholesterol ≥160 mg/dl, and CD4(+) lymphocyte count <200/µl were associated with increased serum total cholesterol levels after ART initiation. Protease inhibitor treatment and body mass index ≥25 kg/m(2) were associated with increased triglyceride levels after ART initiation. There were no significant associations between SNP +45 or SNP +276 genotype and serum total cholesterol or triglyceride levels. SNP +45 and SNP +276 genotype is not associated with changes in serum total cholesterol or triglyceride levels after ART initiation. © The Author(s) 2016.

Factors influencing insulin resistance in relation to atherogenicity in mood disorders, the metabolic syndrome and tobacco use disorder.

PubMed

Bortolasci, Chiara Cristina; Vargas, Heber Odebrecht; Vargas Nunes, Sandra Odebrecht; de Melo, Luiz Gustavo Piccoli; de Castro, Márcia Regina Pizzo; Moreira, Estefania Gastaldello; Dodd, Seetal; Barbosa, Décio Sabbatini; Berk, Michael; Maes, Michael

2015-07-01

This study examines the effects of malondialdehyde (MDA) and uric acid on insulin resistance and atherogenicity in subjects with and without mood disorders, the metabolic syndrome (MetS) and tobacco use disorder (TUD). We included 314 subjects with depression and bipolar depression, with and without the MetS and TUD and computed insulin resistance using the updated homeostasis model assessment (HOMA2IR) and atherogenicity using the atherogenic index of plasma (AIP), that is log10 (triglycerides/high density lipoprotein (HDL) cholesterol. HOMA2IR is correlated with body mass index (BMI) and uric acid levels, but not with mood disorders and TUD, while the AIP is positively associated with BMI, mood disorders, TUD, uric acid, MDA and male sex. Uric acid is positively associated with insulin and triglycerides and negatively with HDL cholesterol. MDA is positively associated with triglyceride levels. Comorbid mood disorders and TUD further increase AIP but not insulin resistance. Glucose is positively associated with increasing age, male gender and BMI. The results show that mood disorders, TUD and BMI together with elevated levels of uric acid and MDA independently contribute to increased atherogenic potential, while BMI and uric acid are risk factors for insulin resistance. The findings show that mood disorders and TUD are closely related to an increased atherogenic potential but not to insulin resistance or the MetS. Increased uric acid is a highly significant risk factor for insulin resistance and increased atherogenic potential. MDA, a marker of lipid peroxidation, further contributes to different aspects of the atherogenic potential. Mood disorders and TUD increase triglyceride levels, lower HDL cholesterol and are strongly associated with the atherogenic, but not insulin resistance, component of the MetS. Copyright © 2015 Elsevier B.V. All rights reserved.

Magnolol-mediated regulation of plasma triglyceride through affecting lipoprotein lipase activity in apolipoprotein A5 knock-in mice.

PubMed

Chang, Chun-Kai; Lin, Xiu-Ru; Lin, Yen-Lin; Fang, Woei-Horng; Lin, Shu-Wha; Chang, Sui-Yuan; Kao, Jau-Tsuen

2018-01-01

Hyperlipidemia is a risk factor of arteriosclerosis, stroke, and other coronary heart disease, which has been shown to correlate with single nucleotide polymorphisms of genes essential for lipid metabolism, such as lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5). In this study, the effect of magnolol, the main active component extracted from Magnolia officinalis, on LPL activity was investigated. A dose-dependent up-regulation of LPL activity, possibly through increasing LPL mRNA transcription, was observed in mouse 3T3-L1 pre-adipocytes cultured in the presence of magnolol for 6 days. Subsequently, a transgenic knock-in mice carrying APOA5 c.553G>T variant was established and then fed with corn oil with or without magnolol for four days. The baseline plasma triglyceride levels in transgenic knock-in mice were higher than those in wild-type mice, with the highest increase occurred in homozygous transgenic mice (106 mg/dL vs 51 mg/dL, p<0.01). After the induction of hyperglyceridemia along with the administration of magnolol, the plasma triglyceride level in heterozygous transgenic mice was significantly reduced by half. In summary, magnolol could effectively lower the plasma triglyceride levels in APOA5 c.553G>T variant carrier mice and facilitate the triglyceride metabolism in postprandial hypertriglyceridemia.

Magnolol-mediated regulation of plasma triglyceride through affecting lipoprotein lipase activity in apolipoprotein A5 knock-in mice

PubMed Central

Lin, Yen-Lin; Fang, Woei-Horng; Lin, Shu-Wha; Kao, Jau-Tsuen

2018-01-01

Hyperlipidemia is a risk factor of arteriosclerosis, stroke, and other coronary heart disease, which has been shown to correlate with single nucleotide polymorphisms of genes essential for lipid metabolism, such as lipoprotein lipase (LPL) and apolipoprotein A5 (APOA5). In this study, the effect of magnolol, the main active component extracted from Magnolia officinalis, on LPL activity was investigated. A dose-dependent up-regulation of LPL activity, possibly through increasing LPL mRNA transcription, was observed in mouse 3T3-L1 pre-adipocytes cultured in the presence of magnolol for 6 days. Subsequently, a transgenic knock-in mice carrying APOA5 c.553G>T variant was established and then fed with corn oil with or without magnolol for four days. The baseline plasma triglyceride levels in transgenic knock-in mice were higher than those in wild-type mice, with the highest increase occurred in homozygous transgenic mice (106 mg/dL vs 51 mg/dL, p<0.01). After the induction of hyperglyceridemia along with the administration of magnolol, the plasma triglyceride level in heterozygous transgenic mice was significantly reduced by half. In summary, magnolol could effectively lower the plasma triglyceride levels in APOA5 c.553G>T variant carrier mice and facilitate the triglyceride metabolism in postprandial hypertriglyceridemia. PMID:29425239

Postprandial Monocyte Activation in Individuals With Metabolic Syndrome

PubMed Central

Khan, Ilvira M.; Pokharel, Yashashwi; Dadu, Razvan T.; Lewis, Dorothy E.; Hoogeveen, Ron C.; Wu, Huaizhu

2016-01-01

Context: Postprandial hyperlipidemia has been suggested to contribute to atherogenesis by inducing proinflammatory changes in monocytes. Individuals with metabolic syndrome (MS), shown to have higher blood triglyceride concentration and delayed triglyceride clearance, may thus have increased risk for development of atherosclerosis. Objective: Our objective was to examine fasting levels and effects of a high-fat meal on phenotypes of monocyte subsets in individuals with obesity and MS and in healthy controls. Design, Setting, Participants, Intervention: Individuals with obesity and MS and gender- and age-matched healthy controls were recruited. Blood was collected from participants after an overnight fast (baseline) and at 3 and 5 hours after ingestion of a high-fat meal. At each time point, monocyte phenotypes were examined by multiparameter flow cytometry. Main Outcome Measures: Baseline levels of activation markers and postprandial inflammatory response in each of the three monocyte subsets were measured. Results: At baseline, individuals with obesity and MS had higher proportions of circulating lipid-laden foamy monocytes than controls, which were positively correlated with fasting triglyceride levels. Additionally, the MS group had increased counts of nonclassical monocytes, higher CD11c, CX3CR1, and human leukocyte antigen-DR levels on intermediate monocytes, and higher CCR5 and tumor necrosis factor-α levels on classical monocytes in the circulation. Postprandial triglyceride increases in both groups were paralleled by upregulation of lipid-laden foamy monocytes. MS, but not control, subjects had significant postprandial increases of CD11c and percentages of IL-1β+ and tumor necrosis factor-α+ cells in nonclassical monocytes. Conclusions: Compared to controls, individuals with obesity and MS had increased fasting and postprandial monocyte lipid accumulation and activation. PMID:27575945

ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial

PubMed Central

2011-01-01

Background Elevated triglyceride levels are a risk factor for cardiovascular disease. Angiopoietin-like protein 4 (Angptl4) is a metabolic factor that raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL). In non-diabetic individuals, the ANGPTL4 coding variant E40K has been associated with lower plasma triglyceride levels while the T266M variant has been associated with more modest effects on triglyceride metabolism. The objective of this study was to determine whether ANGPTL4 E40K and T266M are associated with triglyceride levels in the setting of obesity and T2D, and whether modification of triglyceride levels by these genetic variants is altered by a lifestyle intervention designed to treat T2D. Methods The association of ANGPTL4 E40K and T266M with fasting triglyceride levels was investigated in 2,601 participants from the Look AHEAD Clinical Trial, all of whom had T2D and were at least overweight. Further, we tested for an interaction between genotype and treatment effects on triglyceride levels. Results Among non-Hispanic White Look AHEAD participants, ANGPTL4 K40 carriers had mean triglyceride levels of 1.61 ± 0.62 mmol/L, 0.33 mmol/L lower than E40 homozygotes (p = 0.001). Individuals homozygous for the minor M266 allele (MAF 30%) had triglyceride levels of 1.75 ± 0.58 mmol/L, 0.24 mmol/L lower than T266 homozygotes (p = 0.002). The association of the M266 with triglycerides remained significant even after removing K40 carriers from the analysis (p = 0.002). There was no interaction between the weight loss intervention and genotype on triglyceride levels. Conclusions This is the first study to demonstrate that the ANGPTL4 E40K and T266M variants are associated with lower triglyceride levels in the setting of T2D. In addition, our findings demonstrate that ANGPTL4 genotype status does not alter triglyceride response to a lifestyle intervention in the Look AHEAD study. PMID:21714923

Association of faecal elastase 1 with non-fasting triglycerides in type 2 diabetes.

PubMed

Rathmann, Wolfgang; Haastert, Burkhard; Oscarsson, Jan; Berglind, Niklas; Lindkvist, Björn; Wareham, Nicholas J

2016-01-01

Intestinal absorption of esterified fatty acids depends on exocrine pancreatic function and influences plasma triglycerides levels. The aim was to investigate the association of reduced exocrine pancreatic function (low fecal elastase-1; FE1) with plasma triglycerides in type 2 diabetes and controls without diabetes. FE1 (μg/g stool) and non-fasting plasma triglyceride measurements were undertaken in 544 type 2 diabetes patients (age: 63 ± 8 years) randomly selected from diabetes registers in Cambridgeshire (UK), and 544 matched controls (age, sex, practice) without diabetes. Linear regression models were fitted using FE1 as dependent and log-triglycerides as independent variable adjusting for sex, age, body mass index, alcohol consumption, serum lipase, HbA1c, and smoking. FE1 concentrations were lower (mean ± SD: 337 ± 204 vs. 437 ± 216 μg/g, p < 0.05) and plasma triglycerides were higher (geometric mean */: standard deviation factor: 2.2*/:1.9 vs. 1.6*/:1.8 mmol/l, p < 0.05) in type 2 diabetes compared to controls, respectively. Within the category of type 2 diabetes and controls separately, a 10% increase in plasma triglycerides was associated with 4.5 μg/g higher FE1 concentrations (p < 0.01) after adjusting for confounders. In contrast, in diabetes patients and controls with pathological FE1 (<100 μg/g), low FE1 levels were associated with high plasma triglycerides (significant only in controls). Non-fasting triglycerides were positively related to FE1 in both type 2 diabetes and controls suggesting that impairment of exocrine pancreas function is influencing plasma triglycerides. Marked loss of exocrine pancreatic function had the opposite effect, resulting in higher levels of plasma triglycerides. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Apolipoprotein C-III in triglyceride-rich lipoprotein metabolism.

PubMed

Ramms, Bastian; Gordts, Philip L S M

2018-06-01

Apolipoprotein (apo) C-III is a key player in triglyceride-rich lipoprotein metabolism and strongly associated with elevated plasma triglyceride levels. Several new studies added important insights on apoC-III and its physiological function confirming its promise as a valid therapeutic target. APOC3 is expressed in liver and intestine and regulates triglyceride-rich lipoprotein (TRL) catabolism and anabolism. The transcriptional regulation in both organs requires different regulatory elements. Clinical and preclinical studies established that apoC-III raises plasma triglyceride levels predominantly by inhibiting hepatic TRL clearance. Mechanistic insights into missense variants indicate accelerated renal clearance of apoC-III variants resulting in enhanced TRL catabolism. In contrast, an APOC3 gain-of-function variant enhances de novo lipogenesis and hepatic TRL production. Multiple studies confirmed the correlation between increased apoC-III levels and cardiovascular disease. This has opened up new therapeutic avenues allowing targeting of specific apoC-III properties in triglyceride metabolism. Novel in vivo models and APOC3 missense variants revealed unique mechanisms by which apoC-III inhibits TRL catabolism. Clinical trials with Volanesorsen, an APOC3 antisense oligonucleotide, report very promising lipid-lowering outcomes. However, future studies will need to address if acute apoC-III lowering will have the same clinical benefits as a life-long reduction.

Lipid levels in dissociative disorders: effects of psychodynamic psychotherapy.

PubMed

Damsa, Cristian; Lazignac, Coralie; Miller, Nick; Maris, Susanne; Adam, Eric; Rossignon, Kevin

2014-09-01

Although there are several data suggesting a link between lower lipids levels and the risk of suicide, there are few data concerning lower lipids levels in patients with dissociative disorders (DD). This is the first longitudinal study investigating the evolution of the lipids levels during a specific 8 weeks of psychodynamic psychotherapy (PP) for patients with DD. 32 patients diagnosed with DD (SCID for DSMIVR) were assessed with Dissociative Experiences Scale (DES), Clinical Global Impression and Improvement Scale and their lipids levels (total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein and very low density lipoprotein) were measured at inclusion and after 3 and 8 weeks of PP. 30 patients finished the study. There is a significant positive (p < 0.05) link between lower lipids levels (total cholesterol, LDL, triglycerids) and a higher level of dissociation (DES scores) at the beginning and at the end of the study. Interestingly, we found a significant (p = 0.018) positive link between the reduction of the dissociation (DES) and the increase of the triglycerides levels after 8 weeks of treatment. While lower lipids seems related to a higher level of dissociation before and after the treatment, an increasing triglycerides level was observed after 8 weeks of PP in patients with a better outcome. Further studies are needed with larger samples and control groups, in order to confirm these preliminary data. These findings could open the way for hypothesis about the role of lipids in the pathophysiology of DD and raise the question of the patients with DD receiving antilipidemiants agents.

Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins.

PubMed

Schwartz, Gregory G; Abt, Markus; Bao, Weihang; DeMicco, David; Kallend, David; Miller, Michael; Mundl, Hardi; Olsson, Anders G

2015-06-02

Most patients with acute coronary syndrome (ACS) are treated with statins, which reduce atherogenic triglyceride-rich lipoproteins. It is uncertain whether triglycerides predict risk after ACS on a background of statin treatment. This study examined the relationship of fasting triglyceride levels to outcomes after ACS in patients treated with statins. Long-term and short-term relationships of triglycerides to risk after ACS were examined in the dal-OUTCOMES trial and atorvastatin arm of the MIRACL (Myocardial Ischemia Reduction with Acute Cholesterol Lowering) trial, respectively. Analysis of dal-OUTCOMES included 15,817 patients (97% statin-treated) randomly assigned 4 to 12 weeks after ACS to treatment with dalcetrapib (a cholesteryl ester transfer protein inhibitor) or placebo and followed for a median 31 months. Analysis of MIRACL included 1,501 patients treated with atorvastatin 80 mg daily beginning 1 to 4 days after ACS and followed for 16 weeks. Fasting triglycerides at initial random assignment were related to risk of coronary heart disease death, nonfatal myocardial infarction, stroke, and unstable angina in models adjusted for age, sex, hypertension, smoking, diabetes, high-density lipoprotein cholesterol, and body mass index. Fasting triglyceride levels were associated with both long-term and short-term risk after ACS. In dal-OUTCOMES, long-term risk increased across quintiles of baseline triglycerides (p<0.001). The hazard ratio in the highest/lowest quintile (>175/≤80 mg/dl) was 1.61 (95% confidence interval: 1.34 to 1.94). There was no interaction of triglycerides and treatment assignment on the primary outcome. In the atorvastatin group of MIRACL, short-term risk increased across tertiles of baseline triglycerides (p=0.03), with a hazard ratio of 1.50 [corrected] (95% confidence interval: 1.05 to 2.15) in highest/lowest tertiles (>195/≤135 mg/dl). The relationship of triglycerides to risk was independent of low-density lipoprotein cholesterol in both studies. Among patients with ACS treated effectively with statins, fasting triglycerides predict long-term and short-term cardiovascular risk. Triglyceride-rich lipoproteins may be an important additional target for therapy. (A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome; NCT00658515). Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Triglycerides are a predictive factor for arterial stiffness: a community-based 4.8-year prospective study.

PubMed

Wang, Xiaona; Ye, Ping; Cao, Ruihua; Yang, Xu; Xiao, Wenkai; Zhang, Yun; Bai, Yongyi; Wu, Hongmei

2016-05-18

Epidemiological studies have disclosed an independent effect of triglycerides on coronary heart disease despite achievement of low-density lipoprotein cholesterol goals with statin therapy. Arterial stiffness has been increasingly recognized as a strong predictor of cardiovascular disease and atherosclerotic disease. The association between triglycerides and arterial stiffness is not well characterized. We aimed to determine the relationship between triglycerides and arterial stiffness in a community-based longitudinal sample from Beijing, China. We related levels of plasma TGs to measures of arterial stiffness (carotid-femoral pulse wave velocity [PWV] and carotid-radial PWV) in 1447 subjects (mean age, 61.3 years) from a community-based population in Beijing, China. After a median follow-up interval of 4.8 years, multiple linear regression analysis revealed that TGs were independently associated with carotid-femoral PWV (β = 0.747, P < 0.001) and carotid-radial PWV (β = 0.367, P = 0.001). In the group older than 65 years, the association between baseline TG levels and follow-up carotid-femoral PWV (β = 1.094, P = 0.001) and carotid-radial PWV (β = 0.524, P = 0.002) were strengthened. In forward stepwise multivariate logistic regression analysis, every SD increase in TGδ was associated with a 1.296-increased likelihood of the presence of carotid-femoral PWVδII (OR [per SD increase in TGδ]: 1.296; 95% CI: 1.064 ~ 1.580; P = 0.010) in Model 2, whereas the relationship between TGδ and carotid-radial PWVδII disappeared. In addition, the relationship was strengthened between TGδ and the presence of carotid-femoral PWVδII (OR 1.526, 95% CI: 1.088-2.141, P = 0.014) in the group older than 65 years but not carotid-radial PWVδII. No association was noted in subjects younger than 65 years. Lower triglyceride levels were significantly associated with decreases in carotid-femoral PWV, indicating that achieving low TG levels may be an additional therapeutic consideration in subjects with atherosclerotic disease.

Plasma thyroid hormone concentration is associated with hepatic triglyceride content in patients with type 2 diabetes.

PubMed

Bril, Fernando; Kadiyala, Sushma; Portillo Sanchez, Paola; Sunny, Nishanth E; Biernacki, Diane; Maximos, Maryann; Kalavalapalli, Srilaxmi; Lomonaco, Romina; Suman, Amitabh; Cusi, Kenneth

2016-01-01

The underlying mechanisms responsible for the development and progression of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) are unclear. Since the thyroid hormone regulates mitochondrial function in the liver, we designed this study in order to establish the association between plasma free T4 levels and hepatic triglyceride accumulation and histological severity of liver disease in patients with T2DM and NAFLD. This is a cross-sectional study including a total of 232 patients with T2DM. All patients underwent a liver MR spectroscopy ((1)H-MRS) to quantify hepatic triglyceride content, and an oral glucose tolerance test to estimate insulin resistance. A liver biopsy was performed in patients with a diagnosis of NAFLD. Patients were divided into 5 groups according to plasma free T4 quintiles. We observed that decreasing free T4 levels were associated with an increasing prevalence of NAFLD (from 55% if free T4≥1.18 ng/dL to 80% if free T4<0.80 ng/dL, p=0.016), and higher hepatic triglyceride accumulation by (1)H-MRS (p<0.001). However, lower plasma free T4 levels were not significantly associated with more insulin resistance or more severe liver histology (ie, inflammation, ballooning, or fibrosis). Decreasing levels of plasma free T4 are associated with a higher prevalence of NAFLD and increasing levels of hepatic triglyceride content in patients with T2DM. These results suggest that thyroid hormone may play a role in the regulation of hepatic steatosis and support the notion that hypothyroidism may be associated with NAFLD. No NCT number required. Copyright © 2016 American Federation for Medical Research.

Angptl4 does not control hyperglucagonemia or α-cell hyperplasia following glucagon receptor inhibition

PubMed Central

Okamoto, Haruka; Cavino, Katie; Na, Erqian; Krumm, Elizabeth; Kim, Steven; Stevis, Panayiotis E.; Harp, Joyce; Murphy, Andrew J.; Yancopoulos, George D.; Gromada, Jesper

2017-01-01

Genetic disruption or pharmacologic inhibition of glucagon signaling effectively lowers blood glucose but results in compensatory glucagon hypersecretion involving expansion of pancreatic α-cell mass. Ben-Zvi et al. recently reported that angiopoietin-like protein 4 (Angptl4) links glucagon receptor inhibition to hyperglucagonemia and α-cell proliferation [Ben-Zvi et al. (2015) Proc Natl Acad Sci USA 112:15498–15503]. Angptl4 is a secreted protein and inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance. We report that Angptl4−/− mice treated with an anti-glucagon receptor monoclonal antibody undergo elevation of plasma glucagon levels and α-cell expansion similar to wild-type mice. Overexpression of Angptl4 in liver of mice caused a 8.6-fold elevation in plasma triglyceride levels, but did not alter plasma glucagon levels or α-cell mass. Furthermore, administration of glucagon receptor-blocking antibody to healthy individuals increased plasma glucagon and amino acid levels, but did not change circulating Angptl4 concentration. These data show that Angptl4 does not link glucagon receptor inhibition to compensatory hyperglucagonemia or expansion of α-cell mass, and that it cannot be given to induce such secretion and growth. The reduction of plasma triglyceride levels in Angptl4−/− mice and increase following Angptl4 overexpression suggest that changes in plasma triglyceride metabolism do not regulate α-cells in the pancreas. Our findings corroborate recent data showing that increased plasma amino acids and their transport into α-cells link glucagon receptor blockage to α-cell hyperplasia. PMID:28143927

Triglyceride response to an intensive lifestyle intervention is enhanced in carriers of the GCKR Pro446Leu polymorphism.

PubMed

Pollin, Toni I; Jablonski, Kathleen A; McAteer, Jarred B; Saxena, Richa; Kathiresan, Sekar; Kahn, Steven E; Goldberg, Ronald B; Altshuler, David; Florez, Jose C

2011-07-01

Glucokinase regulatory protein (GCKR) regulates the trafficking and enzymatic activity of hepatic glucokinase, the rate-limiting enzyme in glycogen synthesis and glycolysis. The intronic single-nucleotide polymorphism (SNP) rs780094 (intron 16) and the missense SNP rs1260326 (P446L) in the GCKR gene are strongly associated with increased circulating triglyceride and C-reactive protein levels and, paradoxically, reductions in diabetes incidence, fasting glucose levels, and insulin resistance. OBJECTIVE, SETTING, AND PATIENTS: We sought to replicate these associations and evaluate interactions with lifestyle and metformin interventions in the multiethnic Diabetes Prevention Program (DPP). We genotyped the two GCKR SNP in 3346 DPP participants and evaluated association with progression to diabetes and both baseline levels and changes in triglycerides, homeostasis model assessment of insulin resistance (HOMA-IR), oral disposition index, and inflammatory markers along with their interactions with DPP interventions. GCKR variation did not predict development of type 2 diabetes. At baseline, the 446L allele was associated with higher triglyceride and C-reactive protein levels (both P < 0.0001) and lower fasting glucose (P = 0.001) and HOMA-IR (P = 0.06). The lifestyle intervention was associated with a decrease in magnitude of the effect of the 446L allele on triglyceride levels (interaction P = 0.04). Metformin was more effective in reducing HOMA-IR in carriers of the P446 allele (interaction P = 0.05). Intensive lifestyle intervention appears to partially mitigate the effect of the 446L allele on higher triglycerides, whereas the P446 allele appears to enhance responsiveness to the HOMA-IR-lowering effect of metformin.

Pleiotropic effects of fenofibrate therapy on rats with hypertriglycemia.

PubMed

Sun, Bing; Xie, Yuan; Jiang, Jinfa; Wang, Yiping; Xu, Xiaolin; Zhao, Cuimei; Huang, Feifei

2015-04-14

Cardio-protective effect of fibrate therapy is controversial and current research is to evaluate the effect of fenofibrate therapy on rats with hypertriglycemia. Rats with hypertriglycemia were produced by 10% fructose administration (10 ml daily) for 4 weeks. After model has been successfully produced as reflected by increased triglyceride level, different doses of fenofibrate, namely low dose (50 mg/kg body weight) and high dose (100 mg/kg body weight), were orally prescribed for 2 weeks. At baseline, 4 weeks of fructose administration and 2 weeks of fenofibrate therapy, parameters of interest were evaluated and compared. At baseline, no significant differences of parameter were observed between groups. After 4 weeks of fructose prescription, triglyceride level increased in company with high density lipoprotein cholesterol (HDL-C) and apoprotein A1 (ApoA1) decreased. C-reactive protein (CRP) and malondialdehyde (MDA) levels were also elevated. Endothelial function was impaired as reflected by reduced nitric oxide (NO) production and elevated serum asymmetric dimethylarginine (ADMA) level. All these changes were significant as compared to the control group (P<0.05), suggesting that short-term of triglyceride elevation could potently initiate atherosclerosis. With 2 weeks of fenofibrate therapy, in comparison to un-treated group, triglyceride level was significantly reduced in parallel with HDL-C and ApoA1 elevation. Inflammation and oxidation were also profoundly ameliorated as reflected by CRP and MDA reduction. Notably, NO production was enhanced in company with serum ADMA level decrease. Overall, these improvements manifested in a dose-dependent manner, which was supported by multivariate regression analysis showing that after adjusted to other variables, the dose of fenofibrate therapy remained significantly associated with NO production and serum ADMA level, with OR of 1.042 (high-dose versus low-dose, 95% CI 1.028-1.055, P<0.05). Fenofibrate therapy not only could reduce triglyceride level but also confer pleiotropic effects in terms of endothelium-protection and amelioration of inflammation and oxidation in a dose-dependent manner.

Regulation of liver glucokinase activity in rats with fructose-induced insulin resistance and impaired glucose and lipid metabolism.

PubMed

Francini, Flavio; Castro, María C; Gagliardino, Juan J; Massa, María L

2009-09-01

We evaluated the relative role of different regulatory mechanisms, particularly 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFK2/FBPase-2), in liver glucokinase (GK) activity in intact animals with fructose-induced insulin resistance and impaired glucose and lipid metabolism. We measured blood glucose, triglyceride and insulin concentration, glucose tolerance, liver triglyceride content, GK activity, and GK and PFK2 protein and gene expression in fructose-rich diet (FRD) and control rats. After 3 weeks, FRD rats had significantly higher blood glucose, insulin and triglyceride levels, and liver triglyceride content, insulin resistance, and impaired glucose tolerance. FRD rats also had significantly higher GK activity in the cytosolic fraction (18.3 +/- 0.35 vs. 11.27 +/- 0.34 mU/mg protein). Differences in GK protein concentration (116% and 100%) were not significant, suggesting a potentially impaired GK translocation in FRD rats. Although GK transcription level was similar, PFK2 gene expression and protein concentration were 4- and 5-fold higher in the cytosolic fraction of FRD animals. PFK2 immunological blockage significantly decreased GK activity in control and FRD rats; in the latter, this blockage decreased GK activity to control levels. Results suggest that increased liver GK activity might participate in the adaptative response to fructose overload to maintain glucose/triglyceride homeostasis in intact animals. Under these conditions, PFK2 increase would be the main enhancer of GK activity.

Lack of effect of dietary fiber on serum lipids, glucose, and insulin in healthy young men fed high starch diets.

PubMed

Ullrich, I H; Albrink, M J

1982-07-01

Eight healthy young men were fed a 72% carbohydrate high starch diet either high or low in dietary fiber for 4 days in a double cross-over design. Both groups showed a slight transient increase in plasma triglyceride level and a decrease in total and high-density lipoprotein cholesterol. There were few differences in glucose and insulin levels after glucose and meal tolerance tests after each diet. Fasting triglycerides and high-density lipoprotein cholesterol were inversely related at base-line; insulin response to oral glucose was inversely related to high-density lipoprotein cholesterol levels at the end of the study. We conclude that a high carbohydrate high starch diet, whether high or low in fiber, caused little increase in triglycerides, with little difference between the high and low fiber diets. Dietary fiber did not influence the fall in plasma cholesterol or high-density lipoprotein cholesterol concentrations over and above that seen after the low fiber diet.

Association between alpha-fetoprotein and metabolic syndrome in a Chinese asymptomatic population: a cross-sectional study.

PubMed

Chen, Yimin; Zhao, Ying; Feng, Linmin; Zhang, Jie; Zhang, Juanwen; Feng, Guofang

2016-04-27

Metabolic syndrome is closely associated with an increased risk for fatty liver disease morbidity and mortality. Recently, studies have reported that participants with fatty liver disease have higher serum alpha-fetoprotein levels than those without. We investigated the association between alpha-fetoprotein levels and the prevalence of metabolic syndrome in a Chinese asymptomatic population. A cross-sectional study was performed with 7,755 participants who underwent individual health examinations. Clinical and anthropometric parameters were collected and serum alpha-fetoprotein levels and other clinical and laboratory parameters were measured. Logistic regression analysis was used to examine associations between alpha-fetoprotein and metabolic syndrome. Participants with metabolic syndrome had significantly higher (p < 0.001) alpha-fetoprotein levels than those without, though all alpha-fetoprotein levels were within the reference interval. The association between the components of metabolic syndrome (central obesity, elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose) and alpha-fetoprotein levels was evaluated. Alpha-fetoprotein levels in the elevated triglycerides, reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose groups were significantly different (p=0.002, p < 0.001, p=0.020) compared with alpha-fetoprotein in the normal triglycerides, high-density lipoprotein cholesterol, and fasting plasma glucose groups. Logistic regression analyses showed an association between alpha-fetoprotein levels and increased risk for metabolic syndrome, the presence of reduced high-density lipoprotein cholesterol, and elevated fasting plasma glucose, but not with obesity, elevated blood pressure, or triglycerides. These results suggest a significant association between alpha-fetoprotein and metabolic syndrome.

Correlation of CRP, fasting serum triglycerides and obesity as cardiovascular risk factors.

PubMed

Firdous, Samar

2014-05-01

To determine the correlation of C-reactive protein (CRP) with fasting triglycerides (TG) among pre-obese and obese patients without established diagnosis of coronary artery disease (CAD). A comparative cross-sectional study. Mayo Hospital, Lahore, from January to June 2010. Patients with BMI > 23 kg/m2 aged between 18 - 65 years were inducted and above variables were studied. Patients with signs of fluid retention, collagen vascular disease, CAD, patients on corticosteroids, immunomodulators or lipid lowering medications and febrile patients were not recruited. Body mass index was also determined. Independent sample t-test was applied to see the mean difference of age, CRP level and triglycerides level in relation to gender. Chi-square test was used to see the association between qualitative variables. ANOVA was applied to see CRP and fasting serum TG level in relation to BMI categories. Pearson correlation and simple linear regression was applied to see the dependency of CRP and triglycerides with BMI. P-value ² 0.05 was taken as significant. Raised CRP was major finding among all groups of BMI. Most of obese and pre-obese patients were young and middle aged and belonged to pre-obese group followed by class-1 and class-2 obesity. CRP level increased with body mass index. No such trend was observed for triglycerides. There was an intermediate positive correlation between CRP and BMI and triglycerides and BMI showed a weak negative correlation. If BMI increases by 1 unit on the average, CRP rises by 0.239 times and this unit rise was significant. Whereas 1 unit rise increase in triglycerides on the average cause CRP to decrease -0.006 times but this value was insignificant. Raised CRP and high fasting TG were major findings in all age groups especially among young and middle aged people. Obesity, hypertriglyceridemia and raised CRP are interrelated suggesting that obesity is not only linked to hypertriglyceridemia but vascular inflammation among pre-obese and obese without overt diabetes mellitus causes high CRP as well and this can be used as a marker to predict the future risk of CAD. However, in the absence of dyslipidaemia, raised CRP can still be considered as a strong predictor of CAD and stroke.

Triglycerides are negatively correlated with cognitive function in nondemented aging adults.

PubMed

Parthasarathy, Vishnu; Frazier, Darvis T; Bettcher, Brianne M; Jastrzab, Laura; Chao, Linda; Reed, Bruce; Mungas, Dan; Weiner, Michael; DeCarli, Charles; Chui, Helena; Kramer, Joel H

2017-09-01

Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI). Participants were 251 nondemented elderly adults (54% male) with a mean age of 78 (SD = 6.4; range: 62-94) years and a mean education of 15.6 (SD = 2.9; range: 8-23) years. Fasting blood samples were used to detect serum triglyceride and low-density lipoprotein (LDL) levels along with ApoE4 status. DTI was used to determine whole brain fractional anisotropy (FA). Composite executive and memory scores were derived from item response theory. Clinical Dementia Rating (CDR) scores provided informant-based measures of daily functioning. Triglyceride levels were inversely correlated with executive function, but there was no relationship with memory. Controlling for age, gender, and education did not affect this correlation. This relationship persisted after controlling for vascular risk factors like LDL, total cholesterol, CDR and ApoE4 status. Lastly, adding whole-brain FA to the model did not affect the correlation between triglycerides and executive function. Triglyceride levels are inversely correlated with executive function in nondemented elderly adults after controlling for age, education, gender, total cholesterol, LDL, ApoE4 status, CDR, and white-matter microstructure. The fact that the effect of triglycerides on cognition was not clearly mediated by vascular risks or cerebrovascular injury raises questions about widely held assumptions of how triglycerides might impact cognition function. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Triglyceride level

MedlinePlus

... page: //medlineplus.gov/ency/article/003493.htm Triglyceride level To use the sharing features on this page, please enable JavaScript. The triglyceride level is a blood test to measure the amount ...

Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

PubMed

Broedl, Uli C; Lehrke, Michael; Fleischer-Brielmaier, Elisabeth; Tietz, Anne B; Nagel, Jutta M; Göke, Burkhard; Lohse, Peter; Parhofer, Klaus G

2006-05-15

Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T) in perfect linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism.

Effects of total and green vegetable intakes on glycated hemoglobin A1c and triglycerides in elderly patients with type 2 diabetes mellitus: the Japanese Elderly Intervention Trial.

PubMed

Takahashi, Keiko; Kamada, Chiemi; Yoshimura, Hidenori; Okumura, Ryota; Iimuro, Satoshi; Ohashi, Yasuo; Araki, Atsushi; Umegaki, Hiroyuki; Sakurai, Takashi; Yoshimura, Yukio; Ito, Hideki

2012-04-01

Many reports have shown that vegetable intake is effective in inhibiting the onset and progression of diabetes mellitus, although the amount of vegetable intake required to be effective remains as unclear. The present study therefore aimed to clarify the relationship between the amount of vegetable intake and glycated hemoglobin A1c (HbA1c) and other metabolic parameters using male Japanese type 2 diabetic patients aged 65 years or older as subjects. Participants were 417 male type 2 diabetic patients aged 65 years or older enrolled in the Japanese Elderly Diabetes Intervention Trial. Dietary intakes were measured by using the Food Frequency Questionnaires method. The patients were divided into five groups by their daily total vegetable intake (A1: ~100 g, A2: 100~150 g, A3: 150~200 g, A4: 200~300 g, A5: 300 g~), and compared HbA1c and other metabolic parameters. Furthermore, the relationship between daily green vegetable intake and HbA1c and other metabolic parameters were examined among five groups divided by quintile methods. There were significant decreases in HbA1c, triglycerides and waist circumference with an increase of total vegetable intake. A significant decrease of HbA1c levels was observed in patients with a daily total vegetable intake of 150 g or more. Furthermore, there was a significant decrease of serum triglyceride levels in patients with a total vegetable intake of 200 g or more. HbA1c levels showed a decreasing tendency with the increase of green vegetable intake, and HbA1c levels in the Q1 group (green vegetable intake: less than 40 g) was significantly higher than those in the other four groups (anovaP = 0.025). In addition, there were significant decreases of body mass index, triglyceride levels and waist circumference with the increase of green vegetable intake. Triglyceride levels decreased significantly from the Q3 group (green vegetable intake: 70 g or more) to the Q5 group (green vegetable intake: 130 g or more; anovaP = 0.016). In the group with a lower intake of total vegetables and green vegetables, the protein energy ratio decreased significantly. As a result, the fat energy ratio and energy intake tended to increase with the decrease of total and green vegetable intakes. Furthermore, intake of grains, sweets and alcoholic beverages increased with the decrease of total vegetable intake. In contrast, intake of nuts, potatoes, sugar, legumes, fruit, seaweed and fish increased with the increase of total vegetable intake Daily total vegetable intake of 200 g or more, and green vegetable intake of 70 g or more correlated with improved control of HbA1c and triglyceride levels in elderly type 2 diabetes patients through achieving a well-balanced diet. © 2012 Japan Geriatrics Society.

Association between dietary habits, education, serum triglycerides and blood cholesterol among women of Cabildo, Buenos Aires.

PubMed

Schneider, Raul J; Barengo, Noel; Haapala, Irja; Tavella, Marcelo

2006-01-01

A cross sectional study of 107 women between 20 and 69 years old, living in the town of Cabildo, province of Buenos Aires, Argentina, which describes food intake and analyses its relation to their education, blood cholesterol and serum triglyceride levels. A food frequency questionnaire including questions regarding meal patterns and food use were completed by the participants. Questions regarding educational status were included. A nutritional risk score was created from nine food groups. Total blood cholesterol and serum triglyceride levels were determined. Average total blood cholesterol levels of the women who participated in the present study were higher (209 mg/dl) than those recommended by the National Cholesterol Education Program, while triglyceride values remained within the normal range (124 mg/dl). Total blood cholesterol levels increased with age. Bread, biscuits and cakes were consumed on a daily basis by 98% of the participants and dairy products by 92%, these being mainly full-fat. Meat and fast food intake were very high (96% and 100% respectively). Vegetable and fish intakes were higher among the more educated women. Mayonnaise (58%) and butter (43%) are popular as food dressings and bread spreads respectively, and sunflower oil was the most commonly used for cooking by 94% of the participants. Women with low educational levels (less than 7 years) had higher nutritional risk scores, and thus unhealthier dietary habits than those with more years of formal education. No statistically significant association was found between food groups and cholesterol or triglyceride levels.

Serum levels of albumin, triglycerides, total protein and glucose in rats are altered after oral treatment with low doses of 13-cis-retinoic acid or all-trans-retinoic acid.

PubMed

Cisneros, F J; Gough, B J; Patton, R E; Ferguson, S A

2005-01-01

Currently used to treat severe acne, 13-cis-retinoic acid (13-cis-RA) is under investigation for its anticancer effects as is the isomer, all-trans-retinoic acid (all-trans-RA). Here, the effects of oral 13-cis-RA or all-trans-RA treatment on serum chemistry, leptin and adiponectin levels were evaluated. Adult Sprague-Dawley rats were gavaged once daily for 7 consecutive days with 13-cis-RA (7.5 or 15 mg kg(-1)), all-trans-RA (10 or 15 mg kg(-1)) (n=24/sex/dose), or soy oil (n=16/sex) and blood was sampled 30-480 min after the last gavage. The body weight was unaffected; however, the liver/body weight ratios were increased by both doses of all-trans-RA. Sex differences were noted for levels of cholesterol, creatine, triglycerides, albumin, alanine aminotransferase and total protein. Both doses of all-trans-RA reduced albumin levels to approximately 90% of the control and total protein levels to approximately 93% of the control while substantially elevating triglyceride levels to approximately 66%-99% above the control. Additionally, triglyceride levels of the 15 mg kg(-1) 13-cis RA group were approximately 62% higher than the controls and total protein levels were approximately 5% less. Glucose levels were affected by sex and RA treatment in that males treated with 15 mg kg(-1) of 13-cis-RA or 10 mg kg(-1) all-trans-RA had lower (13%-19%) levels than the same-sex controls; however, females were not similarly affected. Neither 13-cis-RA nor all-trans-RA treatment had significant effects on the levels of blood urea nitrogen, aspartate amino transferase, leptin or adiponectin. On a mg kg(-1) basis, all-trans-RA was more potent than 13-cis-RA. These results replicate previous findings of RA-induced increased triglyceride levels. Additionally, several new findings indicate there may be sex-specific effects of RA treatment. Finally, neither treatment appeared to alter the typical diurnal cycles of these endpoints. Copyright (c) 2005 John Wiley & Sons, Ltd.

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.

Marked hypertriglyceridemia in a woman receiving metoprolol succinate.

PubMed

Kim, Yeunjung; Miller, Michael

2014-01-01

β-blockers are commonly used therapies after acute myocardial infarction and in the management of congestive heart failure and hypertension. We report a case of a middle-aged woman with a history of mild hypertension who was placed on metoprolol succinate. Before initiation of the β-blocker, her triglyceride level was in the borderline-high range (150-199 mg/dL). On treatment, her triglyceride levels exceeded 1000 mg/dL. She developed fatigue and mild abdominal discomfort but without biochemical evidence of pancreatitis. After discontinuation of metoprolol succinate, her triglyceride levels receded. This case illustrates an uncommon side effect with a very commonly used therapy in clinical practice. Clinicians should closely evaluate medications and/or other therapies in patients presenting with new-onset hypertriglyceridemia especially when levels are sufficiently elevated to pose increased risk of pancreatitis. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Loss-of-function mutations in APOC3 and risk of ischemic vascular disease.

PubMed

Jørgensen, Anders Berg; Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Tybjærg-Hansen, Anne

2014-07-03

High plasma levels of nonfasting triglycerides are associated with an increased risk of ischemic cardiovascular disease. Whether lifelong low levels of nonfasting triglycerides owing to mutations in the gene encoding apolipoprotein C3 (APOC3) are associated with a reduced risk of ischemic cardiovascular disease in the general population is unknown. Using data from 75,725 participants in two general-population studies, we first tested whether low levels of nonfasting triglycerides were associated with reduced risks of ischemic vascular disease and ischemic heart disease. Second, we tested whether loss-of-function mutations in APOC3, which were associated with reduced levels of nonfasting triglycerides, were also associated with reduced risks of ischemic vascular disease and ischemic heart disease. During follow-up, ischemic vascular disease developed in 10,797 participants, and ischemic heart disease developed in 7557 of these 10,797 participants. Participants with nonfasting triglyceride levels of less than 1.00 mmol per liter (90 mg per deciliter) had a significantly lower incidence of cardiovascular disease than those with levels of 4.00 mmol per liter (350 mg per deciliter) or more (hazard ratio for ischemic vascular disease, 0.43; 95% confidence interval [CI], 0.35 to 0.54; hazard ratio for ischemic heart disease, 0.40; 95% CI, 0.31 to 0.52). Heterozygosity for loss-of-function mutations in APOC3, as compared with no APOC3 mutations, was associated with a mean reduction in nonfasting triglyceride levels of 44% (P<0.001). The cumulative incidences of ischemic vascular disease and ischemic heart disease were reduced in heterozygotes as compared with noncarriers of APOC3 mutations (P=0.009 and P=0.05, respectively), with corresponding risk reductions of 41% (hazard ratio, 0.59; 95% CI, 0.41 to 0.86; P=0.007) and 36% (hazard ratio, 0.64; 95% CI, 0.41 to 0.99; P=0.04). Loss-of-function mutations in APOC3 were associated with low levels of triglycerides and a reduced risk of ischemic cardiovascular disease. (Funded by the European Union and others.).

Prospective clinical study reveals significant reduction in triglyceride level and white blood cell count after liposuction and abdominoplasty and no change in cholesterol levels.

PubMed

Swanson, Eric

2011-09-01

Triglyceride levels of 150 mg/dL or greater are known to be associated with an increased cardiovascular risk and metabolic syndrome. This study investigated the effect of liposuction and abdominoplasty on lipid levels, complete blood count, and other parameters. A prospective study was undertaken among 322 consecutive patients (270 women and 52 men) who presented for liposuction (n = 229), abdominoplasty with liposuction (n = 87), and abdominoplasty without liposuction (n = 6). The mean body mass index was 26.6 kg/m2 (range, 18.6 to 44.1 kg/m2). Ultrasonic liposuction using a superwet infusion technique was used in all cases, usually treating the lower body in women (64.4 percent) and the trunk in men (86.5 percent). Mean weight loss 3 months after liposuction was 2.2 lbs for liposuction alone (p < 0.001) and 4.2 lbs for liposuction and abdominoplasty (p < 0.05). Mean fasting triglyceride level decreased 25.7 percent after liposuction (p < 0.001). The triglyceride level decreased 43.0 percent (n = 56, p < 0.001) after liposuction in patients with preoperative levels of 150 mg/dl or greater. There was a significant decrease in white cell count after both liposuction and liposuction/abdominoplasty (p < 0.001). There were no significant changes in total, low-density lipoprotein, or high-density lipoprotein cholesterol. Fasting glucose was unchanged. A significant (p < 0.001) reduction in triglyceride level in patients with elevated preoperative levels and a significant decrease in leukocyte count (p < 0.001) are favorable metabolic effects of liposuction and liposuction/abdominoplasty. Cholesterol levels are unaffected. Therapeutic, IV.

Omega-3 carboxylic acids (Epanova): a review of its use in patients with severe hypertriglyceridemia.

PubMed

Blair, Hannah A; Dhillon, Sohita

2014-10-01

Omega-3 carboxylic acids (Epanova) [OM3-CA] is the first free fatty acid form of long-chain marine omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid being the most abundant) to be approved by the US FDA as an adjunct to diet to lower triglyceride levels in patients with severe hypertriglyceridemia (≥ 500 mg/dL). Oral OM3-CA has greater bioavailability than ethyl ester forms of omega-3 and, unlike omega-3 acid ethyl esters, does not require co-ingestion of a high-fat meal, as it does not need pancreatic enzyme activity for absorption. In the 12-week EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial, OM3-CA 2 or 4 g/day significantly reduced serum triglyceride levels relative to placebo. Other lipid parameters, including non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol, and very low-density lipoprotein cholesterol (VLDL-C) levels, were also reduced significantly with OM3-CA relative to placebo. Low-density lipoprotein cholesterol levels were increased significantly with OM3-CA relative to placebo; however, these increases were not accompanied by increases in the circulating concentrations of non-HDL-C, VLDL-C, or apolipoprotein B. OM3-CA was generally well tolerated in this study, with most adverse events being of mild or moderate severity. Although additional comparative data are needed to position OM3-CA with respect to other formulations of omega-3 fatty acids, current evidence suggests that OM3-CA is a useful addition to the treatment options available for patients with severe hypertriglyceridemia.

Enhanced serum cholesterol and triglyceride levels in bulimia nervosa: relationships to psychiatric comorbidity, psychopathology and hormonal variables.

PubMed

Monteleone, Palmiero; Santonastaso, Paolo; Pannuto, Marilena; Favaro, Angela; Caregaro, Lorenza; Castaldo, Eloisa; Zanetti, Tatiana; Maj, Mario

2005-04-30

Increased levels of cholesterol have been reported in patients with bulimia nervosa (BN), but all but one of the published studies were performed on non-fasting subjects, which limits the interpretation of this finding. Moreover, the relationships between serum lipids and comorbid psychiatric disorders or bulimic psychopathology have scarcely been investigated. We measured serum levels of total cholesterol, triglycerides, glucose, 17beta-estradiol and thyroid hormones in 75 bulimic women and 64 age-matched healthy females after an overnight fast. Compared with healthy women, bulimic patients exhibited significantly enhanced serum levels of cholesterol and triglycerides, but similar values of glucose, 17beta-estradiol, FT3 and FT4. No significant differences emerged in these variables between patients with or without comorbid depression, borderline personality disorder or lifetime anorexia nervosa. Circulating cholesterol was positively correlated to the patients' drive for thinness, ineffectiveness, enteroceptive awareness and impulse regulation sub-item scores of the Eating Disorder Inventory-2. These findings confirm that BN is associated with increased levels of serum lipids. This alteration may be involved in the pathophysiology of certain psychopathological characteristics of BN and cannot be explained by the co-occurrence of other psychiatric disorders.

Omega-3 Fatty Acid Deficiency Increases Stearoyl-CoA Desaturase Expression and Activity Indices in Rat Liver: Positive Association with Non-Fasting Plasma Triglyceride Levels

PubMed Central

Hofacer, Rylon; Magrisso, I. Jack; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Benoit, Stephen C.; McNamara, Robert K.

2011-01-01

Although omega-3 (n-3) fatty acids negatively regulate triglyceride biosynthesis, the mechanisms mediating this effect are poorly understood, and emerging evidence suggests that stearoyl-CoA desaturase (Scd1) is required for de novo triglyceride biosynthesis. To investigate this mechanism, we determined the effects of perinatal n-3 deficiency and postnatal repletion on rat liver Scd1 mRNA expression and activity indices (liver 16:1/16:0 & 18:1/18:0 ratios), and determined relationships with postprandial (non-fasting) plasma triglyceride levels. Rats were fed conventional diets with or without the n-3 fatty acid precursor α-linolenic acid (ALA, 18:3n-3) during perinatal development (E0-P100), and a subset of rats fed the ALA− diet were switched to the ALA+ diet post-weaning (P21-P100, repletion). Compared with controls, rats fed the ALA− diet exhibited significantly lower liver long-chain n-3 fatty acid compositions and elevations in monounsaturated fatty acid composition, both of which were normalized in repleted rats. Liver Scd1 mRNA expression and activity indices (16:1/16:0 & 18:1/18:0 ratios) were significantly greater in n-3 deficient rats compared with controls and repleted rats. Among all rats, liver Scd1 mRNA expression was positively correlated with liver 18:1/18:0 and 16:1/16:0 ratios. Plasma triglyceride levels, but not glucose or insulin levels, were significantly greater in n-3 deficient rats compared with controls and repleted rats. Liver Scd1 mRNA expression and activity indices were positively correlated with plasma triglyceride levels. These preclinical findings demonstrate that n-3 fatty acid status is an important determinant of liver Scd1 mRNA expression and activity, and suggest that down-regulation of Scd1 is a mechanism by which n-3 fatty acids repress constitutive triglyceride biosynthesis. PMID:22047910

Apolipoprotein A5: A newly identified gene impacting plasmatriglyceride levels in humans and mice

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

Pennacchio, Len A.; Rubin, Edward M.

2002-09-15

Apolipoprotein A5 (APOA5) is a newly described member of theapolipoprotein gene family whose initial discovery arose from comparativesequence analysis of the mammalian APOA1/C3/A4 gene cluster. Functionalstudies in mice indicated that alteration in the level of APOA5significantly impacted plasma triglyceride concentrations. Miceover-expressing human APOA5 displayed significantly reducedtriglycerides, while mice lacking apoA5 had a large increase in thislipid parameter. Studies in humans have also suggested an important rolefor APOA5 in determining plasma triglyceride concentrations. In theseexperiments, polymorphisms in the human gene were found to define severalcommon haplotypes that were associated with significant changes intriglyceride concentrations in multiple populations. Several separateclinical studies havemore » provided consistent and strong support for theeffect with 24 percent of Caucasians, 35 percent of African-Americans and53 percent of Hispanics carrying APOA5 haplotypes associated withincreased plasma triglyceride levels. In summary, APOA5 represents anewly discovered gene involved in triglyceride metabolism in both humansand mice whose mechanism of action remains to be deciphered.« less

Rapamycin up-regulates triglycerides in hepatocytes by down-regulating Prox1.

PubMed

Kwon, Sora; Jeon, Ji-Sook; Kim, Su Bin; Hong, Young-Kwon; Ahn, Curie; Sung, Jung-Suk; Choi, Inho

2016-02-27

Although the prolonged use of rapamycin may cause unwanted side effects such as hyperlipidemia, the underlying mechanism remains unknown. Prox1 is a transcription factor responsible for the development of several tissues including lymphatics and liver. There is growing evidences that Prox1 participates in metabolism in addition to embryogenesis. However, whether Prox1 is directly related to lipid metabolism is currently unknown. HepG2 human hepatoma cells were treated with rapamycin and total lipids were analyzed by thin layer chromatography. The effect of rapamycin on the expression of Prox1 was determined by western blotting. To investigate the role of Prox1 in triglycerides regulation, siRNA and overexpression system were employed. Rapamycin was injected into mice for 2 weeks and total lipids and proteins in liver were measured by thin layer chromatography and western blot analysis, respectively. Rapamycin up-regulated the amount of triglyceride and down-regulated the expression of Prox1 in HepG2 cells by reducing protein half-life but did not affect its transcript. The loss-of-function of Prox1 was coincident with the increase of triglycerides in HepG2 cells treated with rapamycin. The up-regulation of triglycerides by rapamycin in HepG2 cells reverted to normal levels by the compensation of Prox1 using the overexpression system. Rapamycin also down-regulated Prox1 expression but increased triglycerides in mouse liver. This study suggests that rapamycin can increase the amount of triglycerides by down-regulating Prox1 expression in hepatocytes, which means that the mammalian target of rapamycin (mTOR) signaling is important for the regulation of triglycerides by maintaining Prox1 expression.

Structured triglyceride vehicles for oral delivery of halofantrine: examination of intestinal lymphatic transport and bioavailability in conscious rats.

PubMed

Holm, René; Porter, Christopher J H; Müllertz, Anette; Kristensen, Henning G; Charman, William N

2002-09-01

To compare the influence of triglyceride vehicle intramolecular structure on the intestinal lymphatic transport and systemic absorption of halofantrine in conscious rats. Conscious, lymph cannulated and nonlymph cannulated rats were dosed orally with three structurally different triglycerides; sunflower oil, and two structured triglycerides containing different proportion and position of medium-(M) and long-chain (L) fatty acids on the glycerol backbone. The two structured triglycerides were abbreviated MLM and LML to reflect the structural position on the glycerol. The concentration of halofantrine in blood and lymph samples was analyzed by HPLC. Both the lymphatic transport and the total absorption of halofantrine were enhanced by the use the MLM triglyceride. The estimated total absorption of halofantrine in the lymph cannulated animals was higher than in the nonlymph cannulated animals, and this was most pronounced for the animals dosed with the structured triglycerides. Using MLM as vehicle increases the portal absorption of halofantrine and results in similar lymphatic transport levels when compared to sunflower oil. Total absorption when assessed as absorption in the blood plus lymphatic transport for halofantrine after administration in the MLM triglyceride was higher than after administration in sunflower oil.

Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro.

PubMed

Nishimoto, Tomoyuki; Amano, Yuichiro; Tozawa, Ryuichi; Ishikawa, Eiichiro; Imura, Yoshimi; Yukimasa, Hidefumi; Sugiyama, Yasuo

2003-07-01

1. Squalene synthase is the enzyme that converts farnesyl pyrophosphate to squalene in the cholesterol biosynthesis pathway. We examined the lipid-lowering properties of 1-[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-acetic acid (TAK-475), a novel squalene synthase inhibitor. 2. TAK-475 inhibited hepatic cholesterol biosynthesis in rats (ED(50), 2.9 mg kg(-1)) and showed lipid-lowering effects in beagle dogs, marmosets, cynomolgus monkeys and Wistar fatty rats. 3. In marmosets, TAK-475 (30, 100 mg kg(-1), p.o., for 4 days) lowered both plasma non-high-density lipoprotein (HDL) cholesterol and triglyceride, but did not affect plasma HDL cholesterol. On the other hand, atorvastatin (10, 30 mg kg(-1), p.o., for 4 days) lowered the levels of all these lipids. A correlation between decrease in triglyceride and increase in HDL cholesterol was observed, and TAK-475 increased HDL cholesterol with a smaller decrease in triglyceride than did atorvastatin. 4. TAK-475 (60 mg kg(-1), p.o., for 15 days) suppressed the rate of triglyceride secretion from the liver in hypertriglyceridemic Wistar fatty rats, which show an enhanced triglyceride secretion rate from the liver compared with their lean littermates. 5. In HepG2 cells, TAK-475 and its pharmacologically active metabolite, T-91485, increased the binding of (125)I-low-density lipoprotein (LDL) to LDL receptors. 6. These results suggest that TAK-475 has clear hypolipidemic effects in animals via inhibition of hepatic triglyceride secretion and upregulation of LDL receptors, and that TAK-475 might increase HDL cholesterol by decreasing triglyceride. Thus, TAK-475 is expected to be useful for the treatment of dyslipidemia.

Lipid-lowering properties of TAK-475, a squalene synthase inhibitor, in vivo and in vitro

PubMed Central

Nishimoto, Tomoyuki; Amano, Yuichiro; Tozawa, Ryuichi; Ishikawa, Eiichiro; Imura, Yoshimi; Yukimasa, Hidefumi; Sugiyama, Yasuo

2003-01-01

Squalene synthase is the enzyme that converts farnesyl pyrophosphate to squalene in the cholesterol biosynthesis pathway. We examined the lipid-lowering properties of 1-[[(3R,5S)-1-(3-acetoxy-2,2-dimethylpropyl)-7-chloro-5-(2,3-dimethoxyphenyl)-2-oxo-1,2,3,5-tetrahydro-4,1-benzoxazepin-3-yl]acetyl]piperidine-4-acetic acid (TAK-475), a novel squalene synthase inhibitor. TAK-475 inhibited hepatic cholesterol biosynthesis in rats (ED50, 2.9 mg kg−1) and showed lipid-lowering effects in beagle dogs, marmosets, cynomolgus monkeys and Wistar fatty rats. In marmosets, TAK-475 (30, 100 mg kg−1, p.o., for 4 days) lowered both plasma non-high-density lipoprotein (HDL) cholesterol and triglyceride, but did not affect plasma HDL cholesterol. On the other hand, atorvastatin (10, 30 mg kg−1, p.o., for 4 days) lowered the levels of all these lipids. A correlation between decrease in triglyceride and increase in HDL cholesterol was observed, and TAK-475 increased HDL cholesterol with a smaller decrease in triglyceride than did atorvastatin. TAK-475 (60 mg kg−1, p.o., for 15 days) suppressed the rate of triglyceride secretion from the liver in hypertriglyceridemic Wistar fatty rats, which show an enhanced triglyceride secretion rate from the liver compared with their lean littermates. In HepG2 cells, TAK-475 and its pharmacologically active metabolite, T-91485, increased the binding of 125I-low-density lipoprotein (LDL) to LDL receptors. 6 These results suggest that TAK-475 has clear hypolipidemic effects in animals via inhibition of hepatic triglyceride secretion and upregulation of LDL receptors, and that TAK-475 might increase HDL cholesterol by decreasing triglyceride. Thus, TAK-475 is expected to be useful for the treatment of dyslipidemia. PMID:12839864

Hipertriglyceridemia induced acute pancreatitis in pregnancy.

PubMed

Mañas García, María Dolores; Marchán Carranza, Enrique; Galiana Gómez Del Pulgar, Jesús; Fernández de Bobadilla Pascual, Belén

Hypertrigliceridemia is the third most common cause of acute pancreatitis. The risk of developing acute pancreatitis is 5% in healthy patients and 4% during pregnancy with triglyceride levels >1,000mg/dl. During pregnancy there are changes in the lipid profile that increase between two and four times triglyceride levels. Its increase in excessive form produces an oxidative environment with injury of the endothelium and appearance of complications such as preeclampsia or pancreatitis. We present the case of a pregnant woman with pancreatitis secondary to hypertriglyceridemia. Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Investigating a Liver Fat: Arterial Stiffening Pathway in Adult and Childhood Obesity.

PubMed

Rider, Oliver J; Banerjee, Rajarshi; Rayner, Jennifer J; Shah, Ravi; Murthy, Venkatesh L; Robson, Matthew D; Neubauer, Stefan

2016-01-01

To investigate the relationship between hepatic fat content, circulating triglyceride levels and aortic stiffness in adult and childhood obesity. Seventy-seven adults and 18 children across a wide range of body mass index (18.5-52.6 kg/m(2); percentile 8-100) with no identifiable cardiac risk factors underwent; 1H- magnetic resonance spectroscopy to quantify hepatic fat content and magnetic resonance imaging to assess aortic pulse wave velocity (PWV) and regional distensibility. In adults, multivariable regression showed age (β=0.09; P=0.02), liver fat (β=2.5; P=0.04), and serum triglyceride (β=0.47; P=0.01) to be independent predictors of PWV. Age and blood pressure-adjusted, moderated regression showed that 43% of the total negative effect of hepatic fat on PWV is attributable to indirect effects via increased triglyceride (P=0.005). In addition, regional distensibility was positively correlated with hepatic fat (ascending; r=-0.35; descending, r=-0.23; abdominal, r=-0.41; all P<0.001). Similar to that seen in adults, PWV (r=0.72; P<0.001) and abdominal regional distensibility (r=-0.52; P<0.001) were correlated with liver fat in children. Increasing age, liver fat, and triglyceride are all related to increased aortic stiffness in adults. Even when controlling for the effects of age and blood pressure, hepatic fat has a negative effect on PWV, with substantial indirect effect occurring via increased circulating triglyceride level. This relationship between hepatic fat and aortic stiffness occurs early in the obesity process and is also seen in children. As such, hepatic fat content is a potential therapeutic target to treat the elevated vascular risk in obesity. © 2015 American Heart Association, Inc.

Lipid levels and changes in body fat distribution in treatment-naive, HIV-1-Infected adults treated with rilpivirine or Efavirenz for 96 weeks in the ECHO and THRIVE trials.

PubMed

Tebas, Pablo; Sension, Michael; Arribas, José; Duiculescu, Dan; Florence, Eric; Hung, Chien-Ching; Wilkin, Timothy; Vanveggel, Simon; Stevens, Marita; Deckx, Henri

2014-08-01

Pooled ECHO/THRIVE lipid and body fat data are presented from the ECHO (Efficacy Comparison in Treatment-Naïve, HIV-Infected Subjects of TMC278 and Efavirenz) and THRIVE (TMC278 Against HIV, in a Once-Daily Regimen Versus Efavirenz) trials. We assessed the 96-week effects on lipids, adverse events (AEs), and body fat distribution (dual-energy x-ray absorptiometry) of rilpivirine (RPV) and EFV plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTIs) in treatment-naive adults infected with human immunodeficiency virus type 1 (HIV-1). Rilpivirine produced minimal changes in total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Compared with RPV, EFV significantly (P < .001) increased lipid levels. Decreases in the TC/HDL-C ratio were similar with RPV and EFV. Background N[t]RTI affected RPV-induced lipid changes; all levels increased with zidovudine/lamivudine (3TC) and abacavir/3TC (except triglycerides, which were unchanged). With emtricitabine/tenofovir, levels of HDL-C were increased, TC and LDL-C were unchanged, and triglycerides were decreased. With EFV, lipid levels increased in each N[t]RTI subgroup (except triglycerides were unchanged with abacavir/3TC). Fewer (P < .001) RPV-treated patients than EFV-treated patients had TC, LDL-C, and triglyceride levels above National Cholesterol Education Program cutoffs. More RPV- than EFV-treated patients had HDL-C values below these cutoffs (P = .02). Dyslipidemia AEs were less common with RPV than with EFV. Similar proportions of patients had a ≥10% decrease in limb fat (16% with RPV and 17% with EFV). Limb fat was significantly (P < .001) increased to a similar extent (by 12% with RPV and 11% with EFV). At week 96, patients receiving zidovudine/3TC had lost limb fat, and those receiving emtricitabine/tenofovir had gained it. Over the course of 96 weeks, RPV-based therapy was associated with lower increases in lipid parameters and fewer dyslipidemia AEs than EFV-based treatment. Body fat distribution changes were similar between treatments. The N[t]RTI regimen affected lipid and body fat distribution changes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Lipid Absorption Defects in Intestine-specific Microsomal Triglyceride Transfer Protein and ATP-binding Cassette Transporter A1-deficient Mice*

PubMed Central

Iqbal, Jahangir; Parks, John S.; Hussain, M. Mahmood

2013-01-01

We have previously described apolipoprotein B (apoB)-dependent and -independent cholesterol absorption pathways and the role of microsomal triglyceride transfer protein (MTP) and ATP-binding cassette transporter A1 (ABCA1) in these pathways. To assess the contribution of these pathways to cholesterol absorption and to determine whether there are other pathways, we generated mice that lack MTP and ABCA1, individually and in combination, in the intestine. Intestinal deletions of Mttp and Abca1 decreased plasma cholesterol concentrations by 45 and 24%, respectively, whereas their combined deletion reduced it by 59%. Acute cholesterol absorption was reduced by 28% in the absence of ABCA1, and it was reduced by 92–95% when MTP was deleted in the intestine alone or together with ABCA1. MTP deficiency significantly reduced triglyceride absorption, although ABCA1 deficiency had no effect. ABCA1 deficiency did not affect cellular lipids, but Mttp deficiency significantly increased intestinal levels of triglycerides and free fatty acids. Accumulation of intestinal free fatty acids, but not triglycerides, in Mttp-deficient intestines was prevented when mice were also deficient in intestinal ABCA1. Combined deficiency of these genes increased intestinal fatty acid oxidation as a consequence of increased expression of peroxisome proliferator-activated receptor-γ (PPARγ) and carnitine palmitoyltransferase 1α (CPT1α). These studies show that intestinal MTP and ABCA1 are critical for lipid absorption and are the main determinants of plasma and intestinal lipid levels. Reducing their activities might lower plasma lipid concentrations. PMID:24019513

Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

NASA Astrophysics Data System (ADS)

Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

2006-03-01

Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

The rs2516839 Polymorphism of the USF1 Gene May Modulate Serum Triglyceride Levels in Response to Cigarette Smoking

PubMed Central

Niemiec, Pawel; Nowak, Tomasz; Iwanicki, Tomasz; Gorczynska-Kosiorz, Sylwia; Balcerzyk, Anna; Krauze, Jolanta; Grzeszczak, Wladyslaw; Wiecha, Maria; Zak, Iwona

2015-01-01

Single nucleotide polymorphisms (SNPs) of the USF1 gene (upstream stimulatory factor 1) influence plasma lipid levels. This study aims to determine whether USF1 SNPs interact with traditional risk factors of atherosclerosis to increase coronary artery disease (CAD) risk. In the present study serum lipid levels and USF1 gene polymorphisms (rs2516839 and rs3737787) were determined in 470 subjects: 235 patients with premature CAD and 235 controls. A trend of increasing triglycerides (TG) levels in relation to the C allele dose of rs2516839 SNP was observed. The synergistic effect of cigarette smoking and C allele carrier state on CAD risk was also found (SIM = 2.69, p = 0.015). TG levels differentiated significantly particular genotypes in smokers (1.53 mmol/L for TT, 1.80 mmol/L for CT and 2.27 mmol/L for CC subjects). In contrast, these differences were not observed in the non-smokers subgroup (1.57 mmol/L for TT, 1.46 mmol/L for CT and 1.49 mmol/L for CC subjects). In conclusion, the rs2516839 polymorphism may modulate serum triglyceride levels in response to cigarette smoking. Carriers of the C allele seem to be particularly at risk of CAD, when exposed to cigarette smoking. PMID:26068452

A comparison of long-chain triglycerides and medium-chain triglycerides on weight loss and tumour size in a cachexia model.

PubMed Central

Tisdale, M. J.; Brennan, R. A.

1988-01-01

A comparison has been made between the ability of long-chain triglycerides (LCT) and medium-chain triglycerides (MCT) to prevent weight loss induced by the cachexia-inducing colon adenocarcinoma (MAC16) and to reduce tumour size. There was no difference in calorie consumption or nitrogen intake between the various groups. When compared with a normal control high carbohydrate, low fat diet, animals fed MCT showed a reduced weight loss and a marked reduction in tumour size. In contrast neither weight loss nor tumour size differed significantly from the controls in animals fed the LCT diet. An elevated plasma level of 3-hydroxybuturate was found only in the animals fed the MCT diets. Administration of LCT caused an increase in the plasma level of FFA, which was not observed in the MCT group. These results suggest that diets containing MCT would provide the best ketogenic regime to reverse the weight loss in cancer cachexia with a concomitant reduction in tumour size. PMID:3219268

The autonomic nervous system regulates postprandial hepatic lipid metabolism.

PubMed

Bruinstroop, Eveline; la Fleur, Susanne E; Ackermans, Mariette T; Foppen, Ewout; Wortel, Joke; Kooijman, Sander; Berbée, Jimmy F P; Rensen, Patrick C N; Fliers, Eric; Kalsbeek, Andries

2013-05-15

The liver is a key organ in controlling glucose and lipid metabolism during feeding and fasting. In addition to hormones and nutrients, inputs from the autonomic nervous system are also involved in fine-tuning hepatic metabolic regulation. Previously, we have shown in rats that during fasting an intact sympathetic innervation of the liver is essential to maintain the secretion of triglycerides by the liver. In the current study, we hypothesized that in the postprandial condition the parasympathetic input to the liver inhibits hepatic VLDL-TG secretion. To test our hypothesis, we determined the effect of selective surgical hepatic denervations on triglyceride metabolism after a meal in male Wistar rats. We report that postprandial plasma triglyceride concentrations were significantly elevated in parasympathetically denervated rats compared with control rats (P = 0.008), and VLDL-TG production tended to be increased (P = 0.066). Sympathetically denervated rats also showed a small rise in postprandial triglyceride concentrations (P = 0.045). On the other hand, in rats fed on a six-meals-a-day schedule for several weeks, a parasympathetic denervation resulted in >70% higher plasma triglycerides during the day (P = 0.001), whereas a sympathetic denervation had no effect. Our results show that abolishing the parasympathetic input to the liver results in increased plasma triglyceride levels during postprandial conditions.

[Relationship between lipid alterations during pregnancy and adverse pregnancy outcomes].

PubMed

Ferriols, Elena; Rueda, Carolina; Gamero, Rocío; Vidal, Mar; Payá, Antonio; Carreras, Ramón; Flores-le Roux, Juana A; Pedro-Botet, Juan

Lipids play an important role during pregnancy, and in this period major changes occur in lipoprotein metabolism. During the third trimester plasma cholesterol and triglyceride levels are substantially increased, returning to normal after delivery. Described associations between increased morbidity during pregnancy and excessive increases in plasma cholesterol and triglycerides. For this reason we have reviewed the relationship between lipid alterations, preeclampsia, gestational diabetes and preterm birth. The overall metabolic control can improve pregnancy outcomes, and the assessment of supraphysiological changes in lipid profile will classify pregnancy risk at a higher level, which would entail a stricter control. Copyright © 2015 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Obesity and chronic stress are able to desynchronize the temporal pattern of serum levels of leptin and triglycerides.

PubMed

de Oliveira, Carla; Scarabelot, Vanessa Leal; de Souza, Andressa; de Oliveira, Cleverson Moraes; Medeiros, Liciane Fernandes; de Macedo, Isabel Cristina; Marques Filho, Paulo Ricardo; Cioato, Stefania Giotti; Caumo, Wolnei; Torres, Iraci L S

2014-01-01

Disruption of the circadian system can lead to metabolic dysfunction as a response to environmental alterations. This study assessed the effects of the association between obesity and chronic stress on the temporal pattern of serum levels of adipogenic markers and corticosterone in rats. We evaluated weekly weight, delta weight, Lee index, and weight fractions of adipose tissue (mesenteric, MAT; subcutaneous, SAT; and pericardial, PAT) to control for hypercaloric diet-induced obesity model efficacy. Wistar rats were divided into four groups: standard chow (C), hypercaloric diet (HD), stress plus standard chow (S), and stress plus hypercaloric diet (SHD), and analyzed at three time points: ZT0, ZT12, and ZT18. Stressed animals were subjected to chronic stress for 1h per day, 5 days per week, during 80 days. The chronic exposure to a hypercaloric diet was an effective model for the induction of obesity and metabolic syndrome, increasing delta weight, Lee index, weight fractions of adipose tissue, and triglycerides and leptin levels. We confirmed the presence of a temporal pattern in the release of triglycerides, corticosterone, leptin, and adiponectin in naïve animals. Chronic stress reduced delta weight, MAT weight, and levels of triglycerides, total cholesterol, and leptin. There were interactions between chronic stress and obesity and serum total cholesterol levels, between time points and obesity and adiponectin and corticosterone levels, and between time points and chronic stress and serum leptin levels. In conclusion, both parameters were able to desynchronize the temporal pattern of leptin and triglyceride release, which could contribute to the development of metabolic diseases such as obesity and metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

DEAE-Dextran in the treatment of primary hypercholesterolemia and/or hypercholesterolemia combined with hypertriglyceridemia. A multicentric randomized study on the efficacy of DEAE-Dextran compared with Cholestyramine.

PubMed

Fedele, F

2003-01-01

This study was carried out to verify the therapeutic homogeneity between DEAE-Dextran and Cholestyramine. Blood levels of total cholesterol, HDL, LDL and triglycerides were evaluated in 202 patients affected by dyslipidemia and treated with DEAD-D at 2.5 g/day or with Cholestyramine at 12 g/day for 30 days. At the end of treatment both drugs caused significant reduction of total cholesterol, LDL and triglycerides blood levels; DEAD-D was generally more effective than Cholestyramine, in particular on triglycerides values (30.6% and 13.7% of reduction respectively), and produced also a significant increase in HDL cholesterol, differently from Cholestyramine that was ineffective on this parameter.

Do genetic modifiers of high-density lipoprotein cholesterol and triglyceride levels also modify their response to a lifestyle intervention in the setting of obesity and type-2 diabetes mellitus?: The Action for Health in Diabetes (Look AHEAD) study.

PubMed

Huggins, Gordon S; Papandonatos, George D; Erar, Bahar; Belalcazar, L Maria; Brautbar, Ariel; Ballantyne, Christie; Kitabchi, Abbas E; Wagenknecht, Lynne E; Knowler, William C; Pownall, Henry J; Wing, Rena R; Peter, Inga; McCaffery, Jeanne M

2013-08-01

High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies as associated with HDL-C or triglyceride levels modify 1-year treatment response to an intensive lifestyle intervention, relative to a usual care of diabetes mellitus support and education. We evaluated 82 single-nucleotide polymorphisms, which represent 31 loci demonstrated by genome-wide association studies to be associated with HDL-C and triglycerides, in 3561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with intensive lifestyle intervention (P=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (P=0.047 and 0.046, respectively). The fatty acid desaturase-2 rs1535 variant, associated with low baseline HDL-C (P=0.017), was associated with HDL-C increases with intensive lifestyle intervention (0.0037) and had a nominal treatment interaction (P=0.035). Apolipoprotein B (rs693) and LIPC (rs8034802) single-nucleotide polymorphisms showed nominally significant associations with HDL-C and triglyceride changes with intensive lifestyle intervention and a treatment interaction (P<0.05). Phosphatidylglycerophosphate synthase-1 single-nucleotide polymorphisms (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (P=0.0009). This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight or obese individuals with diabetes mellitus. The effects of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention.

Do Genetic Modifiers of HDL-C and Triglyceride Levels also Modify Their Response to a Lifestyle Intervention in the Setting of Obesity and Type-2 Diabetes Mellitus? The Look AHEAD Study

PubMed Central

Huggins, Gordon S.; Papandonatos, George D.; Erar, Bahar; Belalcazar, L. Maria; Brautbar, Ariel; Ballantyne, Christie; Kitabchi, Abbas E.; Wagenknecht, Lynne E.; Knowler, William C.; Pownall, Henry J.; Wing, Rena R.; Peter, Inga; McCaffery, Jeanne M.

2014-01-01

Background High-density lipoprotein cholesterol (HDL-C) and triglycerides are cardiovascular risk factors susceptible to lifestyle behavior modification and genetics. We hypothesized that genetic variants identified by genome-wide association studies (GWASs) as associated with HDL-C or triglyceride levels will modify 1-year treatment response to an intensive lifestyle intervention (ILI), relative to a usual care of diabetes support and education (DSE). Methods and Results We evaluated 82 SNPs, representing 31 loci demonstrated by GWAS to be associated with HDL-C and/or triglycerides, in 3,561 participants who consented for genetic studies and met eligibility criteria. Variants associated with higher baseline HDL-C levels, cholesterol ester transfer protein (CETP) rs3764261 and hepatic lipase (LIPC) rs8034802, were found to be associated with HDL-C increases with ILI (p=0.0038 and 0.013, respectively) and had nominally significant treatment interactions (p=0.047 and 0.046, respectively). The fatty acid desaturase-2 (FADS-2) rs1535 variant, associated with low baseline HDL-C (p=0.017), was associated with HDL-C increases with ILI (0.0037) and had a nominal treatment interaction (p= 0.035). ApoB (rs693) and LIPC (rs8034802) SNPs showed nominally significant associations with HDL-C and triglyceride changes with ILI and a treatment interaction (p<0.05). A PGS1 SNP (rs4082919) showed the most significant triglyceride treatment interaction in the full cohort (p=0.0009). Conclusions This is the first study to identify genetic variants modifying lipid responses to a randomized lifestyle behavior intervention in overweight/obese diabetic individuals. The effect of genetic factors on lipid changes may differ from the effects on baseline lipids and are modifiable by behavioral intervention. PMID:23861364

Influence of blood lipids on global coagulation test results.

PubMed

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon; Kim, Hyun Kyung

2015-01-01

High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

Influence of Blood Lipids on Global Coagulation Test Results

PubMed Central

Kim, Jung-Ah; Kim, Ji-Eun; Song, Sang Hoon

2015-01-01

Background High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). Methods PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). Results The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (≥200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (≥240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. Conclusion High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels. PMID:25553275

Role of Omega-3 Fatty Acids on Lipid Profile in Diabetic Dyslipidaemia: Single Blind, Randomised Clinical Trial.

PubMed

Chauhan, Shaylika; Kodali, Hanish; Noor, Jawad; Ramteke, Karuna; Gawai, Vidisha

2017-03-01

Diabetic dyslipidaemia is characterised by hypertriglyceridaemia, low High Density Lipoprotein (HDL), postprandial lipimea, small and dense LDL particles is considered to be a major predisposing factor for various macrovascular complications. Omega-3 fatty acids are fish oil derivative introduced in the market for dyslipidaemia associated with increased triglyceride level. To study the effect of omega-3 fatty acids on lipid profile in Type II diabetes patients. This study was prospective, single blind, randomized comparative trial. Hundred patients were randomized into three groups. Group I received metformin 500 mg twice daily and placebo, Group II received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) once daily and the Group III received metformin 500 mg twice daily and omega-3 fatty acids (1 gram) twice daily. ANOVA test was applied for analysis. Group II was effective in reducing the triglyceride level from 144.59±14.18 mg/dl to 101±13.31 mg/dl which was significant as compared to Group I from 147.67±18.57 mg/dl to 145.8±19.86 mg/dl respectively. Group III containing 1 g of omega-3 fatty acids twice daily showed decrease from 144.83±22.17 mg/dl to 86±17.46 mg/dl and was more effective in reducing triglyceride levels than Group II containing 1 gram of omega-3 fatty acids once daily. Omega-3 fatty acids can be given in conjunction with metformin to reduce triglyceride levels in diabetic dyslipidaemia without any adverse drug reactions or any drug interaction. Omega-3 fatty acids were effective in reducing the triglyceride level significantly as compared to placebo. Two grams of omega-3 fatty acids were more effective than 1 gram of omega-3 fatty acids in reducing triglyceride levels.

Relationship between insulin resistance-associated metabolic parameters and anthropometric measurements with sugar-sweetened beverage intake and physical activity levels in US adolescents: findings from the 1999-2004 National Health and Nutrition Examination Survey.

PubMed

Bremer, Andrew A; Auinger, Peggy; Byrd, Robert S

2009-04-01

To evaluate the relationship between insulin resistance-associated metabolic parameters and anthropometric measurements with sugar-sweetened beverage intake and physical activity levels. A cross-sectional analysis of the National Health and Nutrition Examination Survey data collected by the National Center for Health Statistics. Nationally representative samples of US adolescents participating in the National Health and Nutrition Examination Survey during the years 1999-2004. A total of 6967 adolescents aged 12 to 19 years. Sugar-sweetened beverage consumption and physical activity levels. Glucose and insulin concentrations, a homeostasis model assessment of insulin resistance (HOMA-IR), total, high-density lipoprotein, and low-density lipoprotein cholesterol concentrations, triglyceride concentrations, systolic and diastolic blood pressure, waist circumference, and body mass index (calculated as weight in kilograms divided by height in meters squared) percentile for age and sex. Multivariate linear regression analyses showed that increased sugar-sweetened beverage intake was independently associated with increased HOMA-IR, systolic blood pressure, waist circumference, and body mass index percentile for age and sex and decreased HDL cholesterol concentrations; alternatively, increased physical activity levels were independently associated with decreased HOMA-IR, low-density lipoprotein cholesterol concentrations, and triglyceride concentrations and increased high-density lipoprotein cholesterol concentrations. Furthermore, low sugar-sweetened beverage intake and high physical activity levels appear to modify each others' effects of decreasing HOMA-IR and triglyceride concentrations and increasing high-density lipoprotein cholesterol concentrations. Sugar-sweetened beverage intake and physical activity levels are each independently associated with insulin resistance-associated metabolic parameters and anthropometric measurements in adolescents. Moreover, low sugar-sweetened beverage intake and high physical activity levels appear to modify each others' effects on several health-related outcome variables.

Dietary medium-chain triglycerides attenuate hepatic lipid deposition in growing rats with protein malnutrition.

PubMed

Kuwahata, Masashi; Kubota, Hiroyo; Amano, Saki; Yokoyama, Meiko; Shimamura, Yasuhiro; Ito, Shunsuke; Ogawa, Aki; Kobayashi, Yukiko; Miyamoto, Ken-ichi; Kido, Yasuhiro

2011-01-01

The objective of this study was to investigate the effects of dietary medium-chain triglycerides (MCT) on hepatic lipid accumulation in growing rats with protein malnutrition. Weaning rats were fed either a low-protein diet (3%, LP) or control protein diet (20%, CP), in combination with or without MCT. The four groups were as follows: CP-MCT, CP+MCT, LP-MCT, and LP+MCT. Rats in the CP-MCT, CP+MCT and LP+MCT groups were pair-fed their respective diets based on the amount of diet consumed by the LP-MCT group. Rats were fed each experimental diet for 30 d. Four weeks later, the respiratory quotient was higher in the LP-MCT group than those in the other groups during the fasting period. Hepatic triglyceride content increased in the LP groups compared with the CP groups. Hepatic triglyceride content in the LP+MCT group, however, was significantly decreased compared with that in the LP-MCT group. Levels of carnitine palmitoyltransferase (CPT) 1a mRNA and CPT2 mRNA were significantly decreased in the livers of the LP-MCT group, as compared with corresponding mRNA levels of the other groups. These results suggest that ingestion of a low-protein diet caused fatty liver in growing rats. However, when rats were fed the low-protein diet with MCT, hepatic triglyceride deposition was attenuated, and mRNA levels encoding CPT1a and CPT2 were preserved at the levels of rats fed control protein diets.

[Characteristics of dyslipidemia in cancer patients].

PubMed

Ostroumova, M N; Kovalenko, I G; Bershteĭn, L M; Tsyrlina, E V; Dil'man, V M

1986-01-01

Blood concentrations of total cholesterol, cholesterol of very high density lipoproteins (alpha-cholesterol), triglycerides, beta-lipoproteins and 11-hydroxycorticosteroids were studied in 560 patients with rectal, colon, lung, ovarian, breast and endometrial cancer as well as in 238 controls. Patients with breast and rectal cancer were examined before and repeatedly after operation (every 6-12 months within 4-5 years). The blood concentration of total cholesterol was found to be elevated in breast cancer patients and controls with fibroadenomatosis and decreased in females with ovarian cancer and males with lung cancer. The level of blood alpha-cholesterol was decreased in males with all tumor localizations under study and in females with ovarian and rectal cancer. The concentration of triglycerides was increased in women patients only. Three possible causes of dyslipidemia in cancer patients are discussed: its development before tumor manifestation, the effect of tumor on the metabolic status of the host and the role of emotional stress in the increase of triglycerides level in the blood of primary cancer patients.

Aging affects the response of female rats to a hypercaloric diet.

PubMed

Arbo, B D; Niches, G; Zanini, P; Bassuino, D M; Driemeier, D; Ribeiro, M F; Cecconello, A L

2018-01-01

Metabolic syndrome is a major risk factor for the development of cardiovascular diseases and diabetes, among other conditions. Studies have shown that aging and metabolic syndrome share several metabolic alterations, and that aged individuals, in particular females, are at an increased risk of developing metabolic disorders. Although several studies have investigated the effects of hypercaloric diets in the development of obesity and metabolic syndrome in young animals, few studies have investigated these parameters in aged animals, especially in females. Therefore, the aim of this study was to investigate the effects of a hypercaloric diet in metabolic parameters of young and aged female rats, including its effects on lipid and glycemic profile and on liver lipid content. When compared to young animals, the aged rats presented increased serum levels of triglycerides and decreased serum levels of HDL cholesterol and glycemia, as well as increased hepatic levels of triglycerides and total cholesterol. The hypercaloric diet increased food intake, body weight gain and adiposity index, leading both young and aged animals to a dyslipidemia, represented by increased serum levels of triglycerides. The hypercaloric diet increased the glycemia and the HOMA index only in the young animals. On the other hand, the diet increased the frequency of hepatocellular microvacuolar degeneration only in the aged animals. In summary, it was observed that the females from different ages respond differently to hypercaloric diet intake: while the aged animals were more resistant to the changes in the glycemic profile, they were more susceptible to the hepatic damage caused by this diet. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes in triglyceride levels and risk for coronary heart disease in young men.

PubMed

Tirosh, Amir; Rudich, Assaf; Shochat, Tzippora; Tekes-Manova, Dorit; Israeli, Eran; Henkin, Yaakov; Kochba, Ilan; Shai, Iris

2007-09-18

Current triglyceride levels might be only a weak predictor of risk for coronary heart disease (CHD). To assess the association between changes over time in fasting triglyceride levels and CHD risk in young adults. Follow-up study over 5.5 years after 2 measurements of fasting triglycerides 5 years apart. The Staff Periodic Examination Center of the Israel Defense Forces, Zrifin, Israel. 13,953 apparently healthy, untreated, young men (age 26 to 45 years) with triglyceride levels less than 3.39 mmol/L (<300 mg/dL). Two triglyceride measurements (at enrollment [time 1] and 5 years later [time 2]), lifestyle variables, and incident cases of angiography-proven CHD. Within 5.5 years, 158 new cases of CHD were identified. The multivariate model was adjusted for age; family history; fasting glucose; high-density lipoprotein cholesterol; blood pressure; body mass index; and changes between time 1 and time 2 in body mass index, physical activity, smoking status, and habit of eating breakfast. Investigators categorized triglyceride levels according to low, intermediate, and high tertiles (as measured at time 1 and time 2 [expressed as tertile at time 1/tertile at time 2]). The risk for CHD in men with high-tertile triglyceride levels at time 1 changed depending on the tertile at time 2 (hazard ratios, 8.23 [95% CI, 2.50 to 27.13] for high/high, 6.84 [CI, 1.95 to 23.98] for high/intermediate, and 4.90 [CI, 1.01 to 24.55] for high/low, compared with the stable low/low group). The risk for CHD in men with low-tertile levels at time 1 also changed depending on the tertile at time 2 (hazard ratios, 3.81 [CI, 0.96 to 15.31] for low/intermediate and 6.76 [CI, 1.34 to 33.92] for low/high, compared with the stable low/low group). Participants were healthy and had a low incidence rate of CHD. The study was observational. Two triglyceride measurements obtained 5 years apart may assist in assessing CHD risk in young men. A decrease in initially elevated triglyceride levels is associated with a decrease in CHD risk compared with stable high triglyceride levels. However, this risk remains higher than in those with persistently low triglyceride levels.

Activation of ER stress and mTORC1 suppresses hepatic sortilin-1 levels in obese mice

PubMed Central

Ai, Ding; Baez, Juan M.; Jiang, Hongfeng; Conlon, Donna M.; Hernandez-Ono, Antonio; Frank-Kamenetsky, Maria; Milstein, Stuart; Fitzgerald, Kevin; Murphy, Andrew J.; Woo, Connie W.; Strong, Alanna; Ginsberg, Henry N.; Tabas, Ira; Rader, Daniel J.; Tall, Alan R.

2012-01-01

Recent GWAS have identified SNPs at a human chromosom1 locus associated with coronary artery disease risk and LDL cholesterol levels. The SNPs are also associated with altered expression of hepatic sortilin-1 (SORT1), which encodes a protein thought to be involved in apoB trafficking and degradation. Here, we investigated the regulation of Sort1 expression in mouse models of obesity. Sort1 expression was markedly repressed in both genetic (ob/ob) and high-fat diet models of obesity; restoration of hepatic sortilin-1 levels resulted in reduced triglyceride and apoB secretion. Mouse models of obesity also exhibit increased hepatic activity of mammalian target of rapamycin complex 1 (mTORC1) and ER stress, and we found that administration of the mTOR inhibitor rapamycin to ob/ob mice reduced ER stress and increased hepatic sortilin-1 levels. Conversely, genetically increased hepatic mTORC1 activity was associated with repressed Sort1 and increased apoB secretion. Treating WT mice with the ER stressor tunicamycin led to marked repression of hepatic sortilin-1 expression, while administration of the chemical chaperone PBA to ob/ob mice led to amelioration of ER stress, increased sortilin-1 expression, and reduced apoB and triglyceride secretion. Moreover, the ER stress target Atf3 acted at the SORT1 promoter region as a transcriptional repressor, whereas knockdown of Atf3 mRNA in ob/ob mice led to increased hepatic sortilin-1 levels and decreased apoB and triglyceride secretion. Thus, in mouse models of obesity, induction of mTORC1 and ER stress led to repression of hepatic Sort1 and increased VLDL secretion via Atf3. This pathway may contribute to dyslipidemia in metabolic disease. PMID:22466652

Plasma lipid levels predict dysglycemia in a biracial cohort of nondiabetic subjects: Potential mechanisms

PubMed Central

Owei, Ibiye; Umekwe, Nkiru; Wan, Jim

2016-01-01

Dyslipidemia and dysglycemia are etiologically associated, but the direction, chronology, and mechanisms of the association are not fully understood. We, therefore, analyzed data from 335 healthy adults (184 black, 151 white) enrolled in the Pathobiology of Prediabetes in A Biracial Cohort study. Subjects underwent oral glucose tolerance test (OGTT) and were enrolled if they had normal fasting and 2-h plasma glucose levels. Assessments during year 1 included anthropometry, fasting lipid profile, insulin sensitivity, and insulin secretion. Thereafter, OGTT was assessed annually for 5.5 years. The primary outcome was occurrence of prediabetes (impaired fasting glucose or impaired glucose tolerance) or diabetes. During a mean follow-up of 2.62 years, 110 participants (32.8%) developed prediabetes (N = 100) or diabetes (N = 10). In multivariate logistic regression models, higher baseline low-density lipoprotein (LDL) cholesterol and triglyceride levels and lower HDL cholesterol levels significantly increased the risk of incident prediabetes. The combined relative risk (95% confidence interval [CI]) of prediabetes for participants with lower baseline HDL cholesterol (10th vs. 90th percentile), higher LDL cholesterol (90th vs. 10th percentile) and high triglycerides levels (90th vs. 10th percentile) was 4.12 (95% CI 1.61–10.56), P = 0.0032. At baseline, lipid values showed significant associations with measures of adiposity, glycemia, insulin sensitivity, and secretion. In both ethnic groups, waist circumference correlated positively with triglycerides and inversely with HDL cholesterol levels (P = 0.0004–<0.0001); fasting plasma glucose correlated positively with triglycerides and LDL cholesterol levels and inversely with HDL cholesterol levels (P = 0.006–<0.0001); insulin sensitivity correlated positively with HDL cholesterol and inversely with triglyceride levels (P < 0.0001), and insulin secretion correlated positively with triglycerides (P = 0.01) and inversely with HDL cholesterol (P < 0.0001). We conclude that a baseline lipidemic signature identifies normoglycemic individuals at high risk for future glycemic progression, via congruent associations with adiposity and glucoregulatory mechanisms. These findings suggest that early lifestyle intervention could ameliorate progressive dyslipidemia and dysglycemia. PMID:27430991

Cardiovascular and Metabolic Effects of ANGPTL3 Antisense Oligonucleotides.

PubMed

Graham, Mark J; Lee, Richard G; Brandt, Teresa A; Tai, Li-Jung; Fu, Wuxia; Peralta, Raechel; Yu, Rosie; Hurh, Eunju; Paz, Erika; McEvoy, Bradley W; Baker, Brenda F; Pham, Nguyen C; Digenio, Andres; Hughes, Steven G; Geary, Richard S; Witztum, Joseph L; Crooke, Rosanne M; Tsimikas, Sotirios

2017-07-20

Epidemiologic and genomewide association studies have linked loss-of-function variants in ANGPTL3, encoding angiopoietin-like 3, with low levels of plasma lipoproteins. We evaluated antisense oligonucleotides (ASOs) targeting Angptl3 messenger RNA (mRNA) for effects on plasma lipid levels, triglyceride clearance, liver triglyceride content, insulin sensitivity, and atherosclerosis in mice. Subsequently, 44 human participants (with triglyceride levels of either 90 to 150 mg per deciliter [1.0 to 1.7 mmol per liter] or >150 mg per deciliter, depending on the dose group) were randomly assigned to receive subcutaneous injections of placebo or an antisense oligonucleotide targeting ANGPTL3 mRNA in a single dose (20, 40, or 80 mg) or multiple doses (10, 20, 40, or 60 mg per week for 6 weeks). The main end points were safety, side-effect profile, pharmacokinetic and pharmacodynamic measures, and changes in levels of lipids and lipoproteins. The treated mice had dose-dependent reductions in levels of hepatic Angptl3 mRNA, Angptl3 protein, triglycerides, and low-density lipoprotein (LDL) cholesterol, as well as reductions in liver triglyceride content and atherosclerosis progression and increases in insulin sensitivity. After 6 weeks of treatment, persons in the multiple-dose groups had reductions in levels of ANGPTL3 protein (reductions of 46.6 to 84.5% from baseline, P<0.01 for all doses vs. placebo) and in levels of triglycerides (reductions of 33.2 to 63.1%), LDL cholesterol (1.3 to 32.9%), very-low-density lipoprotein cholesterol (27.9 to 60.0%), non-high-density lipoprotein cholesterol (10.0 to 36.6%), apolipoprotein B (3.4 to 25.7%), and apolipoprotein C-III (18.9 to 58.8%). Three participants who received the antisense oligonucleotide and three who received placebo reported dizziness or headache. There were no serious adverse events. Oligonucleotides targeting mouse Angptl3 retarded the progression of atherosclerosis and reduced levels of atherogenic lipoproteins in mice. Use of the same strategy to target human ANGPTL3 reduced levels of atherogenic lipoproteins in humans. (Funded by Ionis Pharmaceuticals; ClinicalTrials.gov number, NCT02709850 .).

Short-term cooling increases serum triglycerides and small high-density lipoprotein levels in humans.

PubMed

Hoeke, Geerte; Nahon, Kimberly J; Bakker, Leontine E H; Norkauer, Sabine S C; Dinnes, Donna L M; Kockx, Maaike; Lichtenstein, Laeticia; Drettwan, Diana; Reifel-Miller, Anne; Coskun, Tamer; Pagel, Philipp; Romijn, Fred P H T M; Cobbaert, Christa M; Jazet, Ingrid M; Martinez, Laurent O; Kritharides, Leonard; Berbée, Jimmy F P; Boon, Mariëtte R; Rensen, Patrick C N

Cold exposure and β3-adrenergic receptor agonism, which both activate brown adipose tissue, markedly influence lipoprotein metabolism by enhancing lipoprotein lipase-mediated catabolism of triglyceride-rich lipoproteins and increasing plasma high-density lipoprotein (HDL) levels and functionality in mice. However, the effect of short-term cooling on human lipid and lipoprotein metabolism remained largely elusive. The objective was to assess the effect of short-term cooling on the serum lipoprotein profile and HDL functionality in men. Body mass index-matched young, lean men were exposed to a personalized cooling protocol for 2 hours. Before and after cooling, serum samples were collected for analysis of lipids and lipoprotein composition by 1 H-nuclear magnetic resonance. Adenosine triphosphate-binding cassette A1 (ABCA1)-mediated cholesterol efflux capacity of HDL was measured using [ 3 H]cholesterol-loaded ABCA1-transfected Chinese hamster ovary cells. Short-term cooling increased serum levels of free fatty acids, triglycerides, and cholesterol. Cooling increased the concentration of large very low-density lipoprotein (VLDL) particles accompanied by increased mean size of VLDL particles. In addition, cooling enhanced the concentration of small LDL and small HDL particles as well as the cholesterol levels within these particles. The increase in small HDL was accompanied by increased ABCA1-dependent cholesterol efflux in vitro. Our data show that short-term cooling increases the concentration of large VLDL particles and increases the generation of small LDL and HDL particles. We interpret that cooling increases VLDL production and turnover, which results in formation of surface remnants that form small HDL particles that attract cellular cholesterol. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

[Prevalence of metabolic syndrome in children with and without obesity].

PubMed

Guzmán-Guzmán, Iris Paola; Salgado-Bernabé, Aralia Berenice; Muñoz Valle, José Francisco; Vences-Velázquez, Amalia; Parra-Rojas, Isela

2015-03-09

Childhood obesity is considered the main risk factor for the development of metabolic syndrome (MetS) during childhood, adolescence and adulthood. This study aimed to determine the prevalence of MetS components and its main defining combinations in a sample of school children with and without obesity. A total of 225 children aged 6-12 years, 106 obese and 119 with normal weight were included. MetS was defined by the presence of 3 or more of the following: obesity as a body mass index ≥ 95th percentile, fasting glucose ≥ 100 mg/dL, triglycerides ≥ 150 mg/dL, high density lipoproteins cholesterol (HDL-c)<40 mg/dL and systolic and diastolic blood pressure ≥ 95th percentile. We found MetS components in both groups. Most frequent abnormalities in the obese group included increased levels of HDL-c, triglycerides, fasting glucose and total cholesterol, while increased levels of glucose and total cholesterol, and lower HDL-c levels predominated in the normal weight group. The prevalence of MetS in the obese group was 44.3% and, in normal weight children, it was 0.84%. The 3 main components that defined the MetS in the obese group were obesity/triglycerides/HDL-c (34.0%), obesity/glucose/triglycerides/HDL-c (29.8%) and obesity/glucose/HDL-c (14.9%), while the only combination observed in the normal weight group was glucose/HDL-c/triglycerides. A percentage of 44.3 of obese school children had MetS, and dyslipidemia showed to be strong determinants of MetS. Although the prevalence of MetS was low in children with normal weight, one third of them showed one of the components of MetS. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Effects of fructose consumption on food intake and biochemical and body parameters in Wistar rats.

PubMed

Ramos, Viviane Wagner; Batista, Leandro Oliveira; Albuquerque, Kelse Tibau

2017-12-01

Increased fructose consumption is associated with various metabolic changes that favor the onset of obesity and related comorbidities. The objective of this study was to assess the effects of chronic fructose consumption on body weight and adipose tissue, as well as on serum glucose and triglyceride levels. Thirty-day-old Wistar rats were divided into two groups: fructose (F) and control (C), which had free access to commercial chow and either water or a 20% fructose solution. Body mass was measured weekly and food consumption at 30, 60 and 90 days. At 90 days, the animals were killed by decapitation and fat deposits (mesenteric, epididymal and retroperitoneal) were removed and blood collected for measurement of glucose and triglyceride levels. There was no significant difference in body weight gain, but the percentage of body fat was higher in group F. This group also consumed less feed at 60 and 90 days and had higher consumption of fructose solution than water in group C at 30 and 60 days. This meant higher calorie intake in group F and lower feed efficiency. Retroperitoneal and epididymal fat deposits and triglycerides were higher in group F than in group C. Consumption of fructose solution for eight weeks, while not directly reflected in body weight gain, did increase abdominal fat in group F compared to group C, as well as changing triglyceride levels. These two factors increase risk of cardiovascular disease. Copyright © 2017 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

Hypofibrinolytic state in HIV-1-infected patients treated with protease inhibitor-containing highly active antiretroviral therapy.

PubMed

Koppel, Kristina; Bratt, Göran; Schulman, Sam; Bylund, Håkan; Sandström, Eric

2002-04-15

Decreased insulin sensitivity, hyperlipidemia, and body fat changes are considered as risk factors for coronary heart disease (CHD). A clustering of such factors (metabolic syndrome [MSDR]) exponentially increases the risk. Impaired fibrinolysis and increased coagulation are additional independent risk factors for CHD. We studied the effects of protease inhibitor (PI)-containing highly active antiretroviral therapy (HAART) on metabolic and hemostatic parameters in 363 HIV-infected individuals, of whom 266 were receiving PI-containing HAART and 97 were treatment naive. The fasting plasma levels of insulin, glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, plasminogen activator inhibitor type 1 (PAI-1), and fibrinogen were evaluated together with the areas of visceral adipose tissue and the visceral adipose tissue/subcutaneous adipose tissue area ratio. The levels of insulin, triglycerides, cholesterol, and low-density lipoprotein cholesterol; visceral adipose tissue area; low-density lipoprotein/high-density lipoprotein ratio; and visceral adipose tissue/subcutaneous adipose tissue area ratio were significantly increased in patients receiving PI-containing HAART compared with treatment-naive patients. The levels of PAI-1 and fibrinogen were significantly higher in patients receiving PI-containing HAART. PAI-1 levels were higher in individuals with MSDR but also in patients without MSDR who were receiving PI-containing HAART. PAI-1 was independently correlated to use of PI-containing HAART, triglyceride level, insulin level, and body mass index (p <.001). These findings suggest that patients receiving PI-containing HAART have decreased fibrinolysis and increased coagulability, which may thus represent additional risk factors for cardiovascular disease in this patient group.

Effect of increased magnesium intake on plasma cholesterol, triglyceride and oxidative stress in alloxan-diabetic rats.

PubMed

Olatunji, L A; Soladoye, A O

2007-06-01

Cardiovascular disorders are the primary causes of morbidity and mortality in patients with diabetes mellitus (DM). Agents that improve lipid profile and reduce oxidative stress have been shown to reduce the ensuing risk factors. In the present study, we investigated whether increased magnesium intake could improve hyperglycaemia, dyslipidaemia, and reduce oxidative stress in alloxan-induced diabetic rats. Male Wistar rats were divided into non-diabetic (ND), diabetic (DM) and diabetic fed on a high magnesium diet (DM-Mg) groups. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) were used as markers of oxidative stress. Plasma levels of ascorbic acid, magnesium and calcium were also determined. Diabetes was induced by injecting alloxan (100 mg/kg B.W). The fasting blood glucose levels were significantly lower in the DM-Mg rats than in the DM rats. Plasma total cholesterol, triglyceride, TBARS levels were significantly higher while plasma HDL-cholesterol, HDL-cholesterol/total cholesterol ratio, ascorbic acid levels were significantly lowered in DM rats compared with the ND rats. Increased intake of magnesium significantly abrogated these alterations. There were no significant differences in the plasma levels of magnesium and calcium between the DM and ND groups. However, plasma levels of magnesium but not calcium were significantly elevated in DM-Mg rats when compared with other groups. In conclusion, these results suggest that diet rich in magnesium could exert cardioprotective effect through reduced plasma total cholesterol, triglyceride, oxidative stress and ameliorated HDL-cholesterol/total cholesterol ratio as well as increased plasma ascorbic acid and magnesium in diabetic rats.

PCSK9 Induces CD36 Degradation and Affects Long-Chain Fatty Acid Uptake and Triglyceride Metabolism in Adipocytes and in Mouse Liver.

PubMed

Demers, Annie; Samami, Samaneh; Lauzier, Benjamin; Des Rosiers, Christine; Ngo Sock, Emilienne Tudor; Ong, Huy; Mayer, Gaetan

2015-12-01

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein receptor thereby elevating plasma low-density lipoprotein cholesterol levels and the risk of coronary heart disease. Thus, the use of PCSK9 inhibitors holds great promise to prevent heart disease. Previous work found that PCSK9 is involved in triglyceride metabolism, independently of its action on low-density lipoprotein receptor, and that other yet unidentified receptors could mediate this effect. Therefore, we assessed whether PCSK9 enhances the degradation of CD36, a major receptor involved in transport of long-chain fatty acids and triglyceride storage. Overexpressed or recombinant PCSK9 induced CD36 degradation in cell lines and primary adipocytes and reduced the uptake of the palmitate analog Bodipy FL C16 and oxidized low-density lipoprotein in 3T3-L1 adipocytes and hepatic HepG2 cells, respectively. Surface plasmon resonance, coimmunoprecipitation, confocal immunofluorescence microscopy, and protein degradation pathway inhibitors revealed that PCSK9 directly interacts with CD36 and targets the receptor to lysosomes through a mechanism involving the proteasome. Importantly, the level of CD36 protein was increased by >3-fold upon small interfering RNA knockdown of endogenous PCSK9 in hepatic cells and similarly increased in the liver and visceral adipose tissue of Pcsk9(-/-) mice. In Pcsk9(-/-) mice, increased hepatic CD36 was correlated with an amplified uptake of fatty acid and accumulation of triglycerides and lipid droplets. Our results demonstrate an important role of PCSK9 in modulating the function of CD36 and triglyceride metabolism. PCSK9-mediated CD36 degradation may serve to limit fatty acid uptake and triglyceride accumulation in tissues, such as the liver. © 2015 American Heart Association, Inc.

Relationship between circulating serum osteoprotegerin and total receptor activator of nuclear κ-B ligand levels, triglycerides, and coronary calcification in postmenopausal women.

PubMed

Poornima, Indu G; Mackey, Rachel H; Buhari, Alhaji M; Cauley, Jane A; Matthews, Karen A; Kuller, Lewis H

2014-07-01

This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.

Comparison of the pharmacological profiles of murine antisense oligonucleotides targeting apolipoprotein B and microsomal triglyceride transfer protein

PubMed Central

Lee, Richard G.; Fu, Wuxia; Graham, Mark J.; Mullick, Adam E.; Sipe, Donna; Gattis, Danielle; Bell, Thomas A.; Booten, Sheri; Crooke, Rosanne M.

2013-01-01

Therapeutic agents that suppress apolipoprotein B (apoB) and microsomal triglyceride transfer protein (MTP) levels/activity are being developed in the clinic to benefit patients who are unable to reach target LDL-C levels with maximally tolerated lipid-lowering drugs. To compare and contrast the metabolic consequences of reducing these targets, murine-specific apoB or MTP antisense oligonucleotides (ASOs) were administered to chow-fed and high fat-fed C57BL/6 or to chow-fed and Western diet-fed LDLr−/− mice for periods ranging from 2 to 12 weeks, and detailed analyses of various factors affecting fatty acid metabolism were performed. Administration of these drugs significantly reduced target hepatic mRNA and protein, leading to similar reductions in hepatic VLDL/triglyceride secretion. MTP ASO treatment consistently led to increases in hepatic triglyceride accumulation and biomarkers of hepatotoxicity relative to apoB ASO due in part to enhanced expression of peroxisome proliferator activated receptor γ target genes and the inability to reduce hepatic fatty acid synthesis. Thus, although both drugs effectively lowered LDL-C levels in mice, the apoB ASO produced a more positive liver safety profile. PMID:23220583

Rs964184 (APOA5-A4-C3-A1) is related to elevated plasma triglyceride levels, but not to an increased risk for vascular events in patients with clinically manifest vascular disease.

PubMed

van de Woestijne, Anton P; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Spiering, Wilko; Visseren, Frank L J

2014-01-01

Single nucleotide polymorphisms in the APOA5-A4-C3-A1 gene complex are associated with elevated plasma triglycerides and elevated vascular risk in healthy populations. In patients with clinically manifest vascular disease, hypertriglyceridemia and metabolic syndrome are frequently present, but the contribution of these single nucleotide polymorphisms to plasma triglycerides, effect modification by obesity and risk of recurrent vascular events is unknown in these patients. Prospective cohort study of 5547 patients with vascular disease. Rs964184 (APOA5-A4-C3-A1 gene complex) was genotyped, and we evaluated the relation with plasma lipid levels, presence of metabolic syndrome and the risk for new vascular events. The minor allele of rs964184 was strongly associated with log plasma triglycerides (β 0.12; 95%CI 0.10-0.15, p = 1.1*10(-19)), and was also associated with 0.03 mmol/L lower high-density lipoprotein-cholesterol (95%CI 0.01-0.04), and 0.14 mmol/L higher non-high-density lipoprotein-cholesterol (95%CI 0.09-0.20). The minor allele frequency increased from 10.9% in patients with plasma triglycerides <1 mmol/L to 24.6% in patients with plasma triglycerides between 4 and 10 mmol/L. The relation between rs964184 and plasma triglycerides was modified by body mass index in patients with one minor allele (β 0.02; (95%CI -0.04-0.09) if body mass index <24 kg/m2, β 0.17 (95%CI 0.12-0.22) if body mass index >27 kg/m2, p for interaction = 0.02). The prevalence of the metabolic syndrome increased from 52% for patients with two copies of the major allele to 62% for patients with two copies of the minor allele (p = 0.01). Rs964184 was not related with recurrent vascular events (HR 0.99; 95%CI 0.86-1.13). The single nucleotide polymorphism rs964184 (APOA5-A4-C3-A1) is associated with elevated plasma triglycerides concentrations in patients with clinically manifest vascular disease. In carriers of one minor allele, the effect on plasma triglycerides was modified by body mass index. There is no relation between rs964184 and recurrent vascular events in these patients.

Impact of a Water Intervention on Sugar-Sweetened Beverage Intake Substitution by Water: A Clinical Trial in Overweight and Obese Mexican Women.

PubMed

Hernández-Cordero, Sonia; Popkin, Barry M

2015-01-01

Intense marketing for sugar-sweetened beverages (SSB) along with the human innate preference for sweet taste contributes to the increase in consumption of SSB. It is important to understand the intricacies of dietary intake and global changes to the food supply to understand the complexities facing any intervention promoting water intake. We describe challenges to promote and achieve an increase in water intake and present key findings from a clinical trial examining the effects of substituting water for SSB on triglyceride levels, weight and other cardiometabolic factors in overweight/obese Mexican women. A randomized trial was conducted in Cuernavaca, Mexico selecting overweight/obese (BMI ≥25 and <39 kg/m(2)) women (18-45 years old), reporting an intake of SSB of at least 250 kcal/day. Women were randomly allocated to the water and education provision (WEP) group (n = 120) or to the education provision (EP) group (n = 120). Repeated 24 h dietary recall questionnaires, anthropometry, and fasting blood levels were collected at baseline and 3, 6, and 9 months following the intervention. There was no effect of the intervention on triglyceride concentration or on any of the studied outcomes. Post-hoc analyses according to weight at baseline show that triglyceride concentration decreased in obese women. Prevalence of metabolic syndrome after the intervention was lower in obese women from the WEP group. Water intake was increased but insufficient to achieve complete substitution of SSB, without effects on triglyceride concentration. Post-hoc analyses suggested that interventions lowered triglyceride concentration. Further studies are needed. © 2015 S. Karger AG, Basel.

Associations between Dietary Patterns, ADRβ2 Gln27Glu and ADRβ3 Trp64Arg with Regard to Serum Triglyceride Levels: J-MICC Study

PubMed Central

Nanri, Hinako; Nishida, Yuichiro; Nakamura, Kazuyo; Tanaka, Keitaro; Naito, Mariko; Yin, Guang; Hamajima, Nobuyuki; Takashima, Naoyuki; Suzuki, Sadao; Nindita, Yora; Kohno, Michiko; Uemura, Hirokazu; Koyama, Teruhide; Hosono, Satoyo; Mikami, Haruo; Kubo, Michiaki; Tanaka, Hideo

2016-01-01

Interactions between dietary patterns and 2 β-adrenergic receptor (ADRβ) gene polymorphisms (ADRβ2 Gln27Glu and ADRβ3 Trp64Arg) were examined with regard to the effects on serum triglyceride levels. The cross-sectional study comprised 1720 men and women (aged 35–69 years) enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study. Genotyping was conducted using a multiplex polymerase chain reaction-based invader assay. We used 46 items from a validated short food frequency questionnaire and examined major dietary patterns by factor analysis. We identified four dietary patterns: healthy, Western, seafood and bread patterns. There was no significant association between any dietary pattern and serum triglyceride levels. After a separate genotype-based analysis, significant interactions between ADRβ3 Trp64Arg genotype and the bread pattern (p for interaction = 0.01) were associated with serum triglyceride levels; specifically, after adjusting for confounding factors, Arg allele carriers with the bread pattern had lower serum triglycerides (p for trend = 0.01). However, the Trp/Trp homozygous subjects with the bread pattern showed no association with serum triglycerides (p for trend = 0.55). Interactions between other dietary patterns and ADRβ polymorphisms were not significant for serum triglyceride levels. Our findings suggest that ADRβ3 polymorphism modifies the effects of the bread pattern on triglyceride levels. PMID:27608039

Analysis of quantitative lipid traits in the genetics of NIDDM (GENNID) study.

PubMed

Malhotra, Alka; Wolford, Johanna K

2005-10-01

Coronary heart disease (CHD) is the leading cause of death among individuals with type 2 diabetes. Dyslipidemia contributes significantly to CHD in diabetic patients, in whom lipid abnormalities include hypertriglyceridemia, low HDL cholesterol, and increased levels of small, dense LDL particles. To identify genes for lipid-related traits, we performed genome-wide linkage analyses for levels of triglycerides and HDL, LDL, and total cholesterol in Caucasian, Hispanic, and African-American families from the Genetics of NIDDM (GENNID) study. Most lipid traits showed significant estimates of heritability (P < 0.001) with the exception of triglycerides and the triglyceride/HDL ratio in African Americans. Variance components analysis identified linkage on chromosome 3p12.1-3q13.31 for the triglyceride/HDL ratio (logarithm of odds [LOD] = 3.36) and triglyceride (LOD = 3.27) in Caucasian families. Statistically significant evidence for linkage was identified for the triglyceride/HDL ratio (LOD = 2.45) on 11p in Hispanic families in a region that showed suggestive evidence for linkage (LOD = 2.26) for triglycerides in this population. In African Americans, the strongest evidence for linkage (LOD = 2.26) was found on 19p13.2-19q13.42 for total cholesterol. Our findings provide strong support for previous reports of linkage for lipid-related traits, suggesting the presence of genes on 3p12.1-3q13.31, 11p15.4-11p11.3, and 19p13.2-19q13.42 that may influence traits underlying lipid abnormalities associated with type 2 diabetes.

Association of salivary triglycerides and cholesterol with dental caries in children with type 1 diabetes mellitus.

PubMed

Subramaniam, Priya; Sharma, Akhliesh; Kaje, Keerthan

2015-01-01

Metabolic disturbances in diabetes mellitus can affect oral health. Altered levels of salivary lipids have been suggested as a risk for dental caries. There has been lack of research in this regard and in children with type 1 diabetes mellitus. To assess the salivary triglycerides and cholesterol levels in children with type 1 diabetes mellitus and correlate them with their dental caries status. Thirty children aged 12-16 years with type 1 diabetes mellitus and 30 age- and gender-matched healthy children were included in the study. Unstimulated saliva was collected from each child and evaluated for salivary triglyceride and cholesterol levels. Dental caries status (DMFT) was recorded. Salivary cholesterol and triglyceride levels were significantly higher in children with type 1 diabetes mellitus (p ≤ 0.05). In comparison to controls, mean DMFT score was higher in the diabetic children. Salivary triglycerides showed a significant correlation with dental caries status in the study group (p = 0.035). In normal children, salivary cholesterol levels showed a significant association with dental caries. (p = 0.008). Both salivary cholesterol and triglycerides levels were significantly higher in children with type 1 diabetes mellitus. Salivary triglycerides showed a significant association with dental caries in these children. © 2014 Special Care Dentistry Association and Wiley Periodicals, Inc.

Prevalence of abnormal serum alanine aminotransferase levels in type 2 diabetic patients in Iran.

PubMed

Meybodi, M A; Afkhami-Ardekani, M; Rashidi, M

2008-09-15

This study was performed to estimate prevalence of transaminase levels in type 2 diabetic patients and identify contributing risk factors. In this cross-sectional study 348 patients with type 2 diabetes, who attended the diabetic clinic of Yazd Diabetes Research Center, were studied from October 2004 to December 2005. Patients with history of viral hepatitis, alcohol abuse and use of drug such as Amiodarone, Bleomycin, methotrexate, tamoxifen and sodium valporate was excluded. To examine the relationships between ALT, AST in individuals with type II diabetes and relation to various metabolic parameters like triglyceride, cholesterol, age, duration of diabetes, gender and BMI. Of 348 patients that entered the study, mean age was 58.8 +/- 11.5. Elevated ALT and AST were found in 10.4 and 3.3% of type 2 diabetic patients, respectively. Although the prevalence of elevated ALT increased with increasing age, FBS and triglyceride levels in subjects, but it was not statistically significant. There was a significant association between elevated ALT and gender as well as diabetes duration. The prevalence of elevated of ALT in type 2 diabetic patients is 1.6 times higher than general population in Iran unrelated to age, BMI, glycemic control, triglyceride levels. Identification risk factors and mechanisms of these elevations are very important and require further evaluation.

Optimal Fasting Time before Measurement of Serum Triglyceride Levels in Healthy Volunteers.

PubMed

Pongsuthana, Surapun; Tivatunsakul, Naris

2016-02-01

Coronary heart disease is a major public health problem. Elevated triglyceride levels are a risk factor for atherosclerosis and coronary heart disease. Food intake interferes with the measurement of serum triglyceride levels, and in previous studies, fasting for 12 hours was recommended before blood sampling. In real-world practice, long fasting times cause patient discomfort and poor compliance, and the present study was, therefore, designed to determine the appropriate fasting time prior to measuring serum triglyceride levels. To determine the appropriate fasting time before measuring serum triglyceride levels. This was a pilot study performed using healthy volunteers aged between 20 and 30 years old from November 2013 to December 2013 at Rajavithi Hospital. The first blood sample was measured in the morning after fasting over 12 hours. The subjects then took their regular breakfast, after which they fasted for 8 hours. Blood samples were taken 6 and 8 hours later and sent to the laboratory for measurement of serum triglyceride levels. 40 volunteers, of whom 25 were female, were enrolled. Their mean age was 25.9 ± 2.81 years old, and their mean weight, height, and body mass index were 61.5 ± 12.5 kg, 167.2 ± 8.3 cm and 21.84 ± 3.1 kg/m2, respectively. Mean fasting serum triglyceride level at 12 hours was 80.23 ± 36.33 mg/dl, at 6 hours it was 110.65 ± 73.45 mg/dl, and at 8 hours it was 75.62 ± 46.81 mg/dl. The group fasting for 12 hours had significantly lower serum triglyceride levels than the group fasting for 6 hours (p-value = 0.003), but no significant difference was found between the group fasting for 12 hours and the one fasting for 8 hours (p-value = 0.493). The present study showed no significant difference in triglyceride levels in patients who had fasted or 8 hours and those who had done so for 12 hours. Fasting for only 8 hours before measurement of serum triglyceride may be sufficient.

Triglycerides and Heart Disease, Still a Hypothesis?

PubMed Central

Goldberg, Ira J.; Eckel, Robert H.; McPherson, Ruth

2011-01-01

The purpose of this article is to review the basic and clinical science relating plasma triglycerides and cardiovascular disease. Although many aspects of the basic physiology of triglyceride production, its plasma transport and tissue uptake have been known for several decades, the relationship of plasma triglyceride levels to vascular disease is uncertain. Are triglyceride rich lipoproteins, their influence on HDL and LDL, or the underlying diseases leading to defects in triglyceride metabolism the culprit? Animal models have failed to confirm that anything other than early fatty lesions can be produced by triglyceride-rich lipoproteins. Metabolic products of triglyceride metabolism can be toxic to arterial cells; however, these studies are primarily in vitro. Correlative studies of fasting and postprandial triglycerides and genetic diseases implicate VLDL and their remnants, and chylomicron remnants in atherosclerosis development; but the concomitant alterations in other lipoproteins and other risk factors obscure any conclusions about direct relationships between disease and triglycerides. Genes that regulate triglyceride levels also correlate with vascular disease. Human intervention trials, however, have lacked an appropriately defined population, and have produced outcomes without definitive conclusions. The time is more than ripe for new and creative approaches to understanding the relationship of triglycerides and heart disease. PMID:21527746

Atypical antipsychotic medications increase postprandial triglyceride and glucose levels in male rats: relationship with stearoyl-CoA desaturase activity.

PubMed

McNamara, Robert K; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W

2011-06-01

Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 (Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, and 6mg/kg/d), paliperidone (1.5, 3, and 6mg/kg/d), olanzapine (2.5, 5, and 10mg/kg/d), quetiapine (5, 10, and 20mg/kg/d), haloperidol (1, and 3mg/kg/d) or vehicle through their drinking water for 40days. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, 'desaturation index') were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n=122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG and glucose levels, and that concomitant elevations in PUFA biosynthesis oppose these effects. Copyright © 2011 Elsevier B.V. All rights reserved.

Atypical Antipsychotic Medications Increase Postprandial Triglyceride and Glucose Levels in Male Rats: Relationship with Stearoyl-CoA Desaturase Activity

PubMed Central

McNamara, Robert K.; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Cole-Strauss, Allyson; Lipton, Jack W.

2011-01-01

Recent preclinical and clinical evidence suggests that the stearoyl-CoA desaturase-1 (Scd1) enzyme plays a key role in the regulation of triglyceride (TG) biosynthesis and insulin sensitivity, and in vitro studies have found that antipsychotic medications up-regulate Scd1 mRNA expression. To investigate these effects in vivo, rats were treated with risperidone (1.5, 3, 6 mg/kg/d), paliperidone (1.5, 3, 6 mg/kg/d), olanzapine (2.5, 5, 10 mg/kg/d), quetiapine (5, 10, 20 mg/kg/d), haloperidol (1, 3 mg/kg/d) or vehicle through their drinking water for 40 d. Effects on liver Scd1 mRNA expression and an index of Scd1 activity (the plasma 18:1/18:0 ratio, ‘deaturation index’) were determined, as were postprandial plasma triglyceride (TG), glucose, insulin, and polyunsaturated fatty acid (PUFA) levels. All atypical antipsychotics increased the plasma 18:1/18:0 ratio, but not liver Scd1 mRNA expression, at doses found to also increase plasma TG levels. Among all rats (n=122), the plasma 18:1/18:0 ratio accounted for 56% of the variance in TG concentrations. The plasma 18:1/18:0 ratio was also positively associated with erythrocyte and heart membrane phospholipid 18:1n-9 composition. All antipsychotics except risperidone increased glucose levels at specific doses, and none of the antipsychotics significantly altered insulin levels. The plasma 18:1/18:0 ratio accounted for 20% of the variance in glucose levels. Plasma omega-3 and omega-6 PUFA levels were inversely correlated with the plasma 18:1/18:0 ratio and TG and glucose levels. These in vivo data demonstrate that different atypical antipsychotic medications increase the plasma 18:1/18:0 ratio in association with elevations in postprandial TG levels, and that concomitant elevations in PUFA biosynthesis oppose these effects. PMID:21474290

Sasang constitutional types for the risk prediction of metabolic syndrome: a 14-year longitudinal prospective cohort study.

PubMed

Lee, Sunghee; Lee, Seung Ku; Kim, Jong Yeol; Cho, Namhan; Shin, Chol

2017-09-02

To examine whether the use of Sasang constitutional (SC) types, such as Tae-yang (TY), Tae-eum (TE), So-yang (SY), and So-eum (SE) types, increases the accuracy of risk prediction for metabolic syndrome. From 2001 to 2014, 3529 individuals aged 40 to 69 years participated in a longitudinal prospective cohort. The Cox proportional hazard model was utilized to predict the risk of developing metabolic syndrome. During the 14 year follow-up, 1591 incident events of metabolic syndrome were observed. Individuals with TE type had higher body mass indexes and waist circumferences than individuals with SY and SE types. The risk of developing metabolic syndrome was the highest among individuals with the TE type, followed by the SY type and the SE type. When the prediction risk models for incident metabolic syndrome were compared, the area under the curve for the model using SC types was significantly increased to 0.8173. Significant predictors for incident metabolic syndrome were different according to the SC types. For individuals with the TE type, the significant predictors were age, sex, body mass index (BMI), education, smoking, drinking, fasting glucose level, high-density lipoprotein (HDL) cholesterol level, systolic and diastolic blood pressure, and triglyceride level. For Individuals with the SE type, the predictors were sex, smoking, fasting glucose, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level, while the predictors in individuals with the SY type were age, sex, BMI, smoking, drinking, total cholesterol level, fasting glucose level, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level. In this prospective cohort study among 3529 individuals, we observed that utilizing the SC types significantly increased the accuracy of the risk prediction for the development of metabolic syndrome.

Allelic variation in ApoC3, ApoA5 and LPL genes and first and second generation antipsychotic effects on serum lipids in patients with schizophrenia.

PubMed

Smith, R C; Segman, R H; Golcer-Dubner, T; Pavlov, V; Lerer, B

2008-06-01

Schizophrenic patients who are treated with antipsychotics, especially second generation antipsychotics, such as clozapine and olanzapine, manifest an increase in cholesterol and triglycerides as well as other changes associated with diabetes or the metabolic syndrome. Previous studies have shown that polymorphisms in several genes that regulate lipid metabolism can influence the levels of these lipids and response to drug treatment. We have investigated in an exploratory study whether polymorphisms in the apolipoprotein C-III (ApoC3), apolipoprotein A-V gene (ApoA5) and lipoprotein lipase genes influence differential lipid response to treatment with three second generation antipsychotics-olanzapine, clozapine and risperidone-or treatment with a first generation antipsychotic. A total of 189 patients with schizophrenia or schizoaffective disorder who were being treated with a single antipsychotic were studied in a cross-sectional study design in which fasting serum cholesterol and triglycerides and selected single-nucleotide polymorphosms (SNPs) in the three lipid metabolism genes were assessed. The treatment with antipsychotic monotherapy makes drug haplotype ascertainment less complex. Our analyses showed several nominally significant drug x gene and drug x haplotype interactions. The rarer C allele or the ApoA5_1131 (T/C) SNP was associated with higher cholesterol levels in patients treated with first generation antipsychotics and lower cholesterol levels in patients treated with olanzapine or clozapine. The rarer C allele of the ApoA5_SW19 (G/C) SNP was associated with higher cholesterol in risperidone-treated patients. An ApoA5 CG haplotype was associated with decreased cholesterol in olanzapine- or clozapine-treated patients and higher cholesterol in patients treated with first generation antipsychotics. The presence of the rarer T allele of the ApoC3_1100 (C/T) SNP or the presence of the ApoC3 TG haplotype was associated with decreased triglyceride levels in patients treated with olanzapine or clozapine and a nonsignificant trend for increased triglycerides in patients treated with first generation antipsychotics. The presence of the ApoC3 CC haplotype was associated with increased triglycerides in patients treated with olanzapine or clozapine. The overall magnitude of the effects was not large. These results provide a potential initial step toward a pharmacogenetic approach to selection of antipsychotic treatment which may help minimize the side effect of increases in serum lipids.

Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries.

PubMed

Sacks, Frank M; Hermans, Michel P; Fioretto, Paola; Valensi, Paul; Davis, Timothy; Horton, Edward; Wanner, Christoph; Al-Rubeaan, Khalid; Aronson, Ronnie; Barzon, Isabella; Bishop, Louise; Bonora, Enzo; Bunnag, Pongamorn; Chuang, Lee-Ming; Deerochanawong, Chaicharn; Goldenberg, Ronald; Harshfield, Benjamin; Hernández, Cristina; Herzlinger-Botein, Susan; Itoh, Hiroshi; Jia, Weiping; Jiang, Yi-Der; Kadowaki, Takashi; Laranjo, Nancy; Leiter, Lawrence; Miwa, Takashi; Odawara, Masato; Ohashi, Ken; Ohno, Atsushi; Pan, Changyu; Pan, Jiemin; Pedro-Botet, Juan; Reiner, Zeljko; Rotella, Carlo Maria; Simo, Rafael; Tanaka, Masami; Tedeschi-Reiner, Eugenia; Twum-Barima, David; Zoppini, Giacomo; Carey, Vincent J

2014-03-04

Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Rapid quantification of neutral lipids and triglycerides during zebrafish embryogenesis.

PubMed

Yoganantharjah, Prusothman; Byreddy, Avinesh R; Fraher, Daniel; Puri, Munish; Gibert, Yann

2017-01-01

The zebrafish is a useful vertebrate model to study lipid metabolism. Oil Red-O (ORO) staining of zebrafish embryos, though sufficient for visualizing the localization of triglycerides, was previously inadequate to quantify neutral lipid abundance. For metabolic studies, it is crucial to be able to quantify lipids during embryogenesis. Currently no cost effective, rapid and reliable method exists to quantify the deposition of neutral lipids and triglycerides. Thin layer chromatography (TLC), gas chromatography and mass spectrometry can be used to accurately measure lipid levels, but are time consuming and costly in their use. Hence, we developed a rapid and reliable method to quantify neutral lipids and triglycerides. Zebrafish embryos were exposed to Rimonabant (Rimo) or WIN 55,212-2 mesylate (WIN), compounds previously shown to modify lipid content during zebrafish embryogenesis. Following this, ORO stain was extracted out of both the zebrafish body and yolk sac and optical density was measured to give an indication of neutral lipid and triglyceride accumulation. Embryos treated with 0.3 microM WIN resulted in increased lipid accumulation, whereas 3 microM Rimo caused a decrease in lipid accumulation during embryogenesis. TLC was performed on zebrafish bodies to validate the developed method. In addition, BODIPY free fatty acids were injected into zebrafish embryos to confirm quantification of changes in lipid content in the embryo. Previously, ORO was limited to qualitative assessment; now ORO can be used as a quantitative tool to directly determine changes in the levels of neutral lipids and triglycerides.

Work-family spillover and metabolic syndrome indicators: Findings from a national sample.

PubMed

Versey, H Shellae; Tan, Mingxuan

2018-03-01

This study examines the link between negative work-family spillover and metabolic risk factors over a 9-year period. Data from two waves of the Midlife in the United States Survey were used to explore relationships between negative work-family spillover and four indicators of metabolic syndrome-blood pressure, triglycerides, body mass index, and glucose levels. In a sample of full-time working men and women ( N = 630), increased negative spillover at baseline significantly predicted higher body mass index nearly a decade later, with a marginally significant effect for triglyceride levels. Increases in spillover also body mass index and glucose levels at follow-up. This study extends research tying work-life spillover to health and suggests that further investigation is needed to fully understand the long-term effects of work stress.

The effects of coffee consumption on serum lipids and lipoprotein in healthy individuals.

PubMed

Onuegbu, A J; Agbedana, E O

2001-01-01

The changes in total serum cholestrol, serum triglyceride, HDL-cholesterol and LDL-cholesterol after twenty eight (28) days of consumption of moderate quantity of a commercial coffee preparation (NESCAFE brand) were studied in 30 human subjects consisting of 20 male and 10 female healthy adults. Significant increases in the mean total serum cholesterol concentration (110.8-126.5 mg/100 mls) and LDL- cholesterol concentration (78.4-94.5 mg/100 ml) were observed in the subjects. No significant differences were obtained in the mean HDL cholesterol concentration and in the mean serum triglyceride levels. The differences observed in the mean total serum cholesterol, LDL cholesterol, HDL- cholesterol and triglyceride concentrations in the individual male and female groups studied were not statistically significant. The results from this study suggest that short-term consumption of coffee may increase the total serum cholesterol and LDL cholesterol levels. It is therefore possible that long-term consumption of coffee may lead to clinically significant alterations in serum lipid profile and could be important in the aetiology of atherosclerotic vascular diseases such as coronary heart disease.

In Vivo Characterization of Human APOA5 Haplotypes

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

Ahituv, Nadav; Akiyama, Jennifer; Chapman-Helleboid, Audrey

2006-10-01

Increased plasma triglycerides concentrations are an independent risk factor for cardiovascular disease. Numerous studies support a reproducible genetic association between two minor haplotypes in the human apolipoprotein A5 gene (APOA5) and increased plasma triglyceride concentrations. We thus sought to investigate the effect of these minor haplotypes (APOA5*2 and APOA5*3) on ApoAV plasma levels through the precise insertion of single-copy intact APOA5 haplotypes at a targeted location in the mouse genome. While we found no difference in the amount of human plasma ApoAV in mice containing the common APOA5*1 and minor APOA5*2 haplotype, the introduction of the single APOA5*3 defining allelemore » (19W) resulted in 3-fold lower ApoAV plasma levels consistent with existing genetic association studies. These results indicate that S19W polymorphism is likely to be functional and explain the strong association of this variant with plasma triglycerides supporting the value of sensitive in vivo assays to define the functional nature of human haplotypes.« less

Delayed clearance of triglyceride‐rich lipoproteins in young, healthy obese subjects†

PubMed Central

Goll, R.; Lekahl, S.; Moen, O. S.; Florholmen, J.

2015-01-01

Summary Obesity is associated with the metabolic syndrome. The aims were, first, to study the postprandial triglyceride clearance in young, healthy obese subjects and, second, to investigate if fasting triglycerides can predict delayed postprandial triglyceride clearance. Eighteen apparently healthy, obese subjects with no clinical signs of metabolic disturbances participated. Controls were age‐ and sex‐matched, healthy, normal weight subjects. Subclinical markers of metabolic disturbances were assessed by measuring postprandial triglycerides in serum and in chylomicrons by oral fat tolerance test. Postprandial triglyceride clearance for 8 h was assessed indirectly as removal of the lipid from serum during the oral fat tolerance test. Insulin resistance was measured by the homeostasis model assessment of insulin resistance (HOMA‐IR). Twelve (66%) of the apparently healthy obese individuals had insulin resistance measured by HOMA‐IR. There was a delayed clearance of serum triglycerides and chylomicron triglycerides at 6 h when compared with the control group, while, at 8 h, the differences were only detected for the chylomicron triglyceride clearance. Triglyceride response was significantly greater in the obese subjects. Fasting triglycerides in upper normal level predicted a delayed postprandial triglyceride clearance and insulin resistance. In young, apparently healthy obese subjects early metabolic disturbances including insulin resistance and delayed postprandial triglyceride clearance can be detected. Fasting serum triglyceride in upper normal level predicted delayed postprandial triglyceride clearance and insulin resistance. PMID:26469529

Betaine supplement alleviates hepatic triglyceride accumulation of apolipoprotein E deficient mice via reducing methylation of peroxisomal proliferator-activated receptor alpha promoter

PubMed Central

2013-01-01

Background Betaine is a methyl donor and has been considered as a lipotropic effect substance. But its mechanism remains unclear. Hepatic steatosis is associated with abnormal expression of genes involved in hepatic lipid metabolism. DNA methylation contributes to the disregulation of gene expression. Here we hypothesized that betaine supplement and subsequent DNA methylation modifications alter the expression of genes that are involved in hepatic lipid metabolism and hence alleviate hepatic triglyceride accumulation. Methods Male wild-type (WT) C57BL/6 mice (n = 6) were fed with the AIN-93 G diet. ApoE−/− mice (n = 12), weight-matched with the WT mice, were divided into two groups (n = 6 per group), and fed with the AIN-93 G diet and AIN-93 G supplemented with 2% betaine/100 g diet. Seven weeks after the intervention, mice were sacrificed. Liver betaine, choline, homocysteine concentration were measured by HPLC. Liver oxidants activity and triglyceride level were assessed by ultraviolet spectrophotometry. Finally, hepatic PPAR alpha gene and its target genes expression levels and the methylation status of the PPAR alpha gene were determined. Results ApoE−/− mice had higher hepatic triglyceride and lower GSH-Px activity when compared with the WT mice. Betaine intervention reversed triglyceride deposit, enhanced SOD and GSH-Px activity in the liver. Interestingly, mice fed on betaine-supplemented diet showed a dramatic increase of hepatic choline concentration and a decrease of betaine and homocysteine concentration relative to the WT mice and the ApoE−/− mice absent with betaine intervention. Expression of PPAR alpha and CPT1 were decreased and expression of FAS was markedly increased in ApoE−/− mice. In parallel, PPAR alpha promoter methylation level were slightly increased in ApoE−/− mice though without significance. Betaine supplement upregulated expression of PPAR alpha and its target genes (CPT1, CYP2E1) and reversed hypermethylation of PPAR alpha promoter of ApoE−/− mice. Furthermore, PPAR alpha methylation was positively correlated with hepatic betaine concentration. Conclusions Our findings indicate that betaine supplement could alleviate hepatic triglyceride accumulation and improve antioxidant capacity by decreasing PPAR alpha promoter methylation and upregulating PPAR alpha and its target genes mRNA expression. PMID:23497035

Parenteral structured triglyceride emulsion improves nitrogen balance and is cleared faster from the blood in moderately catabolic patients.

PubMed

Kruimel, J W; Naber, T H; van der Vliet, J A; Carneheim, C; Katan, M B; Jansen, J B

2001-01-01

Most postoperative patients lose net protein mass, which reflects loss of muscle tissue and organ function. Perioperative parenteral nutrition may reduce the loss of protein, but in general, with conventional lipid emulsions a waste of protein still remains. We compared the effects on nitrogen balance of an emulsion containing structured triglycerides, a new type of synthesized triglycerides, with an emulsion of a physical mixture of medium- and long-chain triglycerides as part of parenteral feeding in moderately catabolic patients. The first 5 days after placement of an aortic prosthesis patients received total parenteral nutrition (TPN) providing 0.2 g of nitrogen per kg body weight per day; energy requirement was calculated using Harris and Benedict's equation, adding 300 kcal per day for activity. Twelve patients were treated with the structured triglyceride emulsion and 13 patients with the emulsion of the physical mixture of medium- and long-chain triglycerides. The design was a randomized, double-blind parallel study. In the patients who completed the study, the mean cumulative nitrogen balance over the first 5 postoperative days was -8+/-2 g in 10 patients on the structured triglyceride emulsion and -21+/-4 g in 9 patients on the emulsion of the physical mixture of medium- and long-chain triglycerides; the mean difference was 13 g of nitrogen (95% confidence interval 4 to 22, p = .015) in favor of the structured triglyceride emulsion. On the first postoperative day serum triglyceride and plasma medium-chain free fatty acid levels increased less during infusion of the structured triglyceride emulsion than with the physical mixture emulsion. The parenteral structured triglyceride emulsion improves the nitrogen balance and is cleared faster from the blood, compared with the emulsion of the physical mixture of medium- and long-chain triglycerides, in moderately catabolic patients.

Cardiac Expression of Microsomal Triglyceride Transfer Protein Is Increased in Obesity and Serves to Attenuate Cardiac Triglyceride Accumulation

PubMed Central

Bartels, Emil D.; Nielsen, Jan M.; Hellgren, Lars I.; Ploug, Thorkil; Nielsen, Lars B.

2009-01-01

Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease. PMID:19390571

Salacia oblonga root improves postprandial hyperlipidemia and hepatic steatosis in Zucker diabetic fatty rats: Activation of PPAR-{alpha}

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

Hsun-Wei Huang, Tom; Peng Gang; Qian Li, George

Salacia oblonga (SO) root is an Ayurvedic medicine with anti-diabetic and anti-obese properties. Peroxisome proliferator-activated receptor (PPAR)-{alpha}, a nuclear receptor, plays an important role in maintaining the homeostasis of lipid metabolism. Here, we demonstrate that chronic oral administration of the water extract from the root of SO to Zucker diabetic fatty (ZDF) rats, a genetic model of type 2 diabetes and obesity, lowered plasma triglyceride and total cholesterol (TC) levels, increased plasma high-density lipoprotein levels and reduced the liver contents of triglyceride, non-esterified fatty acids (NEFA) and the ratio of fatty droplets to total tissue. By contrast, the extract hadmore » no effect on plasma triglyceride and TC levels in fasted ZDF rats. After olive oil administration to ZDF the extract also inhibited the increase in plasma triglyceride levels. These results suggest that SO extract improves postprandial hyperlipidemia and hepatic steatosis in ZDF rats. Additionally, SO treatment enhanced hepatic expression of PPAR-{alpha} mRNA and protein, and carnitine palmitoyltransferase-1 and acyl-CoA oxidase mRNAs in ZDF rats. In vitro, SO extract and its main component mangiferin activated PPAR-{alpha} luciferase activity in human embryonic kidney 293 cells and lipoprotein lipase mRNA expression and enzyme activity in THP-1 differentiated macrophages; these effects were completely suppressed by a selective PPAR-{alpha} antagonist MK-886. The findings from both in vivo and in vitro suggest that SO extract functions as a PPAR-{alpha} activator, providing a potential mechanism for improvement of postprandial hyperlipidemia and hepatic steatosis in diabetes and obesity.« less

[Effect of healthy diet and physical activity on the level of non-HDL cholesterol in obese subjects without cardiovascular disease and diabetes mellitus].

PubMed

Móczár, Csaba

2015-10-18

Prevention program including lifestyle changes was initiated with the participation of obese and overweight subjects recruited from the practices of 29 family doctors. The aim of the author was to analyse changes of non-HDL-cholesterol levels, especially when triglyceride levels were above 2.26 mmol/l, and when non-HDL cholesterol levels were high in association with low HDL-cholesterol levels in overweight or obese subjects who had no cardiovascular disease and diabetes mellitus. Data obtained from 1192 subjects (424 men and 768 women) before and 12 month after inclusion into the prevention program was analysed. The average level of non-HDL-cholesterol in the whole group of subjects decreased from 4.74 to 4.64 mmol/l, but the change was not significant. However, the average concentration of non-HDL-cholesterol was reduced significantly from 4.87 to 4.4 mmol/l in men, whereas no significant change was detected in women. In cases when triglyceride levels were higher than 2.26 mmol/l, the non-HDL-cholesterol level was reduced by 0.65 mmol/l. In cases when the non-HDL-cholesterol level was high in association with low HDL-cholesterol level, the non-HDL-cholesterol was significantly decreased from 5.22 to 4.48 mmol/l. In addition, in cases when HDL-cholesterol levels were low, the average level of the HDL-cholesterol significantly increased from 0.84 to 1.3 mmol/l. Lifestyle changes decrease the level of atherogenic lipid fractions, particularly in men with high triglyceride levels. Improvement of the atherogenic lipid profile in response to lifestyle changes is related not only to the reduction of atherogenic lipid fractions, but also to the increase of HDL-cholesterol level.

Triglyceride-Lowering Effects of Two Probiotics, Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601, in a Rat Model of High-Fat Diet-Induced Hypertriglyceridemia.

PubMed

Choi, Il-Dong; Kim, Sung-Hwan; Jeong, Ji-Woong; Lee, Dong Eun; Huh, Chul-Sung; Hong, Seong Soo; Sim, Jae-Hun; Ahn, Young-Tae

2016-03-01

The triglyceride-lowering effect of probiotics Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 were investigated. Male SD Wistar rats were randomly divided into three groups and fed high-fat diet (HFD), HFD and probiotics (5 X 10(9) CFU/day of L. plantarum KY1032 and 5 X 10(9) CFU/day of L. curvatus HY7601), or normal diet for 6 weeks. Probiotic treatment significantly lowered the elevated plasma triglyceride and increased plasma free fatty acid, glycerol, and plasma apolipoprotein A-V (ApoA-V) levels. The probiotic-treated group showed elevated hepatic mRNA expression of PPARα, bile acid receptor (FXR), and ApoA-V. These results demonstrate that L. plantarum KY1032 and L. curvatus HY7601 lower triglycerides in hypertriglyceridemic rats by upregulating ApoA-V, PPARα, and FXR.

Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones

PubMed Central

Chao, Lily; Marcus-Samuels, Bernice; Mason, Mark M.; Moitra, Jaideep; Vinson, Charles; Arioglu, Elif; Gavrilova, Oksana; Reitman, Marc L.

2000-01-01

There is uncertainty about the site(s) of action of the antidiabetic thiazolidinediones (TZDs). These drugs are agonist ligands of the transcription factor PPARγ, which is abundant in adipose tissue but is normally present at very low levels in liver and muscle. We have studied the effects of TZDs in A-ZIP/F-1 mice, which lack white adipose tissue. The A-ZIP/F-1 phenotype strikingly resembles that of humans with severe lipoatrophic diabetes, including the lack of fat, marked insulin resistance and hyperglycemia, hyperlipidemia, and fatty liver. Rosiglitazone or troglitazone treatment did not reduce glucose or insulin levels, suggesting that white adipose tissue is required for the antidiabetic effects of TZDs. However, TZD treatment was effective in lowering circulating triglycerides and increasing whole body fatty acid oxidation in the A-ZIP/F-1 mice, indicating that this effect occurs via targets other than white adipose tissue. A-ZIP/F-1 mice have markedly increased liver PPARγ mRNA levels, which may be a general property of fatty livers. Rosiglitazone treatment increased the triglyceride content of the steatotic livers of A-ZIP/F-1 and ob/ob mice, but not the “lean” livers of fat-transplanted A-ZIP/F-1 mice. In light of this evidence that rosiglitazone acts differently in steatotic livers, the effects of rosiglitazone, particularly on hepatic triglyceride levels, should be examined in humans with hepatic steatosis. PMID:11086023

Effects of castration on expression of lipid metabolism genes in the liver of korean cattle.

PubMed

Baik, Myunggi; Nguyen, Trang Hoa; Jeong, Jin Young; Piao, Min Yu; Kang, Hyeok Joong

2015-01-01

Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.

Effects of soybean lipid infusion on triglyceride and unbound free fatty acid levels in preterm infants.

PubMed

Hegyi, Thomas; Kleinfeld, Alan; Huber, Andrew; Weinberger, Barry; Memon, Naureen; Joe Shih, Weichung; Carayannopoulos, Mary; Oh, William

2018-04-18

To determine the plasma triglyceride (TG) and unbound free fatty acid (FFAu) levels in infants treated with increasing dosages of soybean lipid, intralipid (IL), infusion. TG and FFAu levels were measured in 78 preterm infants (BW 500-2000 g; GA 23-34 weeks) using the fluorescent probe ADIFAB2 and enzymatic method. The infants' BW was 1266.2 ± 440.7 g and GA 28.8 ± 3.1 weeks. TG levels were 77.4 ± 50 mg/dL, 140.2 ± 188 mg/dL (p < .04 compared to levels during low dose IL infusion) and 135.6 ± 118 mg/dL (p < .004), respectively during increased IL rates. FFAu levels were 17.7 ± 13 nM, 47.3 ± 102.8 nM (p = .07) and 98 ± 234 nM (p = .03). TG levels correlated with IL dose, the rate of IL administration, and FFAu levels. TG and FFAu levels were higher in infants below 28 weeks' gestation Conclusions: Increasing dosage of IL is associated with increasing levels of TG and FFAu, especially in infants below 29 weeks of gestation. The increased level of FFAu suggests inefficient cellular utilization.

An APOC3 3′UTR variant associated with plasma triglycerides levels and coronary heart disease by creating a functional miR-4271 binding site

PubMed Central

Hu, Sen-Lin; Cui, Guang-Lin; Huang, Jin; Jiang, Jian-Gang; Wang, Dao-Wen

2016-01-01

Apolipoprotein C-III (APOC3) is a key regulator of plasma triglycerides levels. Increasing evidence has shown that loss-of-function mutations in APOC3 is associated with reduction in plasma triglycerides levels and will confer a benefit in patients at high risk for cardiovascular disease. However, these favorable mutations were extremely distribution discrepant among different ethnics. In this study, the APOC3 gene was resequenced and we identified a common variant which located in the microRNA-binding site in APOC3 and would affect its expression and the risk of coronary heart disease (CHD). The molecular mechanism was explored. We found that the T allele of rs4225 suppressed APOC3 translation by facilitating miR-4271 binding, but not the G allele. Subjects carrying the GG genotype had higher plasma APOC3 levels (p for trend = 0.03) than those with the TT genotype. Furthermore, the T allele was significantly associated with decreased triglyceride levels [Beta (SE): −0.024 (0.020), P = 0.03]. Finally, the case-control study suggested that the TT genotype resulted in a significant reduction in overall CHD risk [OR, 0.89 (95% confidence interval, 0.77–0.98), P = 0.009]. In conclusion, our results provide evidence that the rs4225 in the 3′-UTR of APOC3 might contribute to the risk of CHD by interfering with miR-4271 binding. PMID:27624799

An APOC3 3'UTR variant associated with plasma triglycerides levels and coronary heart disease by creating a functional miR-4271 binding site.

PubMed

Hu, Sen-Lin; Cui, Guang-Lin; Huang, Jin; Jiang, Jian-Gang; Wang, Dao-Wen

2016-09-14

Apolipoprotein C-III (APOC3) is a key regulator of plasma triglycerides levels. Increasing evidence has shown that loss-of-function mutations in APOC3 is associated with reduction in plasma triglycerides levels and will confer a benefit in patients at high risk for cardiovascular disease. However, these favorable mutations were extremely distribution discrepant among different ethnics. In this study, the APOC3 gene was resequenced and we identified a common variant which located in the microRNA-binding site in APOC3 and would affect its expression and the risk of coronary heart disease (CHD). The molecular mechanism was explored. We found that the T allele of rs4225 suppressed APOC3 translation by facilitating miR-4271 binding, but not the G allele. Subjects carrying the GG genotype had higher plasma APOC3 levels (p for trend = 0.03) than those with the TT genotype. Furthermore, the T allele was significantly associated with decreased triglyceride levels [Beta (SE): -0.024 (0.020), P = 0.03]. Finally, the case-control study suggested that the TT genotype resulted in a significant reduction in overall CHD risk [OR, 0.89 (95% confidence interval, 0.77-0.98), P = 0.009]. In conclusion, our results provide evidence that the rs4225 in the 3'-UTR of APOC3 might contribute to the risk of CHD by interfering with miR-4271 binding.

Atherogenic dyslipidemia: prevalence and management in lipid clinics.

PubMed

Pedro-Botet, J; Flores-Le Roux, J A; Mostaza, J M; Pintó, X; de la Cruz, J J; Banegas, J R

2014-12-01

Atherogenic dyslipidemia, which is characterized by increased triglyceride levels and reduced HDL cholesterol levels, is underestimated and undertreated in clinical practice. We assessed its prevalence and the achievement of therapeutic objectives for HDL cholesterol and triglyceride levels in patients treated at lipid and vascular risk units in Spain. This was an observational, longitudinal, retrospective, multicenter study performed in 14 autonomous Spanish communities that consecutively included 1828 patients aged ≥18 years who were referred for dyslipidemia and vascular risk to 43 lipid clinics accredited by the Spanish Society of Arteriosclerosis. We collected information from the medical records corresponding to 2 visits conducted during 2010 and 2011-12, respectively. Of the 1649 patients who had a lipid profile in the first visit (90.2%), 295 (17.9%) had atherogenic dyslipidemia. The factors associated with atherogenic dyslipidemia were excess weight/obesity, not taking hypolipidemic drugs (statins and/or fibrates), diabetes, myocardial infarction and previous heart failure. Of the 273 (92.5%) patients with atherogenic dyslipidemia that had a lipid profile in the last visit, 44 (16.1%) achieved the therapeutic objectives for HDL cholesterol and triglyceride levels. The predictors of therapeutic success were normal weight and normoglycemia. One of every 6 patients treated in lipid and vascular risk units had atherogenic dyslipidemia. The degree to which the therapeutic goals for HDL cholesterol and triglyceride levels were achieved in these patients was very low. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus.

PubMed

Lampman, R M; Schteingart, D E

1991-06-01

Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

Dietary anthocyanin-rich Haskap phytochemicals inhibit postprandial hyperlipidemia and hyperglycemia in rats.

PubMed

Takahashi, Azusa; Okazaki, Yukako; Nakamoto, Aika; Watanabe, Sanae; Sakaguchi, Hirohide; Tagashira, Yukari; Kagii, Atsuko; Nakagawara, Shunji; Higuchi, Ohki; Suzuki, Takashi; Chiji, Hideyuki

2014-01-01

Haskap (Lonicera caerulea L.) fruit contains some bioactive phenolic phytochemicals, mainly cyanidin-3-glucoside (cy3-glc) and chlorogenic acid. The purpose of this study was to investigate the effects of anthocyanin-rich phenolic phytochemical (containing 13.2% anthocyanin) purified from a Haskap fruit (named Haskap phytochemical) on postprandial serum triglyceride and blood glucose levels. The Haskap phytochemical (containing cy 3-glc at 300 mg/kg of body weight) was administered orally to rats fasted for 24 h and 30 min later, a corn oil emulsion was administered to these rats. After the administration, serum triglyceride concentration was measured. An increase in serum triglyceride concentration and the AUC significantly lowered in the Haskap phytochemical-administered group than in the saline-administered group. To evaluate the effect of serum glucose levels, the Haskap phytochemical was orally administered to rats fasted for 24 h and sucrose solution (2 g/kg of body weight) was administered to these rats after 30 min. After the administration, blood glucose level was measured. The Haskap phytochemical significantly reduced the increase in blood glucose levels and AUC in the Haskap phytochemical-administered group than in the saline-administered group. Furthermore, to investigate the long-term effects of Haskap phytochemical intake, high-fat diet (HF diet) with 1.5% or 3.0% Haskap phytochemical was administered to rats for four weeks. The investigation of chronological changes in the serum components of the rats fed HF diets in addition to the administration of Haskap phytochemical showed that the increase in serum triglyceride concentrations, total cholesterol concentrations and blood glucose were significantly suppressed compared to the HF diet-fed control (HF-control). These results suggest that the decrease in postprandial blood lipids and blood glucose by short or long-term Haskap phytochemical ingestion is due to anthocyanin and other polyphenols contained in the Haskap phytochemical.

Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses--A Case-Control Study.

PubMed

Gao, Ting; Jin, Kairui; Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

2015-01-01

Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. A total of 460 permanent residents of the Fengxian District, aged 40-60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18-28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism.

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.

Activated AMPK and prostaglandins are involved in the response to conjugated linoleic acid and are sufficient to cause lipid reductions in adipocytes.

PubMed

Jiang, Shan; Chen, Han; Wang, Zhigang; Riethoven, Jean-Jack; Xia, Yuannan; Miner, Jess; Fromm, Michael

2011-07-01

trans-10, cis-12 Conjugated linoleic acid (t10c12 CLA) reduces triglyceride levels in adipocytes. AMP-activated protein kinase (AMPK) and inflammation were recently demonstrated to be involved in the emerging pathways regulating this response. This study further investigated the role of AMPK and inflammation by testing the following hypotheses: (1) a moderate activation of AMPK and an inflammatory response are sufficient to reduce triglycerides, and (2) strong activation of AMPK is also sufficient. Experiments were performed by adding compounds that affect these pathways and by measuring their effects in 3T3-L1 adipocytes. A comparison of four AMPK activators (metformin, phenformin, TNF-α and t10c12 CLA) found a correlation between AMPK activity and triglyceride reduction. This correlation appeared to be modulated by the level of cyclo-oxygenase (COX)-2 mRNA produced. Inhibitors of the prostaglandin (PG) biosynthetic pathway interfered with t10c12 CLA's ability to reduce triglycerides. A combination of metformin and PGH2, or phenformin alone, efficiently reduced triglyceride levels in adipocytes. Microarray analysis indicated that the transcriptional responses to phenformin or t10c12 CLA were very similar, suggesting similar pathways were activated. 3T3-L1 fibroblasts were found to weakly induce the integrated stress response (ISR) in response to phenformin or t10c12 CLA and to respond robustly as they differentiated into adipocytes. This indicated that both chemicals required adipocytes at the same stage of differentiation to be competent for this response. These results support the above hypotheses and suggest compounds that moderately activate AMPK and increase PG levels or robustly activate AMPK in adipocytes may be beneficial for reducing adiposity. Copyright © 2011 Elsevier Inc. All rights reserved.

Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humans

PubMed Central

Stanhope, Kimber L.; Schwarz, Jean Marc; Keim, Nancy L.; Griffen, Steven C.; Bremer, Andrew A.; Graham, James L.; Hatcher, Bonnie; Cox, Chad L.; Dyachenko, Artem; Zhang, Wei; McGahan, John P.; Seibert, Anthony; Krauss, Ronald M.; Chiu, Sally; Schaefer, Ernst J.; Ai, Masumi; Otokozawa, Seiko; Nakajima, Katsuyuki; Nakano, Takamitsu; Beysen, Carine; Hellerstein, Marc K.; Berglund, Lars; Havel, Peter J.

2009-01-01

Studies in animals have documented that, compared with glucose, dietary fructose induces dyslipidemia and insulin resistance. To assess the relative effects of these dietary sugars during sustained consumption in humans, overweight and obese subjects consumed glucose- or fructose-sweetened beverages providing 25% of energy requirements for 10 weeks. Although both groups exhibited similar weight gain during the intervention, visceral adipose volume was significantly increased only in subjects consuming fructose. Fasting plasma triglyceride concentrations increased by approximately 10% during 10 weeks of glucose consumption but not after fructose consumption. In contrast, hepatic de novo lipogenesis (DNL) and the 23-hour postprandial triglyceride AUC were increased specifically during fructose consumption. Similarly, markers of altered lipid metabolism and lipoprotein remodeling, including fasting apoB, LDL, small dense LDL, oxidized LDL, and postprandial concentrations of remnant-like particle–triglyceride and –cholesterol significantly increased during fructose but not glucose consumption. In addition, fasting plasma glucose and insulin levels increased and insulin sensitivity decreased in subjects consuming fructose but not in those consuming glucose. These data suggest that dietary fructose specifically increases DNL, promotes dyslipidemia, decreases insulin sensitivity, and increases visceral adiposity in overweight/obese adults. PMID:19381015

Relationships between coronary heart disease risk factors and serum ionized calcium in Kennedy Space Center Cohort

NASA Technical Reports Server (NTRS)

Goodwin, Lisa Ann; Frey, Mary Anne Bassett; Merz, Marion P.; Alford, William R.

1987-01-01

Kennedy Space Center (KSC) employees are reported to be at high risk for coronary heart disease (CHD). Risk factors for CHD include high serum total cholesterol levels, low levels of high-density lipoprotein cholesterol (HDLC), elevated triglyceride, smoking, inactivity, high blood pressure, being male, and being older. Higher dietary and/or serum calcium Ca(++) may be related to a lower risk for CHD. Fifty men and 37 women participated. Subjects were tested in the morning after fasting 12 hours. Information relative to smoking and exercise habits was obtained; seated blood pressures were measured; and blood drawn. KCS men had higher risk values than KCS women as related to HDLC, triglycerides, systolic blood pressure, and diastolic blood pressure. Smoking and nonsmoking groups did not differ for other risk factors or for serum Ca(++) levels. Exercise and sedentary groups differed in total cholesterol and triglyceride levels. Serum Ca(++) levels were related to age, increasing with age in the sedentary group and decreasing in the exercisers, equally for men and women. It is concluded that these relationships may be significant to the risk of CHD and/or the risk of bone demineralization in an aging population.

Development, food intake, and ethinylestradiol influence hepatic triglyceride lipase and LDL-receptor mRNA levels in rats.

PubMed

Staels, B; Jansen, H; van Tol, A; Stahnke, G; Will, H; Verhoeven, G; Auwerx, J

1990-07-01

The influence of development and ethinylestradiol on low density lipoprotein (LDL)-receptor mRNA and hepatic triglyceride lipase (HTGL) activity and mRNA levels was studied in rat liver and intestine. Intestinal LDL-receptor mRNA levels are maximal in the perinatal period, whereas liver LDL-receptor and HTGL mRNA levels are highest after weaning in adult life. All mRNA levels reach a maximum between day 15 and 20 when rats still consume a lipid-rich diet, and increase twofold during weaning. Liver and intestinal LDL-receptor mRNA levels are not influenced by ovariectomy, but increase after ethinylestradiol treatment. Liver LDL-receptor mRNA shows a dose-dependent increase after ethinylestradiol and a sevenfold rise in liver LDL-receptor mRNA is attained with a dose of 2000 micrograms/day. Intestinal LDL-receptor mRNA increases slightly more than twofold after ethinylestradiol and this increase is not dose-dependent. Changes in LDL-receptor mRNA are independent of changes in food intake induced by ethinylestradiol treatment, since they are still observed after pair-feeding. The ethinylestradiol-induced increases in LDL-receptor mRNA levels are reflected by decreased serum apoB levels. HTGL mRNA levels increase after ovariectomy and show a dose-dependent decrease after ethinylestradiol. Pair-feeding abolishes the increase seen after ovariectomy, while the estrogen-mediated decrease is attenuated. These alterations in HTGL mRNA are reflected by similar changes in liver HTGL activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of comfort food on food intake, anxiety-like behavior and the stress response in rats.

PubMed

Ortolani, D; Oyama, L M; Ferrari, E M; Melo, L L; Spadari-Bratfisch, R C

2011-07-06

It has been suggested that access to high caloric food attenuates stress response. The present paper investigates whether access to commercial chow enriched with glucose and fat, here referred to as comfort food alters behavioral, metabolic, and hormonal parameters of rats submitted to three daily sessions of foot-shock stress. Food intake, anxiety-like behaviors, and serum levels of insulin, leptin, corticosterone, glucose and triglycerides were determined. The rats submitted to stress decreased the intake of commercial chow, but kept unaltered the intake of comfort food. During the elevated plus maze (EPM) test, stressed rats increased the number of head dipping, entries into the open arms, as well as the time spent there, and decreased the number of stretched-attend posture and risk assessment. These effects of stress were independent of the type of food consumed. Non-stressed rats ingesting comfort food decreased risk assessment as well. Stress and comfort food increased time spent in the center of the open field and delayed the first crossing to a new quadrant. Stress increased the plasma level of glucose and insulin, and reduced triglycerides, although consumption of comfort food increases glucose, triglyceride and leptin levels; no effect on leptin level was associated to stress. The stress induced increase in serum corticosterone was attenuated when rats had access to comfort food. It was concluded that foot-shock stress has an anorexigenic effect that is independent of leptin and prevented upon access to comfort food. Foot-shock stress also has an anxiolytic effect that is potentiated by the ingestion of comfort food and that is evidenced by both EPM and open field tests. Copyright © 2011 Elsevier Inc. All rights reserved.

Adipocyte Triglyceride Turnover Is Independently Associated With Atherogenic Dyslipidemia

PubMed Central

Frayn, Keith; Bernard, Samuel; Spalding, Kirsty; Arner, Peter

2012-01-01

Background Inappropriate storage of fatty acids as triglycerides in adipocytes and their removal from adipocytes through lipolysis and subsequent oxidation may cause the atherogenic dyslipidemia phenotype of elevated apolipoprotein B levels and subsequent hypertriglyceridemia. We tested whether turnover of triglycerides in fat cells was related to dyslipidemia. Methods and Results The age of triglycerides (reflecting removal) and triglyceride storage in adipocytes was determined under free living conditions by measuring incorporation of atmospheric 14C into these lipids within the adipocytes in 47 women and 26 men with a large interindividual variability in body mass index. Because limited 14C data were available, triglyceride age was also determined in 97 men and 233 women by using an algorithm based on adipocyte lipolysis, body fat content, waist‐to‐hip ratio, and insulin sensitivity. This cohort consisted of nonobese subjects since obesity per se is related to all components in the algorithm. Triglyceride turnover (age and storage) was compared with plasma levels of apolipoproteins and lipids. Plasma levels of apolipoprotein B and triglycerides were positively related to triglyceride age in adipocytes, when measured directly using radiocarbon analyses (r=0.45 to 0.47; P<0.0001). This effect was independent of subject age, waist circumference measures, and insulin sensitivity (partial r=0.29 to 0.45; P from 0.03 to <0.0001). Triglyceride storage showed no independent correlation (partial r=0.02 to 0.11; P=0.42 to 0.91). Algorithm‐based values for adipocyte removal of triglycerides were positively associated with plasma triglycerides and apolipoprotein B (r=0.44 to 0.45; P<0.0001) and (also positively) with the inflammation status of adipose tissue (r=0.39 to 0.47; P<0.05). These correlations were statistically independent of subject age and observed in men and women as well as in lean and overweight subjects when subgroups were examined separately. Conclusions Decreased removal of adipocyte triglycerides (as indicated by a high triglyceride age in fat cells) is independently associated with circulating apolipoprotein B and triglycerides. This suggests a hitherto unknown role of triglyceride turnover in adipocytes for the development and/or maintenance of atherogenic dyslipidemia. PMID:23316323

Apolipoprotein C-III Levels and Incident Coronary Artery Disease Risk: The EPIC-Norfolk Prospective Population Study.

PubMed

van Capelleveen, Julian C; Bernelot Moens, Sophie J; Yang, Xiaohong; Kastelein, John J P; Wareham, Nicholas J; Zwinderman, Aeilko H; Stroes, Erik S G; Witztum, Joseph L; Hovingh, G Kees; Khaw, Kay-Tee; Boekholdt, S Matthijs; Tsimikas, Sotirios

2017-06-01

Apolipoprotein C-III (apoC-III) is a key regulator of triglyceride metabolism. Elevated triglyceride-rich lipoproteins and apoC-III levels are causally linked to coronary artery disease (CAD) risk. The mechanism(s) through which apoC-III increases CAD risk remains largely unknown. The aim was to confirm the association between apoC-III plasma levels and CAD risk and to explore which lipoprotein subfractions contribute to this relationship between apoC-III and CAD risk. Plasma apoC-III levels were measured in baseline samples from a nested case-control study in the European Prospective Investigation of Cancer (EPIC)-Norfolk study. The study comprised 2711 apparently healthy study participants, of whom 832 subsequently developed CAD. We studied the association of baseline apoC-III levels with incident CAD risk, lipoprotein subfractions measured by nuclear magnetic resonance spectroscopy and inflammatory biomarkers. ApoC-III levels were significantly associated with CAD risk (odds ratio, 1.91; 95% confidence interval, 1.48-2.48 for highest compared with lowest quintile), retaining significance after adjustment for traditional CAD risk factors (odds ratio, 1.47; 95% confidence interval, 1.11-1.94). ApoC-III levels were positively correlated with triglyceride levels, ( r =0.39), particle numbers of very-low-density lipoprotein ( r =0.25), intermediate-density lipoprotein ( r =0.23), small dense low-density lipoprotein ( r =0.26), and high-sensitivity C-reactive protein ( r =0.15), whereas an inverse correlation was observed with large low-density lipoprotein particle number ( r =-0.11), P <0.001 for each. Mediation analysis indicated that the association between apoC-III and CAD risk could be explained by triglyceride elevation (triglyceride, very-low-density lipoprotein, and intermediate-density lipoprotein particles), small low-density lipoprotein particle size, and high-sensitivity C-reactive protein. ApoC-III levels are significantly associated with incident CAD risk. Elevated levels of remnant lipoproteins, small dense low-density lipoprotein, and low-grade inflammation may explain this association. © 2017 American Heart Association, Inc.

Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

PubMed

Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

2011-08-01

To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

The Effects of Gonadotropin Replacement Therapy on Metabolic Parameters and Body Composition in Men with Idiopathic Hypogonadotropic Hypogonadism.

PubMed

Bayram, F; Elbuken, G; Korkmaz, C; Aydogdu, A; Karaca, Z; Cakır, I

2016-02-01

Testosterone replacement therapy (TRT) in idiopathic hypogonadotrophic hypogonadism (IHH) slows the process of metabolic syndrome (MetS), diabetes mellitus, and cardiovascular diseases by its inversing effects on insulin resistance, dyslipidemia, and blood pressure. Since there are not enough data regarding the effects of gonadotropin replacement therapy (GRT), we aimed to investigate the impact of GRT on MetS parameters in IHH patients. Sixteen patients with IHH and 20 age and body mass index (BDI)-matched healthy controls were enrolled into the study. Patients were evaluated at baseline and 6 months after the GRT. Sex hormones, insulin like growth factor-1, prolactin, insulin, C-reactive protein (CRP), homocysteine, and lipid levels were measured at baseline and after the treatment. Anthropometric measurements, including BMI, body fat ratio (BFR), fat free mass (FFM), waist circumference, and waist-to-hip ratio (WHR), were also performed. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. Body fat ratio, triglyceride, HOMA-IR, and CRP levels were higher, whereas bone age, fat free mass, and creatinine levels were lower in the patients with hypogonadism. HOMA-IR indices and basal insulin levels decreased significantly after 6 months of GRT compared with baseline levels. Triglyceride levels, and BFRs diminished significantly by an accompanying decline in WHR. FFM of the patients increased following the GRT. No significant changes were detected in CRP, homocysteine, total and LDL-cholesterol levels. Similar to TRT, hCG treatment decreases HOMA-IR, triglyceride levels, BFR and WHRs, and increases FFM in patients with IHH. © Georg Thieme Verlag KG Stuttgart · New York.

Inactivating Variants in ANGPTL4 and Risk of Coronary Artery Disease

PubMed Central

Dewey, Frederick E.; Gusarova, Viktoria; O’Dushlaine, Colm; Gottesman, Omri; Trejos, Jesus; Hunt, Charleen; Van Hout, Cristopher V.; Habegger, Lukas; Buckler, David; Lai, Ka-Man V.; Leader, Joseph B.; Murray, Michael F.; Ritchie, Marylyn D.; Kirchner, H. Lester; Ledbetter, David H.; Penn, John; Lopez, Alexander; Borecki, Ingrid B.; Overton, John D.; Reid, Jeffrey G.; Carey, David J.; Murphy, Andrew J.; Yancopoulos, George D.; Baras, Aris; Gromada, Jesper; Shuldiner, Alan R.

2016-01-01

BACKGROUND Higher-than-normal levels of circulating triglycerides are a risk factor for ischemic cardiovascular disease. Activation of lipoprotein lipase, an enzyme that is inhibited by angiopoietin-like 4 (ANGPTL4), has been shown to reduce levels of circulating triglycerides. METHODS We sequenced the exons of ANGPTL4 in samples obtain from 42,930 participants of predominantly European ancestry in the DiscovEHR human genetics study. We performed tests of association between lipid levels and the missense E40K variant (which has been associated with reduced plasma triglyceride levels) and other inactivating mutations. We then tested for associations between coronary artery disease and the E40K variant and other inactivating mutations in 10,552 participants with coronary artery disease and 29,223 controls. We also tested the effect of a human monoclonal antibody against ANGPTL4 on lipid levels in mice and monkeys. RESULTS We identified 1661 heterozygotes and 17 homozygotes for the E40K variant and 75 participants who had 13 other monoallelic inactivating mutations in ANGPTL4. The levels of triglycerides were 13% lower and the levels of high-density lipoprotein (HDL) cholesterol were 7% higher among carriers of the E40K variant than among noncarriers. Carriers of the E40K variant were also significantly less likely than noncarriers to have coronary artery disease (odds ratio, 0.81; 95% confidence interval, 0.70 to 0.92; P = 0.002). K40 homozygotes had markedly lower levels of triglycerides and higher levels of HDL cholesterol than did heterozygotes. Carriers of other inactivating mutations also had lower triglyceride levels and higher HDL cholesterol levels and were less likely to have coronary artery disease than were noncarriers. Monoclonal antibody inhibition of Angptl4 in mice and monkeys reduced triglyceride levels. CONCLUSIONS Carriers of E40K and other inactivating mutations in ANGPTL4 had lower levels of triglycerides and a lower risk of coronary artery disease than did noncarriers. The inhibition of Angptl4 in mice and monkeys also resulted in corresponding reductions in these values. (Funded by Regeneron Pharmaceuticals.) PMID:26933753

Biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs.

PubMed

Gatto, Mariana; de Abreu, Mariana Miziara; Tasca, Karen Ingrid; Simão, José Cláudio; Fortaleza, Carlos Magno Castelo Branco; Pereira, Paulo Câmara Marques; Calvi, Sueli Aparecida

2013-01-01

Visceral leishmaniasis (VL) is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA) to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

Discovery of a novel series of benzimidazole derivatives as diacylglycerol acyltransferase inhibitors.

PubMed

Lee, Kyeong; Goo, Ja-Il; Jung, Hwa Young; Kim, Minkyoung; Boovanahalli, Shanthaveerappa K; Park, Hye Ran; Kim, Mun-Ock; Kim, Dong-Hyun; Lee, Hyun Sun; Choi, Yongseok

2012-12-15

A novel series of benzimidazole derivatives was prepared and evaluated for their diacylglycerol acyltransferase (DGAT) inhibitory activity using microsome from rat liver. Among the newly synthesized compounds, furfurylamine containing benzimidazole carboxamide 10j showed the most potent DGAT inhibitory effect (IC(50)=4.4 μM) and inhibited triglyceride formation in HepG2 cells. Furthermore, compound 10j reduced body weight gain of Institute of Cancer Research mice on a high-fat diet and decreased levels of total triglyceride, total cholesterol, and LDL-cholesterol in the blood accompanied with a significant increase in HDL-cholesterol level. Copyright © 2012 Elsevier Ltd. All rights reserved.

Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

PubMed Central

McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

2014-01-01

Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides.

PubMed

McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

2014-01-01

Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain.

Serum hepcidin levels are associated with serum triglycerides and interleukin-6 concentrations in patients with end-stage renal disease.

PubMed

Samouilidou, Elisabeth; Pantelias, Konstantinos; Petras, Dimitrios; Tsirpanlis, George; Bakirtzi, Joulia; Chatzivasileiou, George; Tzanatos, Helen; Grapsa, Eirini

2014-06-01

Hepcidin has emerged as a peptide with a key role in the regulation of iron homeostasis in patients with chronic kidney disease (CKD), having a strong dependence on inflammation. Recent studies reveal that hepcidin may be also associated with the progression of atherosclerosis. This study was performed to analyze the relation of hepcidin to markers of atherosclerosis and inflammation in patients on dialysis. A total of 90 individuals were enrolled. Sixty patients with end-stage renal disease, who were on hemodialysis (HD) (N = 30) and peritoneal dialysis (N = 30) were compared with 30 normal controls (NC). Age, body mass index, time on dialysis, serum lipids, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured and analyzed in correlation with hepcidin concentration. It was found that patients on HD and peritoneal dialysis have significantly higher (P < 0.0001) levels of hepcidin, CRP and IL-6 than NC. Hepcidin in dialysis patients is significantly related to age (r = 0.373, P = 0.012), serum triglycerides (r = 0.401, P = 0.005), HDL-C (r = -0.268, P = 0.048), CRP (r = 0.436, P = 0.0007) and IL-6 (r = 0.569, P < 0.0001). In multiple regression analysis, hepcidin correlated independently with triglycerides (β = 0.402, P = 0.041) and IL-6 (β = 0.559, P = 0.006). Moreover, patients with high triglycerides in combination with high IL-6 levels have significantly increased concentrations of hepcidin than those with low triglycerides and low IL-6 levels (P < 0.0001). Elevated levels of hepcidin in patients with CKD on dialysis may be related to the occurrence of high triglycerides and high IL-6 serum concentrations. This probably suggests that hepcidin may play a role to the progression of atherosclerosis and inflammation, but this hypothesis should be further evaluated. © 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.

Triglycerides as an early pathophysiological marker of endothelial dysfunction in nondiabetic women with a previous history of gestational diabetes.

PubMed

Sokup, Alina; Góralczyk, Barbara; Góralczyk, Krzysztof; Rość, Danuta

2012-02-01

To investigate whether baseline triglyceride levels are associated with early glucose dysregulation and/or cardiovascular risk in women with a previous history of gestational diabetes. Prospective postpregnancy cohort study. Polish university hospitals. Participants included 125 women with previous gestational diabetes and 40 women with normal glucose regulation during pregnancy. All women were studied 2-24 months (mean 12 ± 10 months) after the index pregnancy. Women with previous gestational diabetes were divided into tertiles in accordance with baseline triglyceride levels. We assessed glucose regulation (oral glucose tolerance test), insulin resistance (homeostasis model assessment), markers of endothelial dysfunction (soluble: intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, tissue plasminogen activator antigen, von Willebrand factor antigen), fibrinolysis (plasminogen activator inhibitor antigen), inflammation (high-sensitivity C-reactive protein) and lipid levels. Women with previous gestational diabetes (78% normal glucose regulation, 22% impaired glucose tolerance) had a high cardiometabolic risk profile compared with control women (100% normal glucose regulation). Baseline triglycerides >0.83 mmol/l were associated with a higher prevalence of impaired glucose tolerance, higher high-sensitivity C-reactive protein and triglyceride/high-density lipoprotein-cholesterol ratio. Triglycerides >1.22 mmol/l were associated with higher body fat indexes, higher insulin resistance, higher levels of endothelial dysfunction biomarkers, higher plasminogen activator inhibitor antigen and dyslipidemia. Only E-selectin was independently associated with triglyceride levels. Baseline triglyceride levels are a cardiovascular risk marker as well as a pathophysiological parameter independently associated with endothelial dysfunction in nondiabetic women with previous gestational diabetes at 2-24 months after an index pregnancy. Normalization of triglycerides should be included in preventive therapy after a pregnancy complicated by gestational diabetes. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

Treatment of hypertriglyceridemia-induced acute pancreatitis with insulin

PubMed Central

Erkan, Nazif; Yakan, Savas; Yildirim, Mehmet; Carti, Erdem; Ucar, Deniz; Oymaci, Erkan

2015-01-01

Introduction Hypertriglyceridaemia (HT)-induced pancreatitis rarely occurs unless triglyceride levels exceed 1000 mg/dl. Hypertriglyceridaemia over 1,000 mg/dl can provoke acute pancreatitis (AP) and its persistence can worsen the clinical outcome. In contrast, a rapid decrease in triglyceride level is beneficial. Insulin-stimulated lipoprotein lipase is known to decrease serum triglyceride levels. However, their efficacy in HT-induced AP is not well documented. Aim To present 12 cases of AP successfully treated by insulin administration. Material and methods Three hundred and forty-three cases of AP were diagnosed at our clinic between 2005 and 2012. Twelve (3.5%) of these cases were HT-induced AP. Twelve patients who suffered HT-induced AP are reported. Initial blood triglyceride levels were above 1000 mg/dl. Besides the usual treatment of AP, insulin was administered intravenously in continuous infusion. The patients’ medical records were retrospectively evaluated in this study. Results Serum triglyceride levels decreased to < 500 mg/dl within 2–3 days. No complications of treatment were seen and good clinical outcome was observed. Conclusions Our results are compatible with the literature. Insulin may be used safely and effectively in HT-induced AP therapy. Administration of insulin is efficient when used to reduce triglyceride levels in patients with HT-induced AP. PMID:25960810

Correlation between non-alcoholic fatty liver disease (NAFLD) and dyslipidemia in type 2 diabetes.

PubMed

Krishan, Saini

2016-01-01

Non-alcoholic fatty liver means the presence of hepatosteatosis without significant alcohol consumption; it is strongly associated with obesity and metabolic disorder like type 2 diabetes and dyslipideamia. NASH may progress to advanced stages of hepatic fibrosis and cirrhosis. Increased body mass index and viral genotype contribute to steatosis in chronic hepatitis. The sonographic features of NAFLD include the presence of bright hepatic echotexture deep attenuation, and vascular blurring either singly or in combination. Dyslipidemia in patients with NAFLD is atherogenic in nature and it is characterized by increased levels of serum triglycerides and decreased levels of HDL cholesterol. Statins are potent lipid-lowering agents which decrease LDL cholesterol by 20-60%, decrease triglycerides by 10-33% and increase HDL cholesterol by 5-10% for the patients with NAFLD. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Effect of various kinds of beverages on stress oxidative, F2 isoprostane, serum lipid and blood glucose of elite taekwondo players.

PubMed

Maghsoudi, Zahra; Shiranian, Ashfin; Askai, Gholamreza; Ghaisvand, Reza

2016-01-01

Athletes' recovery is important in improving their performance. Nutritional strategies can be effective in enhancing recovery rate. Choosing the best food items in appropriate intervals can play effective roles in resynthesis of fuels and recovery of muscle injury. Beverage micro and macronutrient content are helpful in fuel restoration. In this study, we assess the effects of various kinds of beverages on oxidative stress, muscle injury, and metabolic risk factors in taekwondo players. This quasi-experimental study was performed on 21 taekwondo players of Isfahan. After collecting fasting blood, they performed runningbased anaerobic sprint test (RAST). Blood lactate was tested again and participants were divided into 3 intervention groups, that is, receiving 500 cc dough, non-alcoholic beer, and chocolate milk at 4 day intervals. After a 2-h recovery period, blood sampling was repeated. Elites consumed other beverages in later phases. Dietary intake and fasting triglyceride, cholesterol, blood sugar, lactate dehydrogenase, and F 2 -isoprostane concentrations were determined. Data were analyzed with a simple repeated-measures test and post-hoc tests using the Statistical Package for the Social Sciences software. Data showed that cholesterol levels non-significantly decreased after intervention. Triglyceride level was lower after taking dough and carbohydrate replacement drink. Blood glucose concentration increased after intervention periods, however, this increase was significant only after non-alcoholic beverage consumption. Lactate dehydrogenase levels reduced after all cycles, however, F 2 -isoprostane level showed no significant change. There was not significant change in lactate dehydrogenase and F 2 -isoprostane levels. Non-alcoholic beer consumption can reduce lactate dehydrogenase concentration; however, it leads to blood sugar increase. Moreover, dough consumption significantly reduced triglyceride level in taekwondo players.

[Changes in serum lipids in rats treated with oral cooper].

PubMed

Alarcón-Corredor, O M; Carnevalí de Tatá, E; Reinosa-Füller, J; Contreras, Y; Ramírez de Fernández, M; Yánez-Domínguez, C

2000-09-01

Disturbances in lipid metabolism during copper deficiency in rats are well recognized. Copper deficiency is associated with the spontaneous retention of hepatic iron. Previous studies have reported that hypercholesterolemia and hypertriglyceridemia are associated with elevated hepatic iron concentrations in copper deficient rats. There was a direct relationship between the magnitude of blood lipids and the concentration of hepatic iron. Based on these data, it has been hypothesized that iron was responsible for the development of lipemia of copper deficiency. In this study was determined the effect of increasing doses of Cu(10, 20 and 50 ppm) in the diet, on the serum total lipids, total cholesterol, triglycerides (triacylglicerols), phospholipids, non-esterified fatty acids (NEFA) and liver iron and zinc concentrations in normal rats. The results were compared with normal rats that received a balanced diet containing 0.6 and 6 ppm of Cu, respectively. The results show that Cu-supplement diminished the cholesterol and triglyceride serum levels, increased the level of phospholipids, NEFA and concomitantly decreased the hepatic concentrations of Fe and Zn. There was a statistically significant (p < 0.05) simple correlation between triglycerides and liver Fe (r = 0.917; R2 = 64.03%), cholesterol and liver Zn (r = 0.872; R2 = 76.07%), cholesterol and liver Fe (r = 0.995; R2 = 99.10%), liver Fe and liver Cu (r = -0.612), liver Fe and liver Zn (r = 0.837), liver Cu and liver Zn (r = -0.612), and serum triglycerides and liver Zn (r = 0.967). The mechanism(s) by which Fe and Zn determine these changes is not known; none of the enzymes that act in cholesterol and triglyceride metabolism and biosynthesis require Fe and/or Zn. The increase of NEFA is due to changes in the process of lipolysis and re-esterification of the fatty acids in blood. However, additional studies are needed for the precise mechanisms of this interrelationships to be clarified.

Characterizing the nutritional strategy of incubating king eiders Somateria spectabilis in northern Alaska

USGS Publications Warehouse

Bentzen, R.L.; Powell, A.N.; Williams, T.D.; Kitaysky, A.S.

2008-01-01

We measured plasma concentrations of variables associated with lipid metabolism (free fatty acids, glycerol, triglyceride, and ??- hydroxybutyrate), protein metabolism (uric acid), and baseline corticosterone to characterize the nutritional state of incubating king eiders Somateria spectabilis and relate this to incubation constancy at two sites, Kuparuk and Teshekpuk, in northern Alaska. King eiders at both sites appeared to employ a partial-income incubation strategy, relying on both endogenous and exogenous energy resources. Females maintained high invariant levels of free fatty acids, ??-hydroxybutyrate, and glycerol throughout incubation, indicating that fat reserves were a major energy source, and not completely depleted during incubation. Similarly, uric acid did not increase, suggesting effective protein sparing or protein ingestion and adequate lipid reserves throughout incubation. Baseline corticosterone and triglyceride levels increased during incubation, indicative of an increase in foraging during late stages of incubation. Incubating females at Kuparuk had higher triglyceride concentrations but also had higher ??-hydroxybutyrate concentrations than females at Teshekpuk. This dichotomy may reflect a short-term signal of feeding overlaying the longer-term signal of reliance on endogenous lipid reserves due to higher food intake yet higher metabolic costs at Kuparuk because of its colder environment. Incubation constancy was not correlated with plasma concentrations of lipid or protein metabolites. ?? 2008 The Authors.

Sensations induced by medium and long chain triglycerides: role of gastric tone and hormones

PubMed Central

Barbera, R; Peracchi, M; Brighenti, F; Cesana, B; Bianchi, P; Basilisco, G

2000-01-01

BACKGROUND—The relative roles of gastric relaxation and the neuroendocrine signals released by the small intestine in the perception of nutrient induced sensations are controversial. The different effects of long chain (LCT) and medium chain (MCT) triglyceride ingestion on perception, gastric relaxation, and hormonal release may help to elucidate the mechanisms underlying nutrient induced sensations.
AIMS—To compare the effects of intraduodenal LCT and MCT infusions on perception, gastric tone, and plasma gut hormone levels in healthy subjects.
SUBJECTS—Nine fasting healthy volunteers.
METHODS—The subjects received duodenal infusions of saline followed by LCTs and MCTs in a randomised order on two different days. The sensations were rated on a visual analogue scale. Gastric tone was measured using a barostat, and plasma gut hormone levels by radioimmunoassay.
RESULTS—LCT infusion increased satiation scores, reduced gastric tone, and increased the levels of plasma cholecystokinin, gastric inhibitory polypeptide, neurotensin, and pancreatic polypeptide. MCT infusion reduced gastric tone but did not significantly affect perception or plasma gut hormone levels. LCTs produced greater gastric relaxation than MCTs.
CONCLUSIONS—The satiation induced by intraduodenal LCT infusion seems to involve changes in gastric tone and plasma gut hormone levels. The gastric relaxation induced by MCT infusion, together with the absence of any significant change in satiation scores and plasma hormone levels, suggests that, at least up to a certain level, gastric relaxation is not sufficient to induce satiation and that nutrient induced gastric relaxation may occur through cholecystokinin independent mechanisms.


Keywords: gastric tone; triglyceride; hormones; satiation; cholecystokinin; nutrients PMID:10601051

Functional analysis of the TRIB1 associated locus linked to plasma triglycerides and coronary artery disease.

PubMed

Douvris, Adrianna; Soubeyrand, Sébastien; Naing, Thet; Martinuk, Amy; Nikpay, Majid; Williams, Andrew; Buick, Julie; Yauk, Carole; McPherson, Ruth

2014-06-03

The TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease in humans. The lipid-associated single nucleotide polymorphisms (SNPs), identified by genome-wide association studies, are located ≈30 kb downstream from TRIB1, suggesting complex regulatory effects on genes or pathways relevant to hepatic triglyceride metabolism. The goal of this study was to investigate the functional relationship between common SNPs at the TRIB1 locus and plasma lipid traits. Characterization of the risk locus reveals that it encompasses a gene, TRIB1-associated locus (TRIBAL), composed of a well-conserved promoter region and an alternatively spliced transcript. Bioinformatic analysis and resequencing identified a single SNP, rs2001844, within the promoter region that associates with increased plasma triglycerides and reduced high-density lipoprotein cholesterol and coronary artery disease risk. Further, correction for triglycerides as a covariate indicated that the genome-wide association studies association is largely dependent on triglycerides. In addition, we show that rs2001844 is an expression trait locus (eQTL) for TRIB1 expression in blood and alters TRIBAL promoter activity in a reporter assay model. The TRIBAL transcript has features typical of long noncoding RNAs, including poor sequence conservation. Modulation of TRIBAL expression had limited impact on either TRIB1 or lipid regulatory genes mRNA levels in human hepatocyte models. In contrast, TRIB1 knockdown markedly increased TRIBAL expression in HepG2 cells and primary human hepatocytes. These studies demonstrate an interplay between a novel locus, TRIBAL, and TRIB1. TRIBAL is located in the genome-wide association studies identified risk locus, responds to altered expression of TRIB1, harbors a risk SNP that is an eQTL for TRIB1 expression, and associates with plasma triglyceride concentrations. © 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Functional Analysis of the TRIB1 Associated Locus Linked to Plasma Triglycerides and Coronary Artery Disease

PubMed Central

Douvris, Adrianna; Soubeyrand, Sébastien; Naing, Thet; Martinuk, Amy; Nikpay, Majid; Williams, Andrew; Buick, Julie; Yauk, Carole; McPherson, Ruth

2014-01-01

Background The TRIB1 locus has been linked to hepatic triglyceride metabolism in mice and to plasma triglycerides and coronary artery disease in humans. The lipid‐associated single nucleotide polymorphisms (SNPs), identified by genome‐wide association studies, are located ≈30 kb downstream from TRIB1, suggesting complex regulatory effects on genes or pathways relevant to hepatic triglyceride metabolism. The goal of this study was to investigate the functional relationship between common SNPs at the TRIB1 locus and plasma lipid traits. Methods and Results Characterization of the risk locus reveals that it encompasses a gene, TRIB1‐associated locus (TRIBAL), composed of a well‐conserved promoter region and an alternatively spliced transcript. Bioinformatic analysis and resequencing identified a single SNP, rs2001844, within the promoter region that associates with increased plasma triglycerides and reduced high‐density lipoprotein cholesterol and coronary artery disease risk. Further, correction for triglycerides as a covariate indicated that the genome‐wide association studies association is largely dependent on triglycerides. In addition, we show that rs2001844 is an expression trait locus (eQTL) for TRIB1 expression in blood and alters TRIBAL promoter activity in a reporter assay model. The TRIBAL transcript has features typical of long noncoding RNAs, including poor sequence conservation. Modulation of TRIBAL expression had limited impact on either TRIB1 or lipid regulatory genes mRNA levels in human hepatocyte models. In contrast, TRIB1 knockdown markedly increased TRIBAL expression in HepG2 cells and primary human hepatocytes. Conclusions These studies demonstrate an interplay between a novel locus, TRIBAL, and TRIB1. TRIBAL is located in the genome‐wide association studies identified risk locus, responds to altered expression of TRIB1, harbors a risk SNP that is an eQTL for TRIB1 expression, and associates with plasma triglyceride concentrations. PMID:24895164

Cholesterol, APOE genotype, and Alzheimer disease: an epidemiologic study of Nigerian Yoruba.

PubMed

Hall, K; Murrell, J; Ogunniyi, A; Deeg, M; Baiyewu, O; Gao, S; Gureje, O; Dickens, J; Evans, R; Smith-Gamble, V; Unverzagt, F W; Shen, J; Hendrie, H

2006-01-24

To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. Logistic regression models showed interaction after adjusting for age and gender between APOE-epsilon4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p= 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-epsilon4 allele, but not in those with APOE-epsilon4. There was no significant association between levels of triglycerides and AD risk in those without APOE-epsilon4. There was a significant interaction between cholesterol, APOE-epsilon4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies.

Cholesterol, APOE genotype, and Alzheimer disease

PubMed Central

Hall, K.; Murrell, J.; Ogunniyi, A.; Deeg, M.; Baiyewu, O.; Gao, S.; Gureje, O.; Dickens, J.; Evans, R.; Smith-Gamble, V.; Unverzagt, F.W.; Shen, J.; Hendrie, H.

2010-01-01

Objective To examine the relationship between cholesterol and other lipids, APOE genotype, and risk of Alzheimer disease (AD) in a population-based study of elderly Yoruba living in Ibadan, Nigeria. Methods Blood samples and clinical data were collected from Yoruba study participants aged 70 years and older (N = 1,075) as part of the Indianapolis-Ibadan Dementia Project, a longitudinal epidemiologic study of AD. Cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride levels were measured in fasting blood samples. DNA was extracted and APOE was genotyped. Diagnoses of AD were made by consensus using National Institute of Neurologic Disorders/Stroke-Alzheimer's Disease and Related Disorders Association criteria. Results Logistic regression models showed interaction after adjusting for age and gender between APOE-ε4 genotype and biomarkers in the risk of AD cholesterol*genotype (p = 0.022), LDL*genotype (p = 0.018), and triglyceride*genotype (p = 0.036). Increasing levels of cholesterol and LDL were associated with increased risk of AD in individuals without the APOE-ε4 allele, but not in those with APOE-ε4. There was no significant association between levels of triglycerides and AD risk in those without APOE-ε4. Conclusions There was a significant interaction between cholesterol, APOE-ε4, and the risk of Alzheimer disease (AD) in the Yoruba, a population that has lower cholesterol levels and lower incidence rates of AD compared to African Americans. APOE status needs to be considered when assessing the relationship between lipid levels and AD risk in population studies. PMID:16434658

Effect of Hibiscus sabdariffa on obesity in MSG mice.

PubMed

Alarcon-Aguilar, Francisco J; Zamilpa, Alejandro; Perez-Garcia, Ma Dolores; Almanza-Perez, Julio C; Romero-Nuñez, Eunice; Campos-Sepulveda, Efrain A; Vazquez-Carrillo, Laura I; Roman-Ramos, Ruben

2007-10-08

The aim of the present investigation was determine whether a standardized Hibiscus sabdariffa calyces aqueous extract has an effect on body weight in an obese animal model induced by the administration of monosodium glutamate. Hibiscus sabdariffa aqueous extract, containing 33.64 mg of total anthocyanins per each 120 mg of extract, was orally administered (120 mg/kg/day) for 60 days to healthy and obese mice, and body weight gain, food and liquid intake, aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholesterol, and triglycerides levels were measured. Hibiscus sabdariffa administration significantly reduced body weight gain in obese mice and increased liquid intake in healthy and obese mice. ALT levels were significantly increased on the 15th and 45th days in obese mice, but AST levels did not show significant changes. Mortality was not observed in the Hibiscus sabdariffa treated groups. Triglycerides and cholesterol levels showed non-significant reductions in animals treated with Hibiscus sabdariffa. Our data confirm the anti-obesity effect of Hibiscus sabdariffa reported by the Mexican population.

Effects of gluten-free breads, with varying functional supplements, on the biochemical parameters and antioxidant status of rat serum.

PubMed

Świeca, Michał; Reguła, Julita; Suliburska, Joanna; Złotek, Urszula; Gawlik-Dziki, Urszula

2015-09-01

This paper examines the effects of gluten-free bread enriched with functional ingredients (milk powder, poppy, sunflower and pumpkin seeds, egg yolk, carum, hazel nuts and amaranth) on the morphological and biochemical parameters and antioxidant status of rats serum. Rats were provided test diets--gluten-free breads and water ad libitum. After 14 days, the animals were weighed and killed. A hazel nut-amaranth bread diet significantly increased the level of thrombocytes when compared to control bread. A mixed bread diet significantly decreased cholesterol levels in rats. All fortified breads decreased triglyceride levels and alanine transaminase activity and caused an increase in antiradical activity of the serum. In rats fed with poppy-milk bread, milk-seed bread and mixed bread, a marked decrease in superoxide dismutase activity was found. Enriched breads reduced the levels of triglyceride and improved the antiradical properties of serum, although the physiological relevance of this needs to be confirmed by human studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling the influence of APOC3, APOE, and TNF polymorphisms on the risk of antiretroviral therapy-associated lipid disorders.

PubMed

Tarr, Philip E; Taffé, Patrick; Bleiber, Gabriela; Furrer, Hansjakob; Rotger, Margalida; Martinez, Raquel; Hirschel, Bernard; Battegay, Manuel; Weber, Rainer; Vernazza, Pietro; Bernasconi, Enos; Darioli, Roger; Rickenbach, Martin; Ledergerber, Bruno; Telenti, Amalio

2005-05-01

Single-nucleotide polymorphisms in genes involved in lipoprotein and adipocyte metabolism may explain why dyslipidemia and lipoatrophy occur in some but not all antiretroviral therapy (ART)-treated individuals. We evaluated the contribution of APOC3 -482C-->T, -455T-->C, and 3238C-->G; epsilon 2 and epsilon 4 alleles of APOE; and TNF -238G-->A to dyslipidemia and lipoatrophy by longitudinally modeling >2600 lipid determinations and 2328 lipoatrophy assessments in 329 ART-treated patients during a median follow-up period of 3.4 years. In human immunodeficiency virus (HIV)-infected individuals, the effects of variant alleles of APOE on plasma cholesterol and triglyceride levels and of APOC3 on plasma triglyceride levels were comparable to those reported in the general population. However, when treated with ritonavir, individuals with unfavorable genotypes of APOC3 and [corrected] APOE were at risk of extreme hypertriglyceridemia. They had median plasma triglyceride levels of 7.33 mmol/L, compared with 3.08 mmol/L in the absence of ART. The net effect of the APOE*APOC3*ritonavir interaction was an increase in plasma triglyceride levels of 2.23 mmol/L. No association between TNF -238G-->A and lipoatrophy was observed. Variant alleles of APOE and APOC3 contribute to an unfavorable lipid profile in patients with HIV. Interactions between genotypes and ART can lead to severe hyperlipidemia. Genetic analysis may identify patients at high risk for severe ritonavir-associated hypertriglyceridemia.

The polymorphism -1131T>C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects.

PubMed

Ferreira, Cláudia N; Carvalho, Maria G; Fernandes, Ana P; Santos, Izabela R; Rodrigues, Kathryna F; Lana, Angela M Q; Almeida, Cristina R; Loures-Vale, Andréia A; Gomes, Karina B; Sousa, Marinez O

2013-03-01

Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 -1131T>C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia. We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student-Newman-Keuls test. The minor allele C was more frequent in dyslipidemic subjects than controls (p=0.019) and confers an increased individual risk for dyslipidemia (OR=1.726, CI 95%=1.095-2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p=0.037; OR=2.050, CI 95%=1.042-4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p=0.046 and 0.049, respectively). The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 -1131T>C polymorphism is associated with dyslipidemia in male subjects. Copyright © 2012 Elsevier B.V. All rights reserved.

OSBPL10, a novel candidate gene for high triglyceride trait in dyslipidemic Finnish subjects, regulates cellular lipid metabolism.

PubMed

Perttilä, Julia; Merikanto, Krista; Naukkarinen, Jussi; Surakka, Ida; Martin, Nicolas W; Tanhuanpää, Kimmo; Grimard, Vinciane; Taskinen, Marja-Riitta; Thiele, Christoph; Salomaa, Veikko; Jula, Antti; Perola, Markus; Virtanen, Ismo; Peltonen, Leena; Olkkonen, Vesa M

2009-08-01

Analysis of variants in three genes encoding oxysterol-binding protein (OSBP) homologues (OSBPL2, OSBPL9, OSBPL10) in Finnish families with familial low high-density lipoprotein (HDL) levels (N = 426) or familial combined hyperlipidemia (N = 684) revealed suggestive linkage of OSBPL10 single-nucleotide polymorphisms (SNPs) with extreme end high triglyceride (TG; >90th percentile) trait. Prompted by this initial finding, we carried out association analysis in a metabolic syndrome subcohort (Genmets) of Health2000 examination survey (N = 2,138), revealing association of multiple OSBPL10 SNPs with high serum TG levels (>95th percentile). To investigate whether OSBPL10 could be the gene underlying the observed linkage and association, we carried out functional experiments in the human hepatoma cell line Huh7. Silencing of OSBPL10 increased the incorporation of [(3)H]acetate into cholesterol and both [(3)H]acetate and [(3)H]oleate into triglycerides and enhanced the accumulation of secreted apolipoprotein B100 in growth medium, suggesting that the encoded protein ORP10 suppresses hepatic lipogenesis and very-low-density lipoprotein production. ORP10 was shown to associate dynamically with microtubules, consistent with its involvement in intracellular transport or organelle positioning. The data introduces OSBPL10 as a gene whose variation may contribute to high triglyceride levels in dyslipidemic Finnish subjects and provides evidence for ORP10 as a regulator of cellular lipid metabolism.

Involvement of glucocorticoid prereceptor metabolism and signaling in rat visceral adipose tissue lipid metabolism after chronic stress combined with high-fructose diet.

PubMed

Bursać, Biljana; Djordjevic, Ana; Veličković, Nataša; Milutinović, Danijela Vojnović; Petrović, Snježana; Teofilović, Ana; Gligorovska, Ljupka; Preitner, Frederic; Tappy, Luc; Matić, Gordana

2018-05-03

Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats. We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes. Blood triglycerides and fatty acid composition were also measured to assess hepatic Δ9 desaturase activity. The results showed that fructose diet increased blood triglycerides and Δ9 desaturase activity. On the other hand, stress led to corticosterone elevation, glucocorticoid receptor activation and decrease in adipocyte size, while phosphoenolpyruvate carboxykinase, adipose tissue triglyceride lipase, FAT/CD36 and sterol regulatory element binding protein-1c (SREBP-1c) were increased, pointing to VAT lipolysis and glyceroneogenesis. The combination of stress and fructose diet was associated with marked stimulation of fatty acid synthase and acetyl-CoA carboxylase mRNA level and with increased 11β-hydroxysteroid dehydrogenase type 1 and hexose-6-phosphate dehydrogenase protein levels, suggesting a coordinated increase in hexose monophosphate shunt and de novo lipogenesis. It however did not influence the level of peroxisome proliferator-activated receptor-gamma, SREBP-1c and carbohydrate responsive element-binding protein. In conclusion, our results showed that only combination of dietary fructose and stress increase glucocorticoid prereceptor metabolism and stimulates lipogenic enzyme expression suggesting that interaction between stress and fructose may be instrumental in promoting VAT expansion and dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Isotretinoin kinetics after 80 to 320 mg oral doses.

PubMed

Colburn, W A; Gibson, D M

1985-04-01

Twelve healthy male subjects received 80, 160, 240, and 320 mg doses of oral isotretinoin as multiples of 40 mg capsules separated by 2-week washout periods in a randomized, crossover design. Blood samples were drawn at specific times over a 72-hour period after dosing. Blood concentrations of isotretinoin as well as its major metabolite, 4-oxo-isotretinoin, were determined by a specific HPLC method. In addition to the normal laboratory battery of tests, serum triglyceride levels were determined before the first dose and again 72 hours after each of the four doses. Mean (+/- SD) maximum concentrations after 80 to 320 mg doses were 366 +/- 159, 820 +/- 474, 1056 +/- 547, and 981 +/- 381 ng/ml, whereas the respective AUC0-infinity values were 3690 +/- 1280, 7030 +/- 4140, 9780 +/- 6080, and 9040 +/- 2900 ng X hr/ml. The observed apparent elimination t1/2 remained approximately the same (14.7 hours) for each dose. The maximum concentration and AUC values for isotretinoin appear to be dose proportional from 80 to 240 mg but plateau at the 320 mg dose level. Therefore, because isotretinoin blood concentrations may not increase with higher doses in the fasting state, single, oral doses in excess of 240 mg should be used with caution. The data also suggest that elevated triglyceride levels are not a simple function of isotretinoin blood concentrations across the entire study population and dose range studied, but that in subjects with triglyceride levels in excess of the normal range triglyceride levels were positively related to isotretinoin blood concentrations.

Peripheral arterial disease, type 2 diabetes and postprandial lipidaemia: Is there a link?

PubMed Central

Valdivielso, Pedro; Ramírez-Bollero, José; Pérez-López, Carmen

2014-01-01

Peripheral arterial disease, manifested as intermittent claudication or critical ischaemia, or identified by an ankle/brachial index < 0.9, is present in at least one in every four patients with type 2 diabetes mellitus. Several reasons exist for peripheral arterial disease in diabetes. In addition to hyperglycaemia, smoking and hypertension, the dyslipidaemia that accompanies type 2 diabetes and is characterised by increased triglyceride levels and reduced high-density lipoprotein cholesterol concentrations also seems to contribute to this association. Recent years have witnessed an increased interest in postprandial lipidaemia, as a result of various prospective studies showing that non-fasting triglycerides predict the onset of arteriosclerotic cardiovascular disease better than fasting measurements do. Additionally, the use of certain specific postprandial particle markers, such as apolipoprotein B-48, makes it easier and more simple to approach the postprandial phenomenon. Despite this, only a few studies have evaluated the role of postprandial triglycerides in the development of peripheral arterial disease and type 2 diabetes. The purpose of this review is to examine the epidemiology and risk factors of peripheral arterial disease in type 2 diabetes, focusing on the role of postprandial triglycerides and particles. PMID:25317236

Vitamin A degradation in triglycerides varying by their saturation levels.

PubMed

Moccand, Cyril; Martin, Fréderic; Martiel, Isabelle; Gancel, Charlotte; Michel, Martin; Fries, Lennart; Sagalowicz, Laurent

2016-10-01

Vitamin A deficiency has a widespread occurrence globally and is considered as one of the world's most serious health risk factors. Potential solutions to address this deficiency include dietary diversification or supplementation, but food fortification is generally accepted as the most cost-effective solution. The main issue with food fortification of this vitamin is related to its high instability in food matrices. Dilution of vitamin A in triglycerides is a natural and appropriate way to stabilize this compound. We show here that vitamin A palmitate stability increases with increasing concentration of triglycerides. Moreover, we found that vitamin A palmitate displays improved stability in more saturated oils. Using various temperatures, and Arrhenius plots of experiments performed at storage temperatures between 30°C and 60°C for oils varying by their saturation and crystallinity, we demonstrate that crystallization is not responsible for this phenomenon. Additionally, we show by centrifugation that vitamin A is preferably solubilized in the liquid phase compared to the crystalline phase, explaining that triglyceride crystallization does not stabilize vitamin A palmitate. It is proposed that unsaturated fats generate more oxidation products such as radicals and peroxides, leading to a quicker degradation of vitamin A. Copyright © 2016 Elsevier Ltd. All rights reserved.

Target molecules in 3T3-L1 adipocytes differentiation are regulated by maslinic acid, a natural triterpene from Olea europaea.

PubMed

Pérez-Jiménez, Amalia; Rufino-Palomares, Eva E; Fernández-Gallego, Nieves; Ortuño-Costela, M Carmen; Reyes-Zurita, Fernando J; Peragón, Juan; García-Salguero, Leticia; Mokhtari, Khalida; Medina, Pedro P; Lupiáñez, José A

2016-11-15

Metabolic syndrome is a set of pathologies among which stand out the obesity, which is related to the lipid droplet accumulation and changes to cellular morphology regulated by several molecules and transcription factors. Maslinic acid (MA) is a natural product with demonstrated pharmacological functions including anti-inflammation, anti-tumor and anti-oxidation, among others. Here we report the effects of MA on the adipogenesis process in 3T3-L1 cells. Cell viability, glucose uptake, cytoplasmic triglyceride droplets, triglycerides quantification, gene transcription factors such as peroxisome proliferator-activated receptor γ (PPARγ) and adipocyte fatty acid-binding protein (aP2) and intracellular Ca 2+ levels were determined in pre-adipocytes and adipocytes of 3T3-L1 cells. MA increased glucose uptake. MA also decreased lipid droplets and triglyceride levels, which is in concordance with the down-regulation of PPARγ and aP2. Finally, MA increased the intracellular Ca 2+ concentration, which could also be involved in the demonstrated antiadipogenic effect of this triterpene. MA has been demonstrated as potential antiadipogenic compound in 3T3-L1 cells. Copyright © 2016 Elsevier GmbH. All rights reserved.

Serum total cholesterol and triglycerides levels in patients with lung cancer.

PubMed

Siemianowicz, K; Gminski, J; Stajszczyk, M; Wojakowski, W; Goss, M; Machalski, M; Telega, A; Brulinski, K; Magiera-Molendowska, H

2000-02-01

Epidemiological studies indicate that low serum total cholesterol level may increase the risk of death due to cancer, mainly lung cancer. The aim of our study was to evaluate serum levels of total cholesterol (TC) and triglycerides (TG) in patients with squamous cell and small cell lung cancer and their dependence on the histological type and the clinical stage of the neoplasm. Lung cancer patients (n=135) and healthy controls (n=39) entered the study. All lung cancer patients had higher rate of hypocholesterolemia and lower TC and TG levels than the control group. TC concentration was lower in lung cancer patients and in both histological types in comparison with the control group, TG level was lower only in patients with squamous cell lung cancer. There were no statistically significant differences of TC and TG levels between the histological types, or between the clinical stages of each histological type.

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

Kimura, Rino; Takahashi, Nobuyuki, E-mail: nobu@kais.kyoto-u.ac.jp; Murota, Kaeko

Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of fatty acid oxidation-related genes in human intestinal epithelial Caco-2 cells. {yields} PPAR{alpha} activation also increased oxygen consumption rate and CO{sub 2} production and decreased secretion of triglyceride and ApoB from Caco-2 cells. {yields} Orally administration of bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and CO{sub 2} production in small intestinal epithelial cells. {yields} Treatment with bezafibrate decreased postprandial serum concentration of triglyceride after oral injection of olive oil in mice. {yields} It suggested that intestinal lipid metabolism regulated by PPAR{alpha} activation suppresses postprandial lipidemia. -- Abstract: Activation ofmore » peroxisome proliferator-activated receptor (PPAR)-{alpha} which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPAR{alpha} activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPAR{alpha} activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPAR{alpha} agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO{sub 2} and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPAR{alpha} activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPAR{alpha} activity is a novel target of PPAR{alpha} agonist for decreasing circulating levels of lipids under postprandial conditions.« less

Effects of Castration on Expression of Lipid Metabolism Genes in the Liver of Korean Cattle

PubMed Central

Baik, Myunggi; Nguyen, Trang Hoa; Jeong, Jin Young; Piao, Min Yu; Kang, Hyeok Joong

2015-01-01

Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration. PMID:25557684

Circulating CD34-positive cells, glomerular filtration rate and triglycerides in relation to hypertension.

PubMed

Shimizu, Yuji; Sato, Shimpei; Koyamatsu, Jun; Yamanashi, Hirotomo; Nagayoshi, Mako; Kadota, Koichiro; Maeda, Takahiro

2015-11-01

Serum triglycerides have been reported to be independently associated with the development of chronic kidney disease (CKD), which is known to play a role in vascular disturbance. On the other hand, circulating CD34-positve cells, including endothelial progenitor cells, are reported to contribute to vascular repair. However, no studies have reported on the correlation between triglycerides and the number of CD34-positive cells. Since hypertension is well known factor for vascular impairment, the degree of correlation between serum triglycerides and circulating CD34-positve cells should account for hypertension status. We conducted a cross-sectional study of 274 elderly Japanese men aged ≥ 60 years (range 60-79 years) undergoing general health checkups. Multiple linear regression analysis of non-hypertensive subjects adjusting for classical cardiovascular risk factors showed that although triglyceride levels (1SD increments; 64 mg/dL) did not significantly correlate with glomerular filtration rate (GFR) (β = -2.06, p = 0.163), a significant positive correlation was seen between triglycerides and the number of circulating CD34-positive cells (β = 0.50, p = 0.004). In hypertensive subjects, a significant inverse correlation between triglycerides and GFR was observed (β = -2.66, p = 0.035), whereas no significant correlation between triglycerides and the number of circulating CD34-positive cells was noted (β = -0.004, p = 0.974). Since endothelial progenitor cells (CD34-positive cells) have been reported to contribute to vascular repair, our results indicate that in non-hypertensive subjects, triglycerides may stimulate an increase in circulating CD34-positive cells (vascular repair) by inducing vascular disturbance. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Reduced Expression of Adipose Triglyceride Lipase Enhances Tumor Necrosis Factor α-induced Intercellular Adhesion Molecule-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C-dependent Activation of Nuclear Factor-κB*

PubMed Central

Inoue, Tomoaki; Kobayashi, Kunihisa; Inoguchi, Toyoshi; Sonoda, Noriyuki; Fujii, Masakazu; Maeda, Yasutaka; Fujimura, Yoshinori; Miura, Daisuke; Hirano, Ken-ichi; Takayanagi, Ryoichi

2011-01-01

We examined the effects of adipose triglyceride lipase (ATGL) on the initiation of atherosclerosis. ATGL was recently identified as a rate-limiting triglyceride (TG) lipase. Mutations in the human ATGL gene are associated with neutral lipid storage disease with myopathy, a rare genetic disease characterized by excessive accumulation of TG in multiple tissues. The cardiac phenotype, known as triglyceride deposit cardiomyovasculopathy, shows massive TG accumulation in both coronary atherosclerotic lesions and the myocardium. Recent reports show that myocardial triglyceride content is significantly higher in patients with prediabetes or diabetes and that ATGL expression is decreased in the obese insulin-resistant state. Therefore, we investigated the effect of decreased ATGL activity on the development of atherosclerosis using human aortic endothelial cells. We found that ATGL knockdown enhanced monocyte adhesion via increased expression of TNFα-induced intercellular adhesion molecule-1 (ICAM-1). Next, we determined the pathways (MAPK, PKC, or NFκB) involved in ICAM-1 up-regulation induced by ATGL knockdown. Both phosphorylation of PKC and degradation of IκBα were increased in ATGL knockdown human aortic endothelial cells. In addition, intracellular diacylglycerol levels and free fatty acid uptake via CD36 were significantly increased in these cells. Inhibition of the PKC pathway using calphostin C and GF109203X suppressed TNFα-induced ICAM-1 expression. In conclusion, we showed that ATGL knockdown increased monocyte adhesion to the endothelium through enhanced TNFα-induced ICAM-1 expression via activation of NFκB and PKC. These results suggest that reduced ATGL expression may influence the atherogenic process in neutral lipid storage diseases and in the insulin-resistant state. PMID:21828047

With medium-chain triglycerides, higher and faster oxygen radical production by stimulated polymorphonuclear leukocytes occurs.

PubMed

Kruimel, J W; Naber, A H; Curfs, J H; Wenker, M A; Jansen, J B

2000-01-01

Parenteral lipid emulsions are suspected of suppressing the immune function. However, study results are contradictory and mainly concern the conventional long-chain triglyceride emulsions. Polymorphonuclear leukocytes were preincubated with parenteral lipid emulsions. The influence of the lipid emulsions on the production of oxygen radicals by these stimulated leukocytes was studied by measuring chemiluminescence. Three different parenteral lipid emulsions were tested: long-chain triglycerides, a physical mixture of medium- and long-chain triglycerides, and structured triglycerides. Structured triglycerides consist of triglycerides where the medium- and long-chain fatty acids are attached to the same glycerol molecule. Stimulated polymorphonuclear leukocytes preincubated with the physical mixture of medium- and long-chain triglycerides showed higher levels of oxygen radicals (p < .005) and faster production of oxygen radicals (p < .005) compared with polymorphonuclear leukocytes preincubated with long-chain triglycerides or structured triglycerides. Additional studies indicated that differences in results of various lipid emulsions were not caused by differences in emulsifier. The overall production of oxygen radicals was significantly lower after preincubation with the three lipid emulsions compared with controls without lipid emulsion. A physical mixture of medium- and long-chain triglycerides induced faster production of oxygen radicals, resulting in higher levels of oxygen radicals, compared with long-chain triglycerides or structured triglycerides. This can be detrimental in cases where oxygen radicals play either a pathogenic role or a beneficial one, such as when rapid phagocytosis and killing of bacteria is needed. The observed lower production of oxygen radicals by polymorphonuclear leukocytes in the presence of parenteral lipid emulsions may result in immunosuppression by these lipids.

Circulating Betatrophin Correlates with Triglycerides and Postprandial Glucose among Different Glucose Tolerance Statuses—A Case-Control Study

PubMed Central

Chen, Peihong; Jin, Hua; Yang, Lili; Xie, Xinmiao; Yang, Meili; Hu, Cheng; Yu, Xuemei

2015-01-01

Purpose Previous researches of betatrophin on glucose and lipids metabolism under insulin-resistant condition have reached controversial conclusions. To further identify the possible impact of betatrophin, we measured the circulating betatrophin levels in newly diagnosed type 2 diabetes (T2DM) patients, and in subjects with both impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) and investigated the relationship between serum betatrophin and other clinical parameters in these patients with different glucose tolerance statuses. Methods A total of 460 permanent residents of the Fengxian District, aged 40–60 years, were enrolled. Based on the results of a 75 g oral glucose tolerance test, we selected newly diagnosed T2DM (n = 50) patients and subjects with IGT (n = 51) and NGT (n = 50) according to their age, gender and body mass index (18–28 kg/m2). Anthropometric parameters, glycosylated haemoglobin, blood lipids and fasting insulin were measured. Serum betatrophin concentrations were determined via ELISA. Results Serum betatrophin levels in T2DM patients were increased significantly compared with IGT and NGT groups, and decreased in subjects with better islet beta cell function. Serum betatrophin was positively correlated with triglyceride, 2-hour postprandial glucose, alanine aminotransferase and aspartate transaminase after adjusting for age, sex and body mass index in all subjects. Multiple regression analysis showed that 2-hour postprandial glucose was independently associated with serum betatrophin significantly. Conclusions Circulating betatrophin is increased in newly-diagnosed T2DM patients and positively correlated with the triglycerides and postprandial glucose levels. The results suggest that betatrophin may participate in glucose and triglycerides metabolism. PMID:26247824

Serum Myostatin Is Reduced in Individuals with Metabolic Syndrome

PubMed Central

Chiang, Chih-Kang; Tseng, Fen-Yu; Tseng, Ping-Huei; Chen, Chi-Ling; Wu, Kwan-Dun; Yang, Wei-Shiung

2014-01-01

Aims Myostatin is a negative regulator of skeletal muscle mass and may also modulate energy metabolism secondarily. We aim to investigate the relationship between serum myostatin and the metabolic variables in diabetic (DM) and non-diabetic subjects. Materials and Methods A cross-sectional study recruiting 246 consecutive DM patients and 82 age- and gender-matched non-diabetic individuals at a medical center was conducted. The variables of anthropometry and blood chemistry were obtained. Serum myostatin level was measured with enzyme immunoassay. Results DM group had lower serum myostatin compared with non-diabetics (7.82 versus 9.28 ng/ml, p<0.01). Sixty-two percent of the recruited individuals had metabolic syndrome (MetS). The patients with MetS had significantly lower serum myostatin than those without (7.39 versus 9.49 ng/ml, p<0.001). The serum myostatin level decreased with increasing numbers of the MetS components (p for trend<0.001). The patients with higher body mass index, larger abdominal girth, lower high-density lipoprotein cholesterol (HDL-C), and higher triglycerides had lower serum myostatin than those without. The serum myostatin level was independently negatively related to larger abdominal girth, higher triglycerides, and lower HDL-C after adjustment. The odds ratios for MetS, central obesity, low HDL-C, high triglycerides, and DM were 0.85, 0.88, 0.89, 0.85, and 0.92, respectively, when serum myostatin increased per 1 ng/mL, in the binary logistic regression models. Conclusions Lower serum myostatin independently associated with MetS, central obesity, low HDL-C, and high triglycerides after adjustment. Higher serum myostatin is associated with favorable metabolic profiles. PMID:25254550

Excessive fuel availability amplifies the FTO-mediated obesity risk: results from the TUEF and Whitehall II studies.

PubMed

Wagner, Róbert; Tabák, Ádám G; Fehlert, Ellen; Fritsche, Louise; Jaghutriz, Benjamin A; Bánhegyi, Róbert J; Schmid, Sebastian M; Staiger, Harald; Machicao, Fausto; Peter, Andreas; Häring, Hans-Ulrich; Fritsche, Andreas; Heni, Martin

2017-11-14

Variation in FTO is the most important common genetic determinant of body weight. Altered energy metabolism could underlie this association. We hypothesized that higher circulating glucose or triglycerides can amplify the FTO impact on BMI. In 2671 subjects of the TUEF study, we investigated the interaction effect of fasting glucose and triglyceride levels with rs9939609 in FTO on BMI. We analysed the same interaction effect by longitudinally utilizing mixed effect models in the prospective Whitehall II study. In TUEF, we detected an interaction effect between fasting glucose and fasting triglycerides with rs9939609 on BMI (p = 0.0005 and p = 5 × 10 -7 , respectively). The effect size of one risk allele was 1.4 ± 0.3 vs. 2.2 ± 0.44 kg/m² in persons with fasting glucose levels below and above the median, respectively. Fasting triglycerides above the median increased the per-allele effect from 1.4 ± 0.3 to 1.7 ± 0.4 kg/m 2 . In the Whitehall II study, body weight increased by 2.96 ± 6.5 kg during a follow-up of 13.5 ± 4.6 yrs. Baseline fasting glucose and rs9939609 interacted on weight change (p = 0.009). Higher fasting glucose levels may amplify obesity-risk in FTO carriers and lead to an exaggerated weight gain over time. Since weight gain perpetuates metabolic alterations, this interplay may trigger a vicious circle that leads to obesity and diabetes.

Effects of Diet High in Palmitoleic Acid on Serum Lipid Levels and Metabolism

DTIC Science & Technology

2000-07-01

cholesterol , high - density a typical American diet. lipoprotein cholesterol , and triglyceride ...group imbalance resulting from density lipoprotein ( HDL ) cholesterol , and triglyceride dropouts or exclusions during the run-in or early in the levels...Circulation 1997;95:69-75. 15. Austin MA, Rodriguez BL, McKnight B, JD Curb. Low- density lipoprotein (LDL) particle size and plasma triglyceride ( TG

Nitrogen dioxide induced changes in level of free fatty acids, triglyceride, esterified fatty acid, ganglioside and lipase activity in the guinea pig brain

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

Farahani, H.; Hasan, M.

1992-02-01

The biochemical response to controlled inhalation of nitrogen dioxide (NO2) was studied in 18 male guinea pigs. Animals were exposed to 2.5, 5.0, and 10 ppm NO2 for 2h daily for 35 consecutive days, and the results compared with six control animals exposed to filtered air for 2h daily for same period. Five biochemical parameters, including triglyceride, free fatty acids, esterified fatty acid, ganglioside and lipase activity were measured immediately after the last day of exposure. At 2.5 ppm NO2 inhalation no significant changes occurred in any region of the central nervous system (CNS). While as the dose concentration wasmore » increased to 5 and 10 ppm nitrogen dioxide, significant dose-related alteration were observed in the levels of triglyceride, free fatty acid, esterified fatty acid, ganglioside and lipase activity in the different regions of the guinea pig CNS.« less

The effect of exercise on plasma lipids and LDL subclass metabolism in miniature swine.

PubMed

Stucchi, A F; Terpstra, A H; Foxall, T L; Nicolosi, R J; Smith, S C

1991-05-01

The effects of exercise on plasma lipids and lipoproteins, high density lipoprotein (HDL) subclass cholesterol levels, and low density lipoprotein (LDL) subclass composition and metabolism were studied in Yucatan miniature swine following 2 yr of training. The exercise protocol produced significant training effects. Post-heparin lipolytic activity was also significantly increased. Although plasma cholesterol and triglycerides did not differ significantly (P = 0.08) between the exercised and control groups, multivariate analysis indicated a strong association between lipoprotein lipase (LPL) and HDL2-C (P less than 0.0001). Although HDL-C levels rose only slightly (P less than 0.09) with exercise, a significant shift was noted in the distribution of cholesterol from the HDL3 to the HDL2 fractions, perhaps mediated by the substantial increase in LPL activity. Exercise had little effect on the chemical composition of the major lipoprotein classes; however, the triglyceride content of the lighter LDL1 subclass was significantly reduced. In the more dense LDL2 subclass, exercise resulted in a significant decrease in triglycerides concomitant with a significant increase in free cholesterol levels. In contrast with the small reductions in fractional catabolic rates (FCR) in either subclass, production rates of the exercised group were reduced, which accounted for the reduction in LDL subclass pool size. These data indicate that exercise produces subtle but significant changes in lipoprotein metabolism that have been previously associated with reduced risk of atherosclerosis.

Differential effects of high-carbohydrate and high-fat diets on hepatic lipogenesis in rats.

PubMed

Ferramosca, Alessandra; Conte, Annalea; Damiano, Fabrizio; Siculella, Luisa; Zara, Vincenzo

2014-06-01

Hepatic fatty acid synthesis is influenced by several nutritional and hormonal factors. In this study, we have investigated the effects of distinct experimental diets enriched in carbohydrate or in fat on hepatic lipogenesis. Male Wistar rats were divided into four groups and fed distinct experimental diets enriched in carbohydrates (70% w/w) or in fat (20 and 35% w/w). Activity and expression of the mitochondrial citrate carrier and of the cytosolic enzymes acetyl-CoA carboxylase and fatty acid synthetase were analyzed through the study with assessments at 0, 1, 2, 4, and 6 weeks. Liver lipids and plasma levels of lipids, glucose, and insulin were assayed in parallel. Whereas the high-carbohydrate diet moderately stimulated hepatic lipogenesis, a strong inhibition of this anabolic pathway was found in animals fed high-fat diets. This inhibition was time-dependent and concentration-dependent. Moreover, whereas the high-carbohydrate diet induced an increase in plasma triglycerides, the high-fat diets determined an accumulation of triglycerides in liver. An increase in the plasmatic levels of glucose and insulin was observed in all cases. The excess of sucrose in the diet is converted into fat that is distributed by bloodstream in the organism in the form of circulating triglycerides. On the other hand, a high amount of dietary fat caused a strong inhibition of lipogenesis and a concomitant increase in the level of hepatic lipids, thereby highlighting, in these conditions, the role of liver as a reservoir of exogenous fat.

The composition and metabolism of large and small LDL

USDA-ARS?s Scientific Manuscript database

Decreased size and increased density of LDL have been associated with increased coronary heart disease (CHD) risk. Elevated plasma concentrations of small dense LDL (sdLDL) correlate with high plasma triglycerides and low HDL cholesterol levels. This review highlights recent findings about the met...

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.

Evidence for increased chylomicron remnants in rheumatoid arthritis.

PubMed

Burggraaf, Benjamin; van Breukelen-van der Stoep, Deborah F; van Zeben, Jendé; van der Meulen, Noelle; van de Geijn, Gert-Jan M; Liem, Anho; Valdivielso, Pedro; Rioja Villodres, José; Ramírez-Bollero, José; van der Zwan, Ellen; Castro Cabezas, Manuel

2018-02-01

Levels of apolipoprotein (apo) B48 may be increased in conditions associated with systemic inflammation and increased cardiovascular disease (CVD) risk such as rheumatoid arthritis (RA). We aimed to evaluate apo B48 levels in patients with RA in relation to subclinical atherosclerosis. Patients with RA (without CVD) and controls without RA but with high CVD risk (based on the presence of diabetes mellitus or a history of CVD) and healthy controls were included in this cross-sectional study. Carotid intima-media thickness (cIMT) was measured as a surrogate for vascular damage. In total, 312 patients with RA, 65 controls with high CVD risk and 36 healthy controls were included. Patients with RA had the highest mean apo B48 (10.00 ± 6.65 mg/L) compared to controls with high CVD risk and healthy controls (8.37 ± 5.16 and 5.22 ± 2.46, P < .001). Triglycerides levels were comparable with controls. In RA, apo B48 correlated positively with triglycerides (r = .645; P < .001) but not with cIMT. However, in RA subjects not using lipid or blood pressure lowering medication, a weak correlation was found with cIMT (r = .157; P = .014). RA patients in the highest apo B48 tertile were more often rheumatoid factor positive and anti-CCP positive compared to the lowest tertile. Rheumatoid arthritis patients have higher levels of apo B48 compared to controls with high CVD risk and healthy controls, with normal levels of triglycerides. This accumulation of atherogenic chylomicron remnants may contribute to the elevated CVD risk in RA patients. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

Longitudinal study of body mass index, dyslipidemia, hyperglycemia, and hypertension in 60,000 men and women in Sweden and Austria.

PubMed

Van Hemelrijck, Mieke; Ulmer, Hanno; Nagel, Gabriele; Peter, Raphael Simon; Fritz, Josef; Myte, Robin; van Guelpen, Bethany; Föger, Bernhard; Concin, Hans; Häggström, Christel; Stattin, Pär; Stocks, Tanja

2018-01-01

Obesity is suggested to underlie development of other metabolic aberrations, but longitudinal relationships between metabolic factors at various ages has not been studied in detail. Data from 27,379 men and 32,275 women with in total 122,940 health examinations in the Västerbotten Intervention Project, Sweden and the Vorarlberg Health Monitoring and Prevention Programme, Austria were used to investigate body mass index (BMI), mid-blood pressure, and fasting levels of glucose, triglycerides, and total cholesterol at baseline in relation to 10-year changes of these factors and weight. We included paired examinations performed 10±2 years apart and used them for longitudinal analysis with linear regression of changes between the ages 30 and 40, 40 and 50, or 50 and 60 years. Higher levels of BMI were associated with increases in glucose and mid-blood pressure as well as triglycerides levels, and, to a lesser extent, decreases in cholesterol levels. For instance, per 5 kg/m2 higher BMI at age 40, glucose at age 50 increased by 0.24 mmol/l (95%CI: 0.22-0.26) and mid-blood pressure increased by 1.54 mm Hg (95%CI: 1.35-1.74). The strongest association observed was between BMI at age 30 and mid-blood pressure, which was 2.12 mm Hg (95% CI: 1.79-2.45) increase over ten years per 5 kg/m2 higher BMI level. This association was observed at an age when blood pressure levels on average remained stable. Other associations than those with BMI at baseline were much weaker. However, triglyceride levels were associated with future glucose changes among individuals with elevated BMI, particularly in the two older age groups. BMI was most indicative of long-term changes in metabolic factors, and the strongest impact was observed for increases in blood pressure between 30 and 40 years of age. Our study supports that lifestyle interventions preventing metabolic aberrations should focus on avoiding weight increases.

Elevated triglycerides may affect cystatin C recovery.

PubMed

Witzel, Samantha H; Butts, Katherine; Filler, Guido

2014-05-01

The purpose of this study was to investigate the effect of triglyceride concentration on cystatin C (CysC) measurements. Serum samples collected from 10 nephrology patients, 43 to 78years of age, were air centrifuged to separate aqueous and lipid layers. The lipid layer from each patient was pooled together to create a mixture with a high triglyceride concentration. This pooled lipid layer was mixed with each of the ten patient aqueous layers in six different ratios. Single factor ANOVA was used to assess whether CysC recovery was affected by triglyceride levels. Regression analysis was used to develop a formula to correct for the effect of triglycerides on CysC measurement, based on samples from 6 randomly chosen patients from our study population. The formula was validated with the 4 remaining samples. The analysis revealed a significant reduction in measured CysC with increasing concentrations of triglycerides (Pearson r=-0.56, p<0.0001). The following formula was developed to correct for the effect of triglycerides: Subsequent Bland-Altman plots revealed a bias (mean±1 standard deviation [SD]) of -3.7±15.6% for the data used to generate the correction formula and a bias of 3.52±9.38% for the validation set. Our results suggest that triglyceride concentrations significantly impact cystatin C measurements and that this effect may be corrected in samples that cannot be sufficiently clarified by air centrifugation using the equation that we developed. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Independent effects of apolipoprotein AV and apolipoprotein CIII on plasma triglyceride concentrations

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

Baroukh, Nadine N.; Bauge, Eric; Akiyama, Jennifer

2003-08-15

Both the apolipoprotein A5 and C3 genes have repeatedly been shown to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered Both the apolipoprotein A5 and C3 genes have repeatedly been shownmore » to play an important role in determining plasma triglyceride concentrations in humans and mice. In mice, transgenic and knockout experiments indicate that plasma triglyceride levels are negatively and positively correlated with APOA5 and APOC3 expression, respectively. In humans, common polymorphisms in both genes have also been associated with plasma triglyceride concentrations. The evolutionary relationship among these two apolipoprotein genes and their close proximity on human chromosome 11q23 have largely precluded the determination of their relative contribution to altered triglycerides. To overcome these confounding factors and address their relationship, we generated independent lines of mice that either over-expressed (''double transgenic'') or completely lacked (''double knockout'') both apolipoprotein genes. We report that both ''double transgenic'' and ''double knockout'' mice display intermedia tetriglyceride concentrations compared to over-expression or deletion of either gene alone. Furthermore, we find that human ApoAV plasma protein levels in the ''double transgenic'' mice are approximately 500-fold lower than human ApoCIII levels, supporting ApoAV is a potent triglyceride modulator despite its low concentration. Together, these data indicate that APOA5 and APOC3 independently influence plasma triglyceride concentrations but in an opposing manner.« less

Matcha, a powdered green tea, ameliorates the progression of renal and hepatic damage in type 2 diabetic OLETF rats.

PubMed

Yamabe, Noriko; Kang, Ki Sung; Hur, Jong Moon; Yokozawa, Takako

2009-08-01

Matcha, a powdered green tea produced by grinding with a stone mill, has been popularly used in the traditional tea ceremony and foods in Japan. Matcha is well known to be richer in some nutritional elements and epigallocatechin 3-O-gallate than other green teas. In our previous study, epigallocatechin 3-O-gallate exhibited protective effects against renal damage in a rat model of diabetic nephropathy. In the present study, we investigated the preventive effects of Matcha (50, 100, or 200 mg/kg/day) on the progression of hepatic and renal damage in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. OLETF rats were orally administered Matcha for 16 weeks, and we assessed biochemical parameters in the serum, liver, and kidney and expression levels of major products of advanced glycation end products (AGEs), N(6)-(carboxylmethyl)lysine (CML) and N(6)-(carboxylethyl)lysine (CEL), receptor for AGE (RAGE), and sterol regulatory element binding proteins (SREBPs)-1 and -2. Serum total protein levels were significantly increased by Matcha administration, whereas the serum albumin and glycosylated protein levels as well as the renal glucose and triglyceride levels were only slightly or not at all affected. However, Matcha treatment significantly lowered the glucose, triglyceride, and total cholesterol levels in the serum and liver, renal AGE levels, and the serum thiobarbituric acid-reactive substances levels. In addition, Matcha supplementation resulted in decreases in the renal CML, CEL, and RAGE expressions as well as an increase in hepatic SREBP-2 expression, but not that of SREBP-1. These results suggest that Matcha protects against hepatic and renal damage through the suppression of renal AGE accumulation, by decreases in hepatic glucose, triglyceride, and total cholesterol levels, and by its antioxidant activities.

Medium-Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support In Vitro Synaptic Transmission During Acute Hypoglycemia

PubMed Central

Page, Kathleen A.; Williamson, Anne; Yu, Namyi; McNay, Ewan C.; Dzuira, James; McCrimmon, Rory J.; Sherwin, Robert S.

2009-01-01

OBJECTIVE We examined whether ingestion of medium-chain triglycerides could improve cognition during hypoglycemia in subjects with intensively treated type 1 diabetes and assessed potential underlying mechanisms by testing the effect of β-hydroxybutyrate and octanoate on rat hippocampal synaptic transmission during exposure to low glucose. RESEARCH DESIGN AND METHODS A total of 11 intensively treated type 1 diabetic subjects participated in stepped hyperinsulinemic- (2 mU · kg−1 · min−1) euglycemic- (glucose ∼5.5 mmol/l) hypoglycemic (glucose ∼2.8 mmol/l) clamp studies. During two separate sessions, they randomly received either medium-chain triglycerides or placebo drinks and performed a battery of cognitive tests. In vitro rat hippocampal slice preparations were used to assess the ability of β-hydroxybutyrate and octanoate to support neuronal activity when glucose levels are reduced. RESULTS Hypoglycemia impaired cognitive performance in tests of verbal memory, digit symbol coding, digit span backwards, and map searching. Ingestion of medium-chain triglycerides reversed these effects. Medium-chain triglycerides also produced higher free fatty acids and β-hydroxybutyrate levels compared with placebo. However, the increase in catecholamines and symptoms during hypoglycemia was not altered. In hippocampal slices β-hydroxybutyrate supported synaptic transmission under low-glucose conditions, whereas octanoate could not. Nevertheless, octanoate improved the rate of recovery of synaptic function upon restoration of control glucose concentrations. CONCLUSIONS Medium-chain triglyceride ingestion improves cognition without adversely affecting adrenergic or symptomatic responses to hypoglycemia in intensively treated type 1 diabetic subjects. Medium-chain triglycerides offer the therapeutic advantage of preserving brain function under hypoglycemic conditions without causing deleterious hyperglycemia. PMID:19223595

Inadequate Triglyceride Management Worsens the Durability of Dipeptidyl Peptidase-4 Inhibitor in Subjects with Type 2 Diabetes Mellitus.

PubMed

Shimoda, Masashi; Miyoshi-Takai, Maiko; Irie, Shintaro; Tanabe, Akihito; Obata, Atsushi; Okauchi, Seizo; Hirukawa, Hidenori; Kimura, Tomohiko; Kohara, Kenji; Kamei, Shinji; Mune, Tomoatsu; Kaku, Kohei; Kaneto, Hideaki

2017-01-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors are often used all over the world and exert various beneficial effects including glucose-lowering effect in many subjects with type 2 diabetes. It is poorly understood, however, which factors are closely related with the durability of glucose-lowering effect by DPP-4 inhibitor. In this study, we examined retrospectively which factors could mainly influence the durability of DPP-4 inhibitor. We enrolled 212 participants with type 2 diabetes to whom DPP-4 inhibitor was administered for over 1 year without an addition or increase of other hypoglycemic agents. Age and baseline HbA1c level were significantly higher in the effective group than those in the ineffective group. The effective group had a tendency of smaller amounts of weight change, average total cholesterol, and average triglyceride compared with the ineffective group. Multiple logistic regression analysis showed that average triglyceride and baseline HbA1c were independent predictors associated with the durability of DPP-4 inhibitor. Moreover, an average triglyceride level contributed to the durability of DPP-4 inhibitor in the obese group (BMI ≥ 25 kg/m 2 ) but not in the nonobese group (BMI < 25 kg/m 2 ). These results suggest the importance of strict triglyceride management to maintain the durability of glucose-lowering effect by DPP-4 inhibitor, especially in obese subjects with type 2 diabetes.

Caloric sweetener consumption and dyslipidemia among US adults.

PubMed

Welsh, Jean A; Sharma, Andrea; Abramson, Jerome L; Vaccarino, Viola; Gillespie, Cathleen; Vos, Miriam B

2010-04-21

Dietary carbohydrates have been associated with dyslipidemia, a lipid profile known to increase cardiovascular disease risk. Added sugars (caloric sweeteners used as ingredients in processed or prepared foods) are an increasing and potentially modifiable component in the US diet. No known studies have examined the association between the consumption of added sugars and lipid measures. To assess the association between consumption of added sugars and blood lipid levels in US adults. Cross-sectional study among US adults (n = 6113) from the National Health and Nutrition Examination Survey (NHANES) 1999-2006. Respondents were grouped by intake of added sugars using limits specified in dietary recommendations (< 5% [reference group], 5%-<10%, 10%-<17.5%, 17.5%-<25%, and > or = 25% of total calories). Linear regression was used to estimate adjusted mean lipid levels. Logistic regression was used to determine adjusted odds ratios of dyslipidemia. Interactions between added sugars and sex were evaluated. Adjusted mean high-density lipoprotein cholesterol (HDL-C), geometric mean triglycerides, and mean low-density lipoprotein cholesterol (LDL-C) levels and adjusted odds ratios of dyslipidemia, including low HDL-C levels (< 40 mg/dL for men; < 50 mg/dL for women), high triglyceride levels (> or = 150 mg/dL), high LDL-C levels (> or = 130 mg/dL), or high ratio of triglycerides to HDL-C (> 3.8). Results were weighted to be representative of the US population. A mean of 15.8% of consumed calories was from added sugars. Among participants consuming less than 5%, 5% to less than 17.5%, 17.5% to less than 25%, and 25% or greater of total energy as added sugars, adjusted mean HDL-C levels were, respectively, 58.7, 57.5, 53.7, 51.0, and 47.7 mg/dL (P < .001 for linear trend), geometric mean triglyceride levels were 105, 102, 111, 113, and 114 mg/dL (P < .001 for linear trend), and LDL-C levels modified by sex were 116, 115, 118, 121, and 123 mg/dL among women (P = .047 for linear trend). There were no significant trends in LDL-C levels among men. Among higher consumers (> or = 10% added sugars) the odds of low HDL-C levels were 50% to more than 300% greater compared with the reference group (< 5% added sugars). In this study, there was a statistically significant correlation between dietary added sugars and blood lipid levels among US adults.

Ethnicity influences BMI as evaluated from reported serum lipid values in Inuit and non-Inuit: raised upper limit of BMI in Inuit?

PubMed

Noahsen, Paneeraq; Andersen, Stig

2013-01-01

To identify thresholds of BMI at which similar levels of serum lipids occur in Inuit and in non-Inuit as the impact of obesity on metabolic risk factors differ in Inuit compared to other ethnic groups. Published comparative data among Inuit and non-Inuit whites on BMI and HDL-cholesterol and triglyceride were identified for analysis. A literature search was done for BMI, lipids, Inuit and Greenland or Canada. Studies with data on triglycerides and HDL-cholesterol in Inuit and non-Inuit Caucasians were selected and data were retrieved. Regression equations were computed for BMI and HDL-cholesterol and BMI and triglycerides. BMI for similar levels of lipids in Inuit and non-Inuit and ratios of Inuit/non-Inuit BMI's were calculated. At BMI 25 kg/m2 HDL-cholesterol was 1.7/1.6 mM in Greenland Inuit/non-Inuit women and 1.7/1.5 mM in men in a major comparative study. HDL cholesterol decreased by 0.09 for each 1 kg/m2 increase in BMI. Serum triglycerides were 1.0/1.1 mM for Greenland Inuit/non-Inuit women and 0.9/ 1.4 mM for men at BMI 25 kg/m2. Slopes were around 0.1. A comparative study in Canadian Inuit/non-Inuit gave similar results. The BMI levels required for similar HDL-cholesterol or triglycerides were around 27.5 kg/m2, and Inuit/non-Inuit BMI-ratios were around 1.1. The same degree of dyslipidaemia was seen when Inuit had a 10% higher BMI compared to non-Inuit. This may support the establishment of Inuit-specific BMI cut-offs for the purposes of health screening and population health surveillance.

Omega-3 fatty acid therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation, however, did not significantly improve insulin sensitivity in patients with hypertriglyceridemia.

PubMed

Oh, Pyung Chun; Koh, Kwang Kon; Sakuma, Ichiro; Lim, Soo; Lee, Yonghee; Lee, Seungik; Lee, Kyounghoon; Han, Seung Hwan; Shin, Eak Kyun

2014-10-20

Experimental studies demonstrate that higher intake of omega-3 fatty acids (n-3 FA) improves insulin sensitivity, however, we reported that n-3 FA 2g therapy, most commonly used dosage did not significantly improve insulin sensitivity despite reducing triglycerides by 21% in patients. Therefore, we investigated the effects of different dosages of n-3 FA in patients with hypertriglyceridemia. This was a randomized, single-blind, placebo-controlled, parallel study. Age, sex, and body mass index were matched among groups. All patients were recommended to maintain a low fat diet. Forty-four patients (about 18 had metabolic syndrome/type 2 diabetes mellitus) in each group were given placebo, n-3 FA 1 (O1), 2 (O2), or 4 g (O4), respectively daily for 2 months. n-3 FA therapy dose-dependently and significantly decreased triglycerides and triglycerides/HDL cholesterol and improved flow-mediated dilation, compared with placebo (by ANOVA). However, each n-3 FA therapy did not significantly decrease high-sensitivity C-reactive protein and fibrinogen, compared with placebo. O1 significantly increased insulin levels and decreased insulin sensitivity (determined by QUICKI) and O2 significantly decreased plasma adiponectin levels relative to baseline measurements. Of note, when compared with placebo, each n-3 FA therapy did not significantly change insulin, glucose, adiponectin, glycated hemoglobin levels and insulin sensitivity (by ANOVA). We observed similar results in a subgroup of patients with the metabolic syndrome. n-3 FA therapy dose-dependently and significantly decreased triglycerides and improved flow-mediated dilation. Nonetheless, n-3 FA therapy did not significantly improve acute-phase reactants and insulin sensitivity in patients with hypertriglyceridemia, regardless of dosages. Copyright © 2014. Published by Elsevier Ireland Ltd.

[Reference values for cholesterol, triglycerides and glucose in a population of Hispanic children from 6 to 11 y, in the northern border of Mexico and the United States of America].

PubMed

Arenas Berumen, Ever; Gómez Miranda, Luis Mario; Torres Balcázar, Elías; Padilla Alvarado, Victor Hugo; Renteria, Ivan

2014-10-31

Overweight and obesity in children in the Mexico-USA border have evolved differently to the rest of their respective countries. New reference values of cholesterol, triglycerides and glucose are required to treatment. To determine the reference values of cholesterol, triglycerides and glucose in Hispanic children between 6 and 11 years in the Mexico-USA border. A prospective, cross-sectional, descriptive and observational study. A population of Hispanic children between 6 and 11 years of both boys and girls, belonging to three public institutions in the cities of Ensenada and Chihuahua, randomly selected, were studied. The study variables were the levels of total cholesterol (TC), triglycerides (TG) and glucose (G). From 300 subjects studied just 54 children completed the study. Higher average values of TC (168.7 ± 27.2 mg / dl), TG (80.6 ± 48.4 mg / dl) and G (88.3 ± 8.9 mg / dl) were observed. An additional behavior was founded, never reported previously to the limit of the knowledge of the authors; glucose levels of the children studied decreased with increased of cholesterol and triglycerides. To discard a random relationship between the variables, the Pearson correlation coefficient was determined between waist circumference and BMI, verifying an inverse association with G and direct with the TG. The reference values for Hispanic children between 6 and 11 years living on the northern border of Mexico-USA differ with respect to the national average values of the countries studied. Further studies are needed in larger populations to confirm the trend ob served in glucose levels of normal children, overweight and obese. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

The prevalence, risk factors and clinical correlates of obesity in Chinese patients with schizophrenia.

PubMed

Li, Qiongzhen; Du, Xiangdong; Zhang, Yingyang; Yin, Guangzhong; Zhang, Guangya; Walss-Bass, Consuelo; Quevedo, João; Soares, Jair C; Xia, Haishen; Li, Xiaosi; Zheng, Yingjun; Ning, Yuping; Zhang, Xiang Yang

2017-05-01

Obesity is a common comorbidity in schizophrenia. Few studies have addressed obesity in Chinese schizophrenia patients. The aims of this current study were to evaluate the prevalence, risk factors and clinical correlates of obesity in Chinese patients with schizophrenia. A total of 206 patients were recruited from a hospital in Beijing. Their clinical and anthropometric data together with plasma glucose and lipid parameters were collected. Positive and Negative Syndrome Scale (PANSS) was rated for all patients. Overall, 43 (20.9%) patients were obese and 67 (32.5%) were overweight. The obese patients had significantly higher glucose levels, triglyceride levels than non-obese patients. Females and patients with type 2 diabetes mellitus had increased risk for obesity. Correlation analysis showed that BMI was associated with sex, education levels, negative symptoms, total PANSS score, triglyceride levels and type 2 diabetes mellitus. Further stepwise regression analysis showed that sex, type 2 diabetes, education level, triglyceride and amount of smoking/day were significant predictors for obesity. Our study showed that the prevalence of obesity in Chinese patients with schizophrenia is higher than that in the general population. Some demographic and clinical variables are risk factors for obesity in schizophrenia. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Contemporary trends in dyslipidemia in the Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

Recent cross-sectional population studies in the United States have shown an increase in obesity, a decrease in cholesterol values, but no changes in levels of high-density lipoprotein cholesterol (HDL-C) or triglycerides (TG). Plasma total cholesterol, HDL-C, and TG levels, measured by the same met...

Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

USDA-ARS?s Scientific Manuscript database

Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

Loss-of-function mutations in APOC3, triglycerides, and coronary disease.

PubMed

Crosby, Jacy; Peloso, Gina M; Auer, Paul L; Crosslin, David R; Stitziel, Nathan O; Lange, Leslie A; Lu, Yingchang; Tang, Zheng-zheng; Zhang, He; Hindy, George; Masca, Nicholas; Stirrups, Kathleen; Kanoni, Stavroula; Do, Ron; Jun, Goo; Hu, Youna; Kang, Hyun Min; Xue, Chenyi; Goel, Anuj; Farrall, Martin; Duga, Stefano; Merlini, Pier Angelica; Asselta, Rosanna; Girelli, Domenico; Olivieri, Oliviero; Martinelli, Nicola; Yin, Wu; Reilly, Dermot; Speliotes, Elizabeth; Fox, Caroline S; Hveem, Kristian; Holmen, Oddgeir L; Nikpay, Majid; Farlow, Deborah N; Assimes, Themistocles L; Franceschini, Nora; Robinson, Jennifer; North, Kari E; Martin, Lisa W; DePristo, Mark; Gupta, Namrata; Escher, Stefan A; Jansson, Jan-Håkan; Van Zuydam, Natalie; Palmer, Colin N A; Wareham, Nicholas; Koch, Werner; Meitinger, Thomas; Peters, Annette; Lieb, Wolfgang; Erbel, Raimund; Konig, Inke R; Kruppa, Jochen; Degenhardt, Franziska; Gottesman, Omri; Bottinger, Erwin P; O'Donnell, Christopher J; Psaty, Bruce M; Ballantyne, Christie M; Abecasis, Goncalo; Ordovas, Jose M; Melander, Olle; Watkins, Hugh; Orho-Melander, Marju; Ardissino, Diego; Loos, Ruth J F; McPherson, Ruth; Willer, Cristen J; Erdmann, Jeanette; Hall, Alistair S; Samani, Nilesh J; Deloukas, Panos; Schunkert, Heribert; Wilson, James G; Kooperberg, Charles; Rich, Stephen S; Tracy, Russell P; Lin, Dan-Yu; Altshuler, David; Gabriel, Stacey; Nickerson, Deborah A; Jarvik, Gail P; Cupples, L Adrienne; Reiner, Alex P; Boerwinkle, Eric; Kathiresan, Sekar

2014-07-03

Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P=8×10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P=4×10(-6)). Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.).

Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease

PubMed Central

2014-01-01

Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G→A and IVS3+1G→T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1×10−20), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8×10−10). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4×10−6). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.) PMID:24941081

Efficient lowering of triglyceride levels in mice by human apoAV protein variants associated with hypertriglyceridemia.

PubMed

Vaessen, Stefan F C; Sierts, Jeroen A; Kuivenhoven, Jan Albert; Schaap, Frank G

2009-02-06

Variation in the apolipoprotein A5 (APOA5) gene has consistently been associated with increased plasma triglyceride (TG) levels in epidemiological studies. In vivo functionality of these variations, however, has thus far not been tested. Using adenoviral over-expression, we evaluated plasma expression levels and TG-lowering efficacies of wild-type human apoAV, two human apoAV variants associated with increased TG (S19W, G185C) and one variant (Q341H) that is predicted to have altered protein function. Injection of mice with adenovirus encoding wild-type or mutant apoAV resulted in an identical dose-dependent elevation of human apoAV levels in plasma. The increase in apoAV levels resulted in pronounced lowering of plasma TG levels at two viral dosages. Unexpectedly, the TG-lowering efficacy of all three apoAV variants was similar to wild-type apoAV. In addition, no effect on TG-hydrolysis-related plasma parameters (free fatty acids, glycerol and post-heparin lipoprotein lipase activity) was apparent upon expression of all apoAV variants. In conclusion, our data indicate that despite their association with hypertriglyceridemia and/or predicted protein dysfunction, the 19W, 185C and 341H apoAV variants are equally effective in reducing plasma TG levels in mice.

Familial hypertriglyceridemia

MedlinePlus

The goal of treatment is to control conditions that can raise triglyceride levels. These include obesity , hypothyroidism , and diabetes . Your provider may tell you not to drink alcohol. Certain birth control pills can raise triglyceride levels. ...

Factors Affecting Hypertension among the Malaysian Elderly

PubMed Central

Eshkoor, Sima Ataollahi; Hamid, Tengku Aizan; Shahar, Suzana; Ng, Chee Kyun; Mun, Chan Yoke

2016-01-01

Hypertension is a common chronic disease in the elderly. This study aimed to determine the effects of age, ethnicity, gender, education, marital status, nutritional parameters, and blood elements on the risk of high blood pressure in the Malaysian elderly. This research was conducted on a group of 2322 non-institutionalized Malaysian elderly. The hierarchy binary logistic regression analysis was applied to estimate the risk of hypertension in respondents. Approximately, 45.61% of subjects had hypertension. The findings indicated that the female gender (Odds ratio (OR) = 1.54), an increase in body weight (OR = 1.61), and an increase in the blood levels of albumin (OR = 1.51), glucose (OR = 1.92), and triglycerides (OR = 1.27) significantly increased the risk of hypertension in subjects (p < 0.05). Conversely, an increase in both dietary carbohydrates (OR = 0.74), and blood cholesterol level (OR = 0.42) significantly reduced the risk of hypertension in samples (p < 0.05). Furthermore, the results showed that ethnicity was a non-relevant factor to increase the risk of hypertension in subjects. It was concluded that female gender, an increase in body weight, and an increase in the blood levels of glucose, triglycerides, and albumin enhanced the risk of high blood pressure in the Malaysian elderly. In addition, an increase in both dietary carbohydrates and blood cholesterol level decreased hypertension in subjects. PMID:29367559

N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats.

PubMed

Onopchenko, Oleksandra V; Kosiakova, Galina V; Oz, Murat; Klimashevsky, Vitaliy M; Gula, Nadiya M

2015-01-01

This study investigates the protective effect of N-stearoylethanolamine (NSE), a bioactive N-acylethanolamine , on the lipid profile distribution in the pancreas of obesity-induced insulin resistant (IR) rats fed with prolonged high fat diet (58% of fat for 6 months). The phospholipid composition was determined using 2D thin-layer chromatography. The level of individual phospholipids was estimated by measuring inorganic phosphorus content. The fatty acid (FA) composition and cholesterol level were investigated by gas-liquid chromatography. Compared to controls, plasma levels of triglycerides and insulin were significantly increased in IR rats. The pancreas lipid composition indicated a significant reduction of the free cholesterol level and some phospholipids such as phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) compared to controls. Moreover, the FA composition of pancreas showed a significant redistribution of the main FA (18:1n-9, 18:2n-6, 18:3n-6 and 20:4n-6) levels between phospholipid, free FA, triglyceride fractions under IR conditions that was accompanied by a change in the estimated activities of Δ9-, Δ6-, Δ5-desaturase. Administration of N-stearoylethanolamine (NSE, 50 mg/kg daily per os for 2 weeks) IR rats triggered an increase in the content of free cholesterol, PtdCho and normalization of PtdEtn, PtdSer level. Furthermore, the NSE modulated the activity of desaturases, thus influenced FA composition and restored the FA ratios in the lipid fractions. These NSE-induced changes were associated with a normalization of plasma triglyceride content, considerable decrease of insulin and index HOMA-IR level in rats under IR conditions.

The independent relationship between triglycerides and coronary heart disease.

PubMed

Morrison, Alan; Hokanson, John E

2009-01-01

The aim was to review epidemiologic studies to reassess whether serum levels of triglycerides should be considered independently of high-density lipoprotein-cholesterol (HDL-C) as a predictor of coronary heart disease (CHD). We systematically reviewed population-based cohort studies in which baseline serum levels of triglycerides and HDL-C were included as explanatory variables in multivariate analyses with the development of CHD (coronary events or coronary death) as dependent variable. A total of 32 unique reports describing 38 cohorts were included. The independent association between elevated triglycerides and risk of CHD was statistically significant in 16 of 30 populations without pre-existing CHD. Among populations with diabetes mellitus or pre-existing CHD, or the elderly, triglycerides were not significantly independently associated with CHD in any of 8 cohorts. Triglycerides and HDL-C were mutually exclusive predictors of coronary events in 12 of 20 analyses of patients without pre-existing CHD. Epidemiologic studies provide evidence of an association between triglycerides and the development of primary CHD independently of HDL-C. Evidence of an inverse relationship between triglycerides and HDL-C suggests that both should be considered in CHD risk estimation and as targets for intervention.

The independent relationship between triglycerides and coronary heart disease

PubMed Central

Morrison, Alan; Hokanson, John E

2009-01-01

Aims: The aim was to review epidemiologic studies to reassess whether serum levels of triglycerides should be considered independently of high-density lipoprotein-cholesterol (HDL-C) as a predictor of coronary heart disease (CHD). Methods and results: We systematically reviewed population-based cohort studies in which baseline serum levels of triglycerides and HDL-C were included as explanatory variables in multivariate analyses with the development of CHD (coronary events or coronary death) as dependent variable. A total of 32 unique reports describing 38 cohorts were included. The independent association between elevated triglycerides and risk of CHD was statistically significant in 16 of 30 populations without pre-existing CHD. Among populations with diabetes mellitus or pre-existing CHD, or the elderly, triglycerides were not significantly independently associated with CHD in any of 8 cohorts. Triglycerides and HDL-C were mutually exclusive predictors of coronary events in 12 of 20 analyses of patients without pre-existing CHD. Conclusions: Epidemiologic studies provide evidence of an association between triglycerides and the development of primary CHD independently of HDL-C. Evidence of an inverse relationship between triglycerides and HDL-C suggests that both should be considered in CHD risk estimation and as targets for intervention. PMID:19436658

The gut microbiota modulates host energy and lipid metabolism in mice[S

PubMed Central

Velagapudi, Vidya R.; Hezaveh, Rahil; Reigstad, Christopher S.; Gopalacharyulu, Peddinti; Yetukuri, Laxman; Islam, Sama; Felin, Jenny; Perkins, Rosie; Borén, Jan; Orešič, Matej; Bäckhed, Fredrik

2010-01-01

The gut microbiota has recently been identified as an environmental factor that may promote metabolic diseases. To investigate the effect of gut microbiota on host energy and lipid metabolism, we compared the serum metabolome and the lipidomes of serum, adipose tissue, and liver of conventionally raised (CONV-R) and germ-free mice. The serum metabolome of CONV-R mice was characterized by increased levels of energy metabolites, e.g., pyruvic acid, citric acid, fumaric acid, and malic acid, while levels of cholesterol and fatty acids were reduced. We also showed that the microbiota modified a number of lipid species in the serum, adipose tissue, and liver, with its greatest effect on triglyceride and phosphatidylcholine species. Triglyceride levels were lower in serum but higher in adipose tissue and liver of CONV-R mice, consistent with increased lipid clearance. Our findings show that the gut microbiota affects both host energy and lipid metabolism and highlights its role in the development of metabolic diseases. PMID:20040631

Effects of eicosapentaenoic acid on hepatic dyslipidemia and oxidative stress in high fat diet-induced steatosis.

PubMed

Hirotani, Yoshihiko; Ozaki, Nozomi; Tsuji, Yoshihiro; Urashima, Yoko; Myotoku, Michiaki

2015-01-01

We investigated the ability of eicosapentaenoic acid (EPA) to prevent high-fat diet (HFD)-induced obesity and non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed standard chow (5.3% fat content), an HFD (32.0% fat content) or an HFD + EPA (1 g/kg/day EPA for the last 6 weeks) for 12 weeks. Serum total cholesterol, hepatic triglyceride and total cholesterol levels were significantly increased in the HFD group, in comparison with those of normal mice (p < 0.01). In contrast, hepatic triglyceride and total cholesterol levels were significantly decreased in the HFD + EPA group, in comparison with those of the HFD group (p < 0.05). In addition, EPA decreased the body weight of obese mice and improved hepatic function. Hepatic superoxide dismutase activity and glutathione levels were significantly decreased in obese mice, but increased with EPA administration. Our data suggest that EPA supplementation has a beneficial effect on NAFLD progression.

[Effect of decamethoxine, decamine and levorin on the content of cholesterol, phospholipids and triglycerides in albino rat liver].

PubMed

Kovtuniak, N A; Bordiakovskaia, L G; Stadniĭchuk, R F

1983-01-01

It has been shown in experiments that intramuscular injection of guaternary ammonium compounds (decamethoxine and decamine) and levorin changed the content of cholesterol, phospholipids and triglycerides in the liver of white rats. Decamethoxine decreased the content of phospholipids and cholesterol and raised the concentration of triglycerides. Decamine decreased the level of phospholipids and raised the content of cholesterol and triglycerides, while levorin minimized the content of phospholipids, cholesterol and triglycerides.

Increased IL18 mRNA levels in peripheral artery disease and its association with triglyceride and LDL cholesterol levels: a pilot study.

PubMed

Deser, Serkan Burc; Bayoglu, Burcu; Besirli, Kazım; Cengiz, Mujgan; Arapi, Berk; Junusbekov, Yerik; Dirican, Ahmet; Arslan, Caner

2016-06-01

Peripheral artery disease (PAD) typically refers to lower limb vessel ischemia caused by atherosclerotic stenosis of lower extremity arteries. IL18 is a pleiotropic pro-inflammatory cytokine reported to function as an inflammatory biomarker in cardiovascular diseases. IL18 activity is balanced by high-affinity naturally occurring IL18-binding protein (IL18BP). This study aimed to determine whether IL18, IL18 BP mRNA levels and -137 G/C (rs187238) polymorphism, which was previously associated with IL18 gene transcriptional activity, were associated with PAD etiology. IL18, IL18BP mRNA levels from peripheral blood mononuclear cells and -137 G/C (rs187238) polymorphism were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and RT-PCR, respectively, in 55 PAD patients (26 aorta-iliac, 29 femoro-popliteal) and 61 disease-free controls. IL18 mRNA levels were increased in PAD patients compared with healthy controls (p = 0.09); however, did not reach a statistical significant level, also did not significantly differ between aorta-iliac and femoro-popliteal occlusive PAD subgroups (p = 0.285). However, IL18BP mRNA levels were significantly lower in PAD group compared with controls (p < 0.001). Genotype frequencies of rs187238 polymorphism did not significantly differ between PAD patients and controls (p = 0.385). IL18 mRNA levels were significantly correlated with triglycerides and LDL cholesterol levels in PAD patients (p = 0.003, p = 0.014, respectively). HDL cholesterol levels were negatively correlated with IL18 mRNA levels in controls (p = 0.05). This report is a preliminary study to show an association between IL18, IL18BP mRNA levels and PAD and suggests that the IL18 gene may have a significant relationship with triglyceride and LDL cholesterol levels in PAD patients.

Consumption of whole grains and legumes modulates the genetic effect of the APOA5 -1131C variant on changes in triglyceride and apolipoprotein A-V concentrations in patients with impaired fasting glucose or newly diagnosed type 2 diabetes.

PubMed

Kang, Ryungwoo; Kim, Minjoo; Chae, Jey Sook; Lee, Sang-Hyun; Lee, Jong Ho

2014-04-01

The apolipoprotein A5 gene (APOA5) -1131 T > C polymorphism is associated with mild hypertriglyceridemia in type 2 diabetic subjects, and interacts with dietary fat in the determination of triglyceride concentrations. We examined whether a substitution of whole grains and legumes for refined rice in a high carbohydrate diet (about 65% of energy derived from carbohydrate) may modify the effect of this variant on changes in apolipoprotein A-V (apoA-V) and triglyceride concentrations. We genotyped the APOA5 -1131 T > C in individuals with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes, who were randomly assigned to either a group ingesting whole grain and legume meals daily or a control group for 12 weeks. After dietary intervention, we observed significant interactions between the APOA5 -1131 T > C polymorphism and carbohydrate sources (whole grains and legumes versus refined rice) in the determination of mean percent changes in triglyceride and apoA-V (P interactions <0.001 and =0.038, respectively). In the refined rice group (n = 93), the carriers of the risk C allele (n = 50) showed a greater increase in the mean percent changes of triglyceride and apoA-V than noncarriers after adjusting for HOMA-IR (P = 0.004 and 0.021, respectively). The whole grain and legume group (n = 92), however, showed a decrease in fasting glucose, HOMA-IR, and triglyceride, and an increase in apoA-V, irrespective of genotype. The data showed that the magnitude of the genetic effect of the APOA5 -1131C variant on triglyceride and apoA-V levels was modulated when substituting consumption of whole grains and legumes for refined rice as a carbohydrate source in IFG or diabetic subjects. ClinicalTrials.gov: NCT01784952.

Normal fasting plasma glucose levels and type 2 diabetes in young men.

PubMed

Tirosh, Amir; Shai, Iris; Tekes-Manova, Dorit; Israeli, Eran; Pereg, David; Shochat, Tzippora; Kochba, Ilan; Rudich, Assaf

2005-10-06

The normal fasting plasma glucose level was recently defined as less than 100 mg per deciliter (5.55 mmol per liter). Whether higher fasting plasma glucose levels within this range independently predict type 2 diabetes in young adults is unclear. We obtained blood measurements, data from physical examinations, and medical and lifestyle information from men in the Israel Defense Forces who were 26 to 45 years of age. A total of 208 incident cases of type 2 diabetes occurred during 74,309 person-years of follow-up (from 1992 through 2004) among 13,163 subjects who had baseline fasting plasma glucose levels of less than 100 mg per deciliter. A multivariate model, adjusted for age, family history of diabetes, body-mass index, physical-activity level, smoking status, and serum triglyceride levels, revealed a progressively increased risk of type 2 diabetes in men with fasting plasma glucose levels of 87 mg per deciliter (4.83 mmol per liter) or more, as compared with those whose levels were in the bottom quintile (less than 81 mg per deciliter [4.5 mmol per liter], P for trend <0.001). In multivariate models, men with serum triglyceride levels of 150 mg per deciliter (1.69 mmol per liter) or more, combined with fasting plasma glucose levels of 91 to 99 mg per deciliter (5.05 to 5.50 mmol per liter), had a hazard ratio of 8.23 (95 percent confidence interval, 3.6 to 19.0) for diabetes, as compared with men with a combined triglyceride level of less than 150 mg per deciliter and fasting glucose levels of less than 86 mg per deciliter (4.77 mmol per liter). The joint effect of a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or more and a fasting plasma glucose level of 91 to 99 mg per deciliter resulted in a hazard ratio of 8.29 (95 percent confidence interval, 3.8 to 17.8), as compared with a body-mass index of less than 25 and a fasting plasma glucose level of less than 86 mg per deciliter. Higher fasting plasma glucose levels within the normoglycemic range constitute an independent risk factor for type 2 diabetes among young men, and such levels may help, along with body-mass index and triglyceride levels, to identify apparently healthy men at increased risk for diabetes. Copyright 2005 Massachusetts Medical Society.

Blood cadmium concentration and lipid profile in Korean adults

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

Kim, Kisok, E-mail: kimkisok@kmu.ac.kr

Although animal experiments have shown that cadmium exposure induces alterations in lipid profiles, no epidemiological study of this relationship has been performed. The objective of this study was to evaluate the association between blood cadmium concentration and blood lipid levels in Korean adults. A cross-sectional study comprising participants (n=3903) aged 20 years or older from the 2005, 2008, and 2009 Korea National Health and Nutrition Examination Surveys was conducted. Demographic characteristics and dietary intake were obtained from the participants by questionnaire, and cadmium and lipid levels were determined by analysis of blood samples. After adjusting for demographic and dietary factors,more » blood concentration of cadmium was positively associated with the risk of low high-density lipoprotein cholesterol (HDL-C) in a dose-dependent manner (p for trend <0.001). In addition, the odds ratios (ORs) of a high triglyceride to HDL-C ratio was significantly increased in the high blood cadmium groups [OR=1.36; 95% confidence interval (CI), 1.03-1.79 for fourth quintile and OR=1.41; 95% CI, 1.07-1.86 for fifth quintile] compared with the lowest quintile group. However, high blood cadmium was not associated with a risk of high total cholesterol, high low-density lipoprotein cholesterol, or high triglycerides. These data suggest that an increased cadmium body burden increases the risk of dyslipidemia, mainly due to the increased risk of low HDL-C and the high ratio of triglycerides to HDL-C.« less

High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels

PubMed Central

Bocarsly, Miriam E.; Powell, Elyse S.; Avena, Nicole M.; Hoebel, Bartley G.

2010-01-01

High-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Some studies have shown that short-term access to HFCS can cause increased body weight, but the findings are mixed. The current study examined both short- and long-term effects of HFCS on body weight, body fat, and circulating triglycerides. In Experiment 1, male Sprague-Dawley rats were maintained for short term (8 wks) on (1) 12-h/day of 8% HFCS, (2) 12-h/day 10% sucrose, (3) 24-h/day HFCS, all with ad libitum rodent chow, or (4) ad libitum chow alone. Rats with 12-h access to HFCS gained significantly more body weight than animals given equal access to 10% sucrose, even though they consumed the same number of total calories but fewer calories from HFCS than sucrose. In Experiment 2, the long-term effects of HFCS on body weight and obesogenic parameters, as well as gender differences, were explored. Over the course of 6 or 7 months, both male and female rats with access to HFCS gained significantly more body weight than control groups. This increase in body weight with HFCS was accompanied by an increase in adipose fat, notably in the abdominal region, and elevated circulating triglyceride levels. Translated to humans, these results suggest that excessive consumption of HFCS may contribute to the incidence of obesity. PMID:20219526

High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels.

PubMed

Bocarsly, Miriam E; Powell, Elyse S; Avena, Nicole M; Hoebel, Bartley G

2010-11-01

High-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Some studies have shown that short-term access to HFCS can cause increased body weight, but the findings are mixed. The current study examined both short- and long-term effects of HFCS on body weight, body fat, and circulating triglycerides. In Experiment 1, male Sprague-Dawley rats were maintained for short term (8 weeks) on (1) 12 h/day of 8% HFCS, (2) 12 h/day 10% sucrose, (3) 24 h/day HFCS, all with ad libitum rodent chow, or (4) ad libitum chow alone. Rats with 12-h access to HFCS gained significantly more body weight than animals given equal access to 10% sucrose, even though they consumed the same number of total calories, but fewer calories from HFCS than sucrose. In Experiment 2, the long-term effects of HFCS on body weight and obesogenic parameters, as well as gender differences, were explored. Over the course of 6 or 7 months, both male and female rats with access to HFCS gained significantly more body weight than control groups. This increase in body weight with HFCS was accompanied by an increase in adipose fat, notably in the abdominal region, and elevated circulating triglyceride levels. Translated to humans, these results suggest that excessive consumption of HFCS may contribute to the incidence of obesity. Copyright © 2010 Elsevier Inc. All rights reserved.

Protective effects of azelaic acid against high-fat diet-induced oxidative stress in liver, kidney and heart of C57BL/6J mice.

PubMed

Muthulakshmi, Shanmugam; Saravanan, Ramalingam

2013-05-01

Excess fat intake induces hyperinsulinaemia, increases nutrient uptake and lipid accumulation, amplifies ROS generation, establishes oxidative stress and morphological changes leading to tissue injury in the liver, kidney and heart of high-fat diet (HFD)-fed mice. The effect of azelaic acid (AzA), a C9 α,ω-dicarboxylic acid, against HFD-induced oxidative stress was investigated by assaying the activities and levels of antioxidants and oxidative stress markers in the liver, kidney and heart of C57BL/6J mice. Mice were segregated into two groups, one fed standard diet (NC) and the other fed high-fat diet (HFD) for 15 weeks. HFD-fed mice were subjected to intragastric administration of AzA (80 mg/kg BW)/RSG (10 mg/kg BW) during 11-15 weeks. Glucose, insulin, triglycerides, hepatic and nephritic markers were analysed in the plasma and the activity of enzymatic, non-enzymatic antioxidants and lipid peroxidation markers were examined in the plasma/erythrocytes, liver, kidney and heart of normal and experimental mice. We inferred significant decrease in enzymatic and non-enzymatic antioxidants along with significant increase in glucose, insulin, hepatic and nephritic markers, triglycerides and lipid peroxidation markers in HFD-fed mice. Administration of AzA could positively restore the levels of plasma glucose, insulin, triglycerides, hepatic and nephritic markers to near normal. AzA increased the levels of enzymatic and nonenzymatic antioxidants with significant reduction in the levels of lipid peroxidation markers. Histopathological examination of liver, kidney and heart substantiated these results. Hence, we put forward that AzA could counteract the potential injurious effects of HFD-induced oxidative stress in C57BL/6J mice.

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

Increased Cardiovascular Risk Using Atherogenic Index Measurement Among Healthcare Workers.

PubMed

Juárez-Pérez, Cuauhtémoc Arturo; Aguilar-Madrid, Guadalupe; Haro-García, Luis Cuauhtémoc; Gopar-Nieto, Rodrigo; Cabello-López, Alejandro; Jiménez-Ramírez, Carmina; Aguado, Aida; Martínez-Méndez, Luz María; Chávez-Negrete, Adolfo

2015-04-01

Cardiovascular diseases are one of the leading causes of death worldwide. This burden of disease is particularly high among healthcare workers. The aim of the study was to identify determinants that increase atherogenic index among healthcare workers. In 1,678 healthcare workers, cardiovascular risk factors were analyzed: body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Atherogenic index was calculated and determinants were identified. Mean (SD) age was 41.2 (8.4) years; body mass index 28.4 (4.8); waist-hip-ratio 0.88 (0.07); glucose 96.6 (22.2) μg/dL; TC 195.3 (50.3) mg/dL; HDL 49.0 (16.3) mg/dL; LDL 112.7 (35.0) mg/dL; triglycerides 171.7 (121.2) mg/dL; and atherogenic index 3.3 (1.5). Overweight and obesity prevalence was 77.2%. In the multiple linear regression model, the coefficients for AI were being a physician β = 0.381, male gender = 0.443, BMI β = 0.35, waist-to-hip ratio β = 2.15, age = 0.014, and triglycerides β = 0.915. The main contributors to atherogenic index increase were male sex, increased age, waist-to-hip ratio increase, overweight and obesity, high triglyceride levels and working as a physician. Although waist-to-hip ratio was the most powerful determinant, the physician occupational category added risk factors such as stress and adverse psychosocial working conditions, which may potentiate cardiovascular diseases. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Determinants of Blood Cell Omega-3 Fatty Acid Content

PubMed Central

Block, Robert C.; Harris, William S.; Pottala, James V.

2009-01-01

Background Although red blood cell eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) content (the Omega-3 Index) predicts cardiovascular death, the factors determining the Index are unknown. Methods In 704 outpatients, we undertook an investigation of the clinical determinants of the Index. Results Factors associated with the Index in decreasing order were: EPA+DHA supplement use, fish consumption frequency, triglyceride level, age, high cholesterol history, and smoking. These factors explained 59% of Index variability, with capsules/fish intake together accounting for 47%. The Index increased by 13% (p< 0.0001) for each serving level increase in fish intake and EPA+DHA supplementation correlated with a 58% increase (p< 0.0001) regardless of background fish intake (p=0.25; test for interaction). A 100 mg/dL decrease in serum triglycerides was associated with a 15% higher (p<0.0001) Index. Conclusions The intake of EPA+DHA-rich foods and supplements principally determined the Omega-3 Index, but explained only about half of the variability. PMID:19953197

Optimal energy distribution of carbohydrate intake for Japanese elderly patients with type 2 diabetes: the Japanese Elderly Intervention Trial.

PubMed

Kamada, Chiemi; Yoshimura, Hidenori; Okumura, Ryota; Takahashi, Keiko; Iimuro, Satoshi; Ohashi, Yasuo; Araki, Atsushi; Umegaki, Hiroyuki; Sakurai, Takashi; Yoshimura, Yukio; Ito, Hideki

2012-04-01

In diet therapy for diabetes, optimal energy intake and the energy distribution of macronutrients (protein : fat : carbohydrate [PFC] energy ratio) are important. We aimed to clarify the correlation between the PFC energy ratio and metabolic parameters including glycated hemoglobin A1c (HbA1c) and triglycerides in Japanese elderly patients with type 2 diabetes mellitus aged 65 years or older. Participants were 1173 diabetic patients aged 65 years or older with serum HbA1c level of >/=7.4% enrolled in the Japanese Elderly Diabetes Intervention Trial (J-EDIT). The participants were divided into four groups by the percentage of total energy intake (%E) of carbohydrate (C1: less than 55%E, C2: 55%E or more and less than 60%E, C3: 60%E or more and less than 65%E, and C4: 65%E or more). Relations of %E of carbohydrate to HbA1c and other metabolic parameters, energy intake and nutritional intake were examined. Furthermore, the subjects were divided into four categories by HbA1c levels by quartile method (Q1: less than 7.90%, Q2: 7.90% or more and less than 8.30%, Q3: 8.30% or more and less than 8.80%, Q4: 8.80% or more). Relations of HbA1c to other metabolic parameters, energy intake and nutritional intake were examined. The mean HbA1c levels in the four groups were C1: 8.40%, C2: 8.50%, C3: 8.41% and C4: 8.36% in men, and C1: 8.51%, C2: 8.47%, C3: 8.35% and C4: 8.52% in women, respectively. There were no significant differences and linear trend in HbA1c levels across groups. The mean triglyceride levels were in the range of 122-128 mg/dL in men from C1 to C3, although it was significantly higher in C4 (177 mg/dL). The mean triglyceride levels were in the range of 128-136 mg/dL in women from C1 to C3, although it was significantly higher in Q4 (150 mg/dL). Amounts of protein and fat intakes decreased with an increase of %E of carbohydrate, although amount of carbohydrate intake did not change significantly. As a result, %E of protein and fat, and energy intake decreased in both men and women with an increase in %E of carbohydrate. Among the four quartiles divided by HbA1c levels, there were no significant differences in energy intake and PFC energy ratio. The present study suggests that, within the range studied, the carbohydrate energy ratio has no correlation with HbA1c levels. However, serum triglyceride levels increased and high-density lipoprotein cholesterol levels decreased significantly, with an increase of %E of carbohydrate in men, and the same tendencies were observed in women. Furthermore, in patients with 65%E or more of carbohydrate, serum triglyceride levels exceeded 150 mg/dL, which is the recommended treatment target for diabetic patients. These results suggest that the ideal %E of carbohydrate for Japanese elderly type 2 diabetes is less than 65. The lower limit of %E of carbohydrate could not be determined from the present study. © 2012 Japan Geriatrics Society.

Uric acid and obesity-related phenotypes in postmenopausal women.

PubMed

Grygiel-Górniak, B; Mosor, M; Marcinkowska, J; Przysławski, J; Nowak, J

2018-06-01

The aim of this study was to find the genetic, metabolic, and nutritional risk factors, which can be associated with uric acid (UA) level. The risk factors related to uricemia were assessed among 271 postmenopausal women without cardiometabolic disorders and hypolipidemic/hypoglycemic treatment selected from a cohort of 1423 obese postmenopausal women. The bioimpedance analysis and biochemical and genetic analyses were performed in two groups characterized by serum UA ≥ 4 mg/dL (238 μmol/L) and < 4 mg/dL. The TaqMan-based real-time PCR method was applied to assess the role of Pro12Ala of peroxisome proliferation-activated receptor (PPAR)gamma-2 and Trp64Arg of beta-3-adrenergic receptor (ADRB) polymorphisms. Women with UA level ≥ 4 mg/dL were characterized by larger body mass, triceps skinfold, waist circumference, body fat amount, and serum insulin, glucose, and triglyceride levels. There was no difference in dietary habits between the analyzed groups. Body mass, waist circumference, body fat amount, diastolic blood pressure, and serum insulin, glucose, high-density lipoprotein, and triglyceride levels, Homeostasis Model Assessment-Insulin Resistance, and energy from the dietary fat influence the UA level ≥ 4 mg/dL; however, the serum UA was not determined by Pro12Ala and Trp64Arg polymorphism analyses. The model of linear regression revealed that the group characterized by body mass index  ≥ 25 kg/m 2 and glucose ≥ 100 mg/dL has 4 times increased risk of UA level (p = 0.0009); after adding triglycerides ≥ 150 mg/dL, the risk of UA increased 7 times (p = 0.0216). Increasing the level of UA ≥ 4 mg/dL is associated with overweight, hyperglycemia, and hypertriglyceridemia in women without a history of cardiometabolic disorders. A better management of metabolic factors could help prevent further increase in UA levels.

Insulin sensitivity is related to fat oxidation and protein kinase C activity in children with acute burn injury

PubMed Central

Cree, Melanie G.; Zwetsloot, Jennifer J.; Herndon, David N.; Newcomer, Bradley R.; Fram, Ricki Y.; Angel, Carlos; Green, Justin M.; Dohm, Gerald L.; Sun, Dayoung; Aarsland, Asle; Wolfe, Robert R.

2014-01-01

Objective Impaired fatty acid oxidation occurs with type 2 diabetes and is associated with accumulations of intracellular lipids, which may increase diacylglycerol, stimulate protein kinase C activity and inactivate insulin signaling. Glucose and fat metabolism are altered in burn patients, but have never been related to intracellular lipids or insulin signaling. Methods Thirty children sustaining >40% total body surface area burns were studied acutely with glucose and palmitate tracer infusions and a hyper-insulinemic euglycemic clamp. Muscle triglyceride, diacylglycerol, fatty acyl CoA and insulin signaling were measured. Liver and muscle triglyceride levels were measured with magnetic resonance spectroscopy. Muscle samples from healthy children were controls for diacylglycerol concentrations. Results Insulin sensitivity was reduced and correlated with whole body palmitate β-oxidation (P=0.004). Muscle insulin signaling was not stimulated by hyper-insulinemia. Tissue triglyceride concentrations and activated protein kinase C-β were elevated, whereas the concentration of diacylglycerol was similar to the controls. Free fatty acid profiles of muscle triglyceride did not match diacylglycerol. Conclusions Insulin resistance following burn injury is accompanied by decreased insulin signaling and increased protein kinase C-β activation. The best metabolic predictor of insulin resistance in burned patients was palmitate oxidation. PMID:18535477

Rescue of cardiac leptin receptors in db/db mice prevents myocardial triglyceride accumulation.

PubMed

Hall, Michael E; Maready, Matthew W; Hall, John E; Stec, David E

2014-08-01

Increased leptin levels have been suggested to contribute to cardiac hypertrophy and attenuate cardiac lipid accumulation in obesity, although it has been difficult to separate leptin's direct effects from those caused by changes in body weight and adiposity. To determine whether leptin attenuates cardiac lipid accumulation in obesity or directly causes left ventricular hypertrophy (LVH), we generated a novel mouse model in which the long form of the leptin receptor (LepR) was "rescued" only in cardiomyocytes of obese db/db mice. Reexpression of cardiomyocyte leptin receptors in db/db mice did not cause LVH but reduced cardiac triglycerides and improved cardiac function. Compared with lean wild-type (WT) or db/db-cardiac LepR rescue mice, db/db mice exhibited significantly lower E/A ratio, a measurement of early to late diastolic filling, which averaged 1.5 ± 0.07 in db/db vs. 1.9 ± 0.08 and 1.8 ± 0.11 in WT and db/db-cardiac LepR rescue mice, respectively. No differences in systolic function were observed. Although db/db and db/db-cardiac LepR rescue mice exhibited similar increases in plasma triglycerides, insulin, glucose, and body weight, cardiac triglycerides were significantly higher in db/db compared with WT and db/db cardiac LepR rescue mice, averaging 13.4 ± 4.2 vs. 3.8 ± 1.6 vs. 3.8 ± 0.7 mg/g, respectively. These results demonstrate that despite significant obesity and increases in plasma glucose and triglycerides, db/db cardiac LepR rescue mice are protected against myocardial lipid accumulation. However, we found no evidence that leptin directly causes LVH. Copyright © 2014 the American Physiological Society.

Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

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

Li, Jing; Luo, Hanwen; Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071

Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected.more » Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine metabolic dysfunction than male. • There were interactions among caffeine, high-fat diet and gender.« less

ACE, APOA5, and MTP Gene Polymorphisms Analysis in Relation to Triglyceride and Insulin Levels in Pediatric Patients.

PubMed

Carranza-González, Lilia; León-Cachón, Rafael B R; González-Zavala, María Antonia; Ríos-Ibarra, Clara; Morlett-Chávez, Jesús; Sánchez-Domínguez, Celia; Cepeda-Nieto, Ana; Salinas-Santander, Mauricio

2018-04-25

Obesity is a complex, chronic, and multifactorial disease that has become a major, and worldwide, public health problem contributing to an increased number of pathologies, including type 2 diabetes, cardiovascular disease, hyperlipidemia, and metabolic syndrome, thus suggesting a commolon origin. A diet high in sugar and fats coupled with a sedentary lifestyle has a major role in the development of obesity. However, the genetic background has also been associated with body fat accumulation. The aim of this study was to assess the effect ofACE-rs4646994, APOA5-rs662799, and MTP-rs1800591 gene polymorphisms on clinical and biochemical parameters and to evaluate the association with body phenotypes in children and adolescent population of Saltillo, Coahuila, Mexico. Anthropometric, clinical, biochemical parameters and BMI were obtained from 405 children and adolescents. The BMI was used to determine the body phenotype. The rs4646994 gene polymorphism was determined by PCR, whereas rs662799 and rs1800591 were determined by PCR-RFLP. The obtained results were analyzed to determine their association of these single nucleotide polymorphisms with body phenotype and biochemical parameters. TT genotype for APOA5-rs662799 was associated with increased levels of HDL-C in the analyzed population (p <0.05). The ACErs4646994gene polymorphism is associated with high Insulin levels, HOMAIR index, and triglyceride levels, mainly when presenting a I/I genotype (p <0.05). The polymorphic allele of the ACE gene is capable of modulating triglyceride levels, insulin levels and HOMA-IR index in the evaluated population; it must be highlighted that this has not been reported in other studied populations elsewhere. Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.

Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature.

PubMed

Ito, Matthew K

2015-10-01

Hypertriglyceridemia affects approximately 33% of the US population. Elevated triglyceride levels are independently associated with cardiovascular disease (CVD) risk, and severe hypertriglyceridemia is a risk factor for acute pancreatitis. Guidelines for the management of severe hypertriglyceridemia (≥5.6 mmol/L [≥500 mg/dL]) recommend immediate use of triglyceride-lowering agents; however, statins remain the first line of therapy for the management of mild to moderate hypertriglyceridemia (1.7-5.6 mmol/L [150-499 mg/dL]). Statins primarily target elevated low-density lipoprotein cholesterol levels, but have also been shown to reduce mean triglyceride levels by up to 18% (or 43% in patients with triglyceride levels≥3.1 mmol/L [≥273 mg/dL]). However, individuals with hypertriglyceridemia may need additional reduction in triglyceride-rich lipoproteins and remnant particles to further reduce residual CVD risk. A number of guidelines recommend the addition of fibrates, niacin, or long-chain omega-3 fatty acids if elevated triglyceride or non-high-density lipoprotein cholesterol levels persist despite the use of high-intensity statin therapy. This review evaluates the impact of fibrates, niacin, and long-chain omega-3 fatty acids on lipid profiles and cardiovascular outcomes in patients with hypertriglyceridemia. It also assesses the adverse effects and drug-drug interactions associated with these triglyceride-lowering agents, because although they have all been shown to effectively reduce triglyceride levels in patients with hypertriglyceridemia, they differ with regard to their associated benefit-risk profiles. Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin, yet further large-scale clinical studies are required to evaluate their effects on cardiovascular outcomes and CVD risk reduction in patients with hypertriglyceridemia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Rat liver uncoupling protein 2: changes induced by a fructose-rich diet.

PubMed

Castro, María C; Massa, María L; Del Zotto, Héctor; Gagliardino, Juan J; Francini, Flavio

2011-10-24

To evaluate the role of uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptors (PPARs) in the response of liver to glycoxidative stress triggered by administration of a fructose-rich diet (FRD). We assessed blood glucose in the fasting state and after a glucose load (glucose-oxidase method), serum triglyceride (enzymatic measurement), insulin (radioimmunoassay), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels (colorimetric kits) in control and FRD animals. In liver, we measured UCP2, PPARα, PPARδ and PPARγ gene (real-time PCR) and protein (Western blot) expression, fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) gene expression, as well as triglyceride content. Blood glucose, serum insulin and triglyceride levels, homeostasis model assessment of insulin resistance (HOMA-IR) indexes and impaired glucose tolerance were higher in FRD rats. Whereas UCP2 and PPARδ gene and protein expression increased in these animals; PPARγ levels were lower and those of PPARα remained unchanged. FRD also increased the mRNA expression of PPARδ target genes FAS and GPAT. Our results suggest that a) the increased UCP2 gene and protein expression measured in FRD rats could be part of a compensatory mechanism to reduce reactive oxygen species production induced by the fructose overload, and b) PPARs expression participates actively in the regulation of UCP2 expression, and under the metabolic condition tested, PPARδ played a key role. This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced glycoxidative stress, and to develop appropriate prevention strategies in obesity and type 2 diabetes. Copyright © 2011 Elsevier Inc. All rights reserved.

Postpartum endocrine activities, metabolic attributes and milk yield are influenced by thermal stress in crossbred dairy cows

NASA Astrophysics Data System (ADS)

Ihsanullah; Qureshi, Muhammad Subhan; Suhail, Syed Muhammad; Akhtar, Sohail; Khan, Rifat Ullah

2017-09-01

This study was conducted on 30 freshly parturated multiparous crossbred dairy cows possessing three levels of Holstein Frisian genetic makeup (62.5, 75.0, and 87.5%). Data on temperature humidity index (THI) were classified into comfortable (≤ 71), mild stress (72-79), moderate stress (80-89), and stressful (≥90) zone. Results showed that serum cortisol concentration increased significantly ( P < 0.05) in cows during stressful condition irrespective of genetic makeup compared to the other zones. Daily milk yield (DMY) was significantly ( P < 0.05) lower in cows during stressful condition. Triglyceride was significantly higher in cows with genetic makeup 87.5% compared to the others, while total serum protein was significantly ( P < 0.05) higher in cows during both moderate and stressful conditions. The mean concentration of cortisol and protein increased linearly from comfort to the stressful condition, while mean serum triglyceride, glucose, progesterone (P4), and luteinizing hormone (LH) decreased by moving from comfort to stressful conditions. Results also indicated that higher cortisol level in higher grade crossbred cows was adversely associated with LH concentration and milk yield under thermal stress conditions. Greater triglyceride in high-grade crossbred (87.5%) cows indicates higher fat mobilization reflecting a negative energy balance. We concluded that heat stress increased blood cortisol and protein, and reduced milk yield in dairy cows irresptive of the genetic makeup. In addition, there was no significant difference in blood metabolites and daily milk yield in the different levels of genetic makeup cows.

Postpartum endocrine activities, metabolic attributes and milk yield are influenced by thermal stress in crossbred dairy cows.

PubMed

Ihsanullah; Qureshi, Muhammad Subhan; Suhail, Syed Muhammad; Akhtar, Sohail; Khan, Rifat Ullah

2017-09-01

This study was conducted on 30 freshly parturated multiparous crossbred dairy cows possessing three levels of Holstein Frisian genetic makeup (62.5, 75.0, and 87.5%). Data on temperature humidity index (THI) were classified into comfortable (≤ 71), mild stress (72-79), moderate stress (80-89), and stressful (≥90) zone. Results showed that serum cortisol concentration increased significantly (P < 0.05) in cows during stressful condition irrespective of genetic makeup compared to the other zones. Daily milk yield (DMY) was significantly (P < 0.05) lower in cows during stressful condition. Triglyceride was significantly higher in cows with genetic makeup 87.5% compared to the others, while total serum protein was significantly (P < 0.05) higher in cows during both moderate and stressful conditions. The mean concentration of cortisol and protein increased linearly from comfort to the stressful condition, while mean serum triglyceride, glucose, progesterone (P 4 ), and luteinizing hormone (LH) decreased by moving from comfort to stressful conditions. Results also indicated that higher cortisol level in higher grade crossbred cows was adversely associated with LH concentration and milk yield under thermal stress conditions. Greater triglyceride in high-grade crossbred (87.5%) cows indicates higher fat mobilization reflecting a negative energy balance. We concluded that heat stress increased blood cortisol and protein, and reduced milk yield in dairy cows irresptive of the genetic makeup. In addition, there was no significant difference in blood metabolites and daily milk yield in the different levels of genetic makeup cows.

Relationships among Blood Pressure, Triglycerides and Verbal Learning in African Americans

PubMed Central

Sims, Regina C.; Madhere, Serge; Gordon, Shalanda; Clark, Elijah; Abayomi, Kobi A.; Callender, Clive O.; Campbell, Alfonso L.

2013-01-01

Background Individuals at greater risk for cardiovascular disease (CVD) display poorer cognitive functioning across various cognitive domains. This finding is particularly prevalent among older adults; however, few studies examine these relationships among younger adults or among African Americans. Purpose The objective was to examine the relationships among 2 cardiovascular risk factors, elevated blood pressure and elevated triglycerides, and verbal learning in a community-based sample of African Americans. Methods Measurements of blood pressure and triglycerides were obtained in 121 African-American adults and compared to performance on 3 domains of the California Verbal Learning Test-II (CVLT-II). Results Blood pressure was not related to CVLT-II performance. Triglyceride levels were inversely related to CVLT-II performance. Higher triglyceride levels were associated with poorer immediate, short delay and long delay recall. Conclusions Consistent with studies involving older participants, the current investigation shows that in a nonelderly sample of African Americans, triglyceride levels may be related to cognitive functioning. Because early detection and intervention of vascular-related cognitive impairment may have a salutary effect, future studies should include younger adults to highlight the impact of cardiovascular risk on cognition. PMID:18942281

The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers

PubMed Central

Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

2018-01-01

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO2 inhalation and decapitation. CO2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. PMID:28244216

The effect of balneotherapy on C-reactive protein, serum cholesterol, triglyceride, total antioxidant status and HSP-60 levels.

PubMed

Oláh, Mihály; Koncz, Agnes; Fehér, Judit; Kálmánczhey, Judit; Oláh, Csaba; Balogh, Sándor; Nagy, György; Bender, Tamás

2010-05-01

An increasing body of evidence substantiating the effectiveness of balneotherapy has accumulated during recent decades. In the present study, 42 ambulatory patients (23 males and 19 females, mean age 59.5 years) with degenerative musculoskeletal disease were randomised into one of two groups-bathing in tap water or in mineral water at the same temperature-and subjected to 30-min balneotherapy sessions on 15 occasions. Study parameters comprised serum levels of sensitised C-reactive protein (CRP), plasma lipids, heat shock protein (HSP-60) and total antioxidant status (TAS). In both groups, CRP levels followed a decreasing tendency, which still persisted 3 months later. At 3 months after balneotherapy, serum cholesterol levels were still decreasing in patients who had used medicinal water, but exhibited a trend towards an increase in the control group. Triglyceride levels followed a decreasing trend in both patient groups. TAS showed a declining tendency in both groups. No changes of HSP-60 levels were observed in either group. Balneotherapy with the thermal water from Hajdúszoboszló spa had a more pronounced physiological effect compared to that seen in the control group treated with tap water in a 3 month period.

Estimation and correlation of stress and cholesterol levels in college teachers and housewives of Hyderabad-Pakistan.

PubMed

Wattoo, Feroza Hamid; Memon, Muhammad Saleh; Memon, Allah Nawaz; Wattoo, Muhammad Hamid Sarwar; Tirmizi, Syed Ahmed; Iqbal, Javed

2008-01-01

To evaluate environmental, psychological and physiological stresses in college teachers and housewives, and to correlate with their serum total cholesterol, HDL cholesterol, and LDL cholesterol, and triglyceride levels. This cohort study was performed at the Institute of Biochemistry, University of Sindh, Jamshoro, Pakistan during 2003-2005. Eighty females from middle socioeconomic groups, college teachers (40) and housewives (40) aged between 25-45 years participated in this study and subjects were selected from Hyderabad and its adjoining areas. Environmental, psychological and physiological stress levels were measured with Likert scale. Total cholesterol, LDL cholesterol and HDL cholesterol were measured by CHOD-PAP method and triglyceride levels were measured by GPO method. Housewives had high levels of total cholesterol, LDL cholesterol and triglyceride but low levels of HDL cholesterol were found in college teachers. Environmental, psychological and physiological stresses were significantly higher in housewives as compared to college teachers. Housewives were under more stress than college teachers. High levels of total cholesterol, LDL cholesterol and triglyceride but low levels of HDL cholesterol were found in housewives compared to college teachers.

Estimation of Serum Triglycerides, Serum Cholesterol, Total Protein, IgG Levels in Chronic Periodontitis Affected Elderly Patients: A Cross-Sectional Study

PubMed Central

Saravanan, A. V.; Ravishankar, P. L.; Kumar, Pradeep; Rajapandian, K.; Kalaivani, V.; Rajula, M. Prem Blaisie

2017-01-01

Aim: The present study was conducted to evaluate the serum triglycerides, serum cholesterol, total protein, and IgG levels in elderly patients who were affected by periodontal disease. Materials and Methods: This study was conducted at the Rajah Muthiah Dental College and Hospital in the periodontics division. The study was conducted for a period of 3 months. This study is a prospective analytical study. Sixty individuals who were systemically healthy in the age group of 50 and above were included in this study. Control and experimental groups of 30 participants each were included. Plaque index, gingival index, probing pocket depth, and clinical attachment loss were recorded. Biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were also evaluated and correlated with the periodontal parameters. Data was analyzed using SPSS version 16.0 (IBM Corp., Armonk, NY). The relationship between periodontal status and the biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were evaluated by Student's t-test. Results: There was no significant difference in the plaque and gingival scores between the experimental and control group. It was observed that serum cholesterol level and total protein level was lower in participants suffering from chronic periodontitis. Triglycerides level was significantly elevated in the experimental group. IgG, a level which is not significant, concluded that there is no difference in control and experimental group. Conclusion: It was concluded from the results obtained from the study that there is an association between serum triglycerides, serum cholesterol, total protein, and periodontal disease. However, further longitudinal and well-controlled studies are required to evaluate the relationship between these biochemical parameters and periodontal disease. PMID:28462181

Estimation of Serum Triglycerides, Serum Cholesterol, Total Protein, IgG Levels in Chronic Periodontitis Affected Elderly Patients: A Cross-Sectional Study.

PubMed

Saravanan, A V; Ravishankar, P L; Kumar, Pradeep; Rajapandian, K; Kalaivani, V; Rajula, M Prem Blaisie

2017-01-01

The present study was conducted to evaluate the serum triglycerides, serum cholesterol, total protein, and IgG levels in elderly patients who were affected by periodontal disease. This study was conducted at the Rajah Muthiah Dental College and Hospital in the periodontics division. The study was conducted for a period of 3 months. This study is a prospective analytical study. Sixty individuals who were systemically healthy in the age group of 50 and above were included in this study. Control and experimental groups of 30 participants each were included. Plaque index, gingival index, probing pocket depth, and clinical attachment loss were recorded. Biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were also evaluated and correlated with the periodontal parameters. Data was analyzed using SPSS version 16.0 (IBM Corp., Armonk, NY). The relationship between periodontal status and the biochemical parameters such as serum cholesterol, serum triglycerides, total protein, and IgG levels were evaluated by Student's t-test. There was no significant difference in the plaque and gingival scores between the experimental and control group. It was observed that serum cholesterol level and total protein level was lower in participants suffering from chronic periodontitis. Triglycerides level was significantly elevated in the experimental group. IgG, a level which is not significant, concluded that there is no difference in control and experimental group. It was concluded from the results obtained from the study that there is an association between serum triglycerides, serum cholesterol, total protein, and periodontal disease. However, further longitudinal and well-controlled studies are required to evaluate the relationship between these biochemical parameters and periodontal disease.

Look beyond one's own nose: combination of information from publicly available sources reveals an association of GATA4 polymorphisms with plasma triglycerides.

PubMed

Lamina, Claudia; Coassin, Stefan; Illig, Thomas; Kronenberg, Florian

2011-12-01

GATA4iKO mice exhibit impeded triglyceride absorption from intestine and decreased plasma triglyceride levels. Data in humans are lacking. We hypothesized that triglyceride levels might also be regulated by polymorphisms in the GATA4 gene in humans. We used publicly available data from different sources to evaluate this hypothesis. Our approach is a more often applicable advance to uncover associations and their functional implications which would have been otherwise missed by standard genome-wide association studies (GWAS). We used the publicly available GWAS results from 137 SNPs in the GATA4 region for triglyceride levels. We embedded these results into the comprehensive functional genomics data provided in the UCSC Genome Browser including among others information on regulatory elements and interspecies conservation. A concise graphical presentation is proposed together with an R function for automatic data preparation. This process is presented in an educational manner using a screencast to become most useful for other researchers. We observed several polymorphisms in and around the GATA4 gene which have a significant influence on plasma triglyceride levels with the lowest p-value at SNP rs1466785 (Bonferroni-corrected p-value = 1.76e-5). The bioinformatic evaluation of this locus in publicly available functional genomics data provided converging evidence for the presence of a transcriptional regulator downstream of GATA4. The combination of different sources of data has revealed an association of GATA4 with triglyceride levels in humans. Our evaluation exemplifies how an integrative analysis including both statistical and biological perspectives can shed new light on available association data and reveals novel candidate genes, which are otherwise hidden in the noisy region below genome-wide significance. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

PubMed

Smith, S J; Cases, S; Jensen, D R; Chen, H C; Sande, E; Tow, B; Sanan, D A; Raber, J; Eckel, R H; Farese, R V

2000-05-01

Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

Secular trends in cholesterol lipoproteins and triglycerides and prevalence of dyslipidemias in an urban Indian population

PubMed Central

Gupta, Rajeev; Guptha, Soneil; Agrawal, Aachu; Kaul, Vijay; Gaur, Kiran; Gupta, Vijay P

2008-01-01

Background Coronary heart disease is increasing in urban Indian subjects and lipid abnormalities are important risk factors. To determine secular trends in prevalence of various lipid abnormalities we performed studies in an urban Indian population. Methods Successive epidemiological Jaipur Heart Watch (JHW) studies were performed in Western India in urban locations. The studies evaluated adults ≥ 20 years for multiple coronary risk factors using standardized methodology (JHW-1, 1993–94, n = 2212; JHW-2, 1999–2001, n = 1123; JHW-3, 2002–03, n = 458, and JHW-4 2004–2005, n = 1127). For the present analyses data of subjects 20–59 years (n = 4136, men 2341, women 1795) have been included. In successive studies, fasting measurements for cholesterol lipoproteins (total cholesterol, LDL cholesterol, HDL cholesterol) and triglycerides were performed in 193, 454, 179 and 252 men (n = 1078) and 83, 472, 195, 248 women (n = 998) respectively (total 2076). Age-group specific levels of various cholesterol lipoproteins, triglycerides and their ratios were determined. Prevalence of various dyslipidemias (total cholesterol ≥ 200 mg/dl, LDL cholesterol ≥ 130 mg/dl, non-HDL cholesterol ≥ 160 mg/dl, triglycerides ≥ 150 mg/dl, low HDL cholesterol <40 mg/dl, high cholesterol remnants ≥ 25 mg/dl, and high total:HDL cholesterol ratio ≥ 5.0, and ≥ 4.0 were also determined. Significance of secular trends in prevalence of dyslipidemias was determined using linear-curve estimation regression. Association of changing trends in prevalence of dyslipidemias with trends in educational status, obesity and truncal obesity (high waist:hip ratio) were determined using two-line regression analysis. Results Mean levels of various lipoproteins increased sharply from JHW-1 to JHW-2 and then gradually in JHW-3 and JHW-4. Age-adjusted mean values (mg/dl) in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed a significant increase in total cholesterol (174.9 ± 45, 196.0 ± 42, 187.5 ± 38, 193.5 ± 39, 2-stage least-squares regression R = 0.11, p < 0.001), LDL cholesterol (106.2 ± 40, 127.6 ± 39, 122.6 ± 44, 119.2 ± 31, R = 0.11, p < 0.001), non-HDL cholesterol (131.3 ± 43, 156.4 ± 43, 150.1 ± 41, 150.9 ± 32, R = 0.12, p < 0.001), remnant cholesterol (25.1 ± 11, 28.9 ± 14, 26.0 ± 11, 31.7 ± 14, R = 0.06, p = 0.001), total:HDL cholesterol ratio (4.26 ± 1.3, 5.18 ± 1.7, 5.21 ± 1.7, 4.69 ± 1.2, R = 0.10, p < 0.001) and triglycerides (125.6 ± 53, 144.5 ± 71, 130.1 ± 57, 158.7 ± 72, R = 0.06, p = 0.001) and decrease in HDL cholesterol (43.6 ± 14, 39.7 ± 8, 37.3 ± 6, 42.5 ± 6, R = 0.04, p = 0.027). Trends in age-adjusted prevalence (%) of dyslipidemias in JHW-1, JHW-2, JHW-3 and JHW-4 studies respectively showed insignificant changes in high total cholesterol (26.3, 35.1, 25.6, 26.0, linear curve-estimation coefficient multiple R = 0.034), high LDL cholesterol ≥ 130 mg/dl (24.2, 36.2, 31.0, 22.2, R = 0.062), and high low HDL cholesterol < 40 mg/dl (46.2, 53.3, 55.4, 33.7, R = 0.136). Increase was observed in prevalence of high non-HDL cholesterol (23.0, 33.5, 27.4, 26.6, R = 0.026), high remnant cholesterol (40.1, 40.3, 30.1, 60.6, R = 0.143), high total:HDL cholesterol ratio ≥ 5.0 (22.2, 47.6, 53.2, 26.3, R = 0.031) and ≥ 4.0 (58.6, 72.5, 70.1, 62.0, R = 0.006), and high triglycerides (25.7, 28.2, 17.5, 34.2, R = 0.047). Greater correlation of increasing non-HDL cholesterol, remnant cholesterol, triglycerides and total:HDL cholesterol ratio was observed with increasing truncal obesity than generalized obesity (two-line regression analysis p < 0.05). Greater educational level, as marker of socioeconomic status, correlated significantly with increasing obesity (r2 men 0.98, women 0.99), and truncal obesity (r2 men 0.71, women 0.90). Conclusion In an urban Indian population, trends reveal increase in mean total-, non-HDL-, remnant-, and total:HDL cholesterol, and triglycerides and decline in HDL cholesterol levels. Prevalence of subjects with high total cholesterol did not change significantly while those with high non-HDL cholesterol, cholesterol remnants, triglycerides and total-HDL cholesterol ratio increased. Increasing dyslipidemias correlate significantly with increasing truncal obesity and obesity. PMID:18950504

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.

Maternal loading with very low-density lipoproteins stimulates fetal surfactant synthesis.

PubMed

Ryan, Alan J; Medh, Jheem D; McCoy, Diann M; Salome, Ronald G; Mallampalli, Rama K

2002-08-01

We examined whether administration of very low-density lipoproteins (VLDL) to pregnant rats increases surfactant phosphatidylcholine (PtdCho) content in fetal pre-type II alveolar epithelial cells. VLDL-triglycerides are hydrolyzed to fatty acids by lipoprotein lipase (LPL), an enzyme activated by heparin. Fatty acids released by LPL can incorporate into the PtdCho molecule or activate the key biosynthetic enzyme cytidylyltransferase (CCT). Dams were given BSA, heparin, VLDL, or VLDL with heparin intravenously. Radiolabeled VLDL given to the pregnant rat crossed the placenta and was distributed systemically in the fetus and incorporated into disaturated PtdCho (DSPtdCho) in pre-type II cells. Maternal administration of VLDL with heparin increased DSPtdCho content in cells by 45% compared with control (P < 0.05). VLDL produced a dose-dependent, saturable, and selective increase in CCT activity. VLDL did not significantly alter immunoreactive CCT content but increased palmitic, stearic, and oleic acids in pre-type II cells. Furthermore, hypertriglyceridemic apolipoprotein E knockout mice contained significantly greater levels of DSPtdCho content in alveolar lavage and CCT activity compared with either LDL receptor knockout mice or wild-type controls that have normal serum triglycerides. Thus the nutritional or genetic modulation of serum VLDL-triglycerides provides specific fatty acids that stimulate PtdCho synthesis and CCT activity thereby increasing surfactant content.

Alterations in the lipid metabolism of rat aorta: effects of vitamin a deficiency.

PubMed

Gatica, Laura V; Vega, Verónica A; Zirulnik, Fanny; Oliveros, Liliana B; Gimenez, María S

2006-01-01

Antioxidants are known to reduce cardiovascular disease by reducing the concentration of free radicals in the vessel wall and by preventing the oxidative modification of low-density lipoproteins. The prooxidative effect of a vitamin-A-deficient diet on the aorta has previously been demonstrated by us. In this study, the lipid metabolism in the aorta of rats fed on a vitamin-A-deficient diet was evaluated. Vitamin A deficiency induced a hypolipidemic effect (lower serum triglyceride and cholesterol levels) and a decreased serum paraoxonase 1/arylesterase activity. The concentrations of triglycerides, total cholesterol, free and esterified cholesterol, and phospholipids were increased in the aorta of vitamin-A-deficient rats. The phospholipid compositions showed an increase in phosphatidylcholine (PC), phosphatidylinositol plus phosphatidylserine and phosphatidylethanolamine, a decrease in sphingomyelin, and no change in phosphatidylglycerol. In the aorta, the increase in triglycerides was associated with an increased fatty acid synthesis and mRNA expression of diacylglycerol acyltransferase 1. The increased PC content was attributed to an increased synthesis, as measured by [methyl-(14)C]choline incorporation into PC and high CTP:phosphocholine cytidylyltransferase-alpha mRNA expression. The cholesterol synthesis, evaluated by [1-(14)C]acetate incorporated into cholesterol and mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, did not change. The lipoprotein lipase and lectin-like oxidized low-density lipoprotein receptor 1 mRNA expression levels increased in the aorta of vitamin-A-deficient animals. The incorporation of vitamin A into the diet of vitamin-A-deficient rats reverted all the changes observed. These results indicate that a vitamin-A-deficient diet,in addition to having a prooxidative effect, alters the aorta lipid metabolism.

Serum Amino Acid Profiles in Childhood Predict Triglyceride Level in Adulthood: A 7-Year Longitudinal Study in Girls.

PubMed

Wiklund, Petri; Zhang, Xiaobo; Tan, Xiao; Keinänen-Kiukaanniemi, Sirkka; Alen, Markku; Cheng, Sulin

2016-05-01

Branched-chain and aromatic amino acids are associated with high risk of developing dyslipidemia and type II diabetes in adults. This study aimed to examine whether serum amino acid profiles associate with triglyceride concentrations during pubertal growth and predict hypertriglyceridemia in early adulthood. This was a 7.5-year longitudinal study. The study was conducted at the Health Science Laboratory, University of Jyväskylä. A total of 396 nondiabetic Finnish girls aged 11.2 ± 0.8 years at the baseline participated in the study. Body composition was assessed by dual-energy x-ray absorptiometry; serum concentrations of glucose, insulin, and triglyceride by enzymatic photometric methods; and amino acids by nuclear magnetic resonance spectroscopy. Serum leucine and isoleucine correlated significantly with future triglyceride, independent of baseline triglyceride level (P < .05 for all). In early adulthood (at the age of 18 years), these amino acids were significantly associated with hypertriglyceridemia, whereas fat mass and homeostasis model assessment of insulin resistance were not. Leucine was the strongest determinant discriminating subjects with hypertriglyceridemia from those with normal triglyceride level (area under the curve, 0.822; 95% confidence interval, 0.740-0.903; P = .000001). Serum leucine and isoleucine were associated with future serum triglyceride levels in girls during pubertal growth and predicted hypertriglyceridemia in early adulthood. Therefore, these amino acid indices may serve as biomarkers to identify individuals at high risk for developing hypertriglyceridemia and cardiovascular disease later in life. Further studies are needed to elucidate the role these amino acids play in the lipid metabolism.

Role of leptin in body temperature regulation and lipid metabolism following splenectomy.

PubMed

Rosa, T S; Amorim, C E N; Barros, C C; Haro, A S; Wasinski, F; Russo, F J; Bacurau, R F P; Araujo, R C

2015-12-01

The physiological changes in serum triglycerides and body temperature that are induced by splenectomy are poorly understood. Therefore, the aim of this study was to investigate parameters related to lipid and glucose metabolism, as well as thermoregulation, in splenectomized mice. Splenectomized and sham-operated WT mice (C57Bl/6) and ob/ob mice were randomly divided and treated with a standard or high fat diet, and several metabolic parameters and the body temperature were investigated. Splenectomy induced a significant increase in triglyceride levels regardless of the diet. It was found that the splenectomized WT mice showed greater serum leptin and insulin levels compared with the sham-operated mice. Additionally, the body temperatures of the splenectomized WT mice were greater than the body temperatures of the control animals regardless of diet; this result too was observed without any significant change in the temperature of the splenectomized ob/ob animals. The results suggest that splenectomy interferes with serum triglyceride metabolism and body temperature regardless of the fat content in the diet and that leptin is involved in the regulation of body temperature related to splenectomy.

Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

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

Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.

2013-01-01

Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes wemore » successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.« less

Physiologic and Genetic Evidence Links Hemopexin to Triglycerides in Mice and Humans

PubMed Central

Lawson, Heather A; Zayed, Mohamed; Wayhart, Jessica P; Fabbrini, Elisa; Love-Gregory, Latisha; Klein, Samuel; Semenkovich, Clay F

2017-01-01

Background/Objectives Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. Subjects/Methods Hemopexin was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both reproductive fatpads and livers of mice representing three strains, LG/J (n = 25), SM/J (n = 27) and C57Bl/6J (n = 19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n = 18) and of metabolically normal (n = 24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n = 18). Results Hemopexin expression in mouse adipose tissue, but not liver, was regulated by dietary fat regardless of genetic background. Hemopexin increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of hemopexin based on metabolic disease status (p < 0.05), and circulating hemopexin levels were correlated with serum triglycerides in these subjects (r = 0.33; p = 0.03). Hemopexin was also found in an unbiased proteomic screen of human atherosclerotic plaques, and shown to display differential abundance based on extent of disease and triglyceride content (p < 0.05). Conclusions Our findings suggest that hemopexin is associated with triglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease. PMID:28119529

Physiologic and genetic evidence links hemopexin to triglycerides in mice and humans.

PubMed

Lawson, H A; Zayed, M; Wayhart, J P; Fabbrini, E; Love-Gregory, L; Klein, S; Semenkovich, C F

2017-04-01

Elevated triglycerides predict insulin resistance and vascular disease in obesity, but how the inert triglyceride molecule is related to development of metabolic disease is unknown. To pursue novel potential mediators of triglyceride-associated metabolic disease, we used a forward genetics approach involving inbred mice and translated our findings to human subjects. Hemopexin (HPX) was identified as a differentially expressed gene within a quantitative trait locus associated with serum triglycerides in an F 16 advanced intercross between the LG/J and SM/J strains of mice. Hpx expression was evaluated in both the reproductive fat pads and livers of mice representing three strains, LG/J (n=25), SM/J (n=27) and C57Bl/6J (n=19), on high- and low-fat diets. The effect of altered Hpx expression on adipogenesis was studied in 3T3-L1 cells. Circulating HPX protein along with HPX expression were characterized in subcutaneous white adipose tissue samples obtained from a cohort of metabolically abnormal (n=18) and of metabolically normal (n=24) obese human subjects. We further examined the relationship between HPX and triglycerides in human atherosclerotic plaques (n=18). HPX expression in mouse adipose tissue, but not in liver, was regulated by dietary fat regardless of genetic background. HPX increased in concert with adipogenesis in 3T3-L1 cells, and disruption of its expression impaired adipocyte differentiation. RNAseq data from the adipose tissue of obese humans showed differential expression of HPX based on metabolic disease status (P<0.05), and circulating HPX levels were correlated with serum triglycerides in these subjects (r=0.33; P=0.03). HPX was also found in an unbiased proteomic screen of human atherosclerotic plaques and shown to display differential abundance based on the extent of disease and triglyceride content (P<0.05). Our findings suggest that HPX is associated with triglycerides and provide a framework for understanding mechanisms underlying lipid metabolism and metabolic disease.

Predicting the development of diabetes using the product of triglycerides and glucose: the Chungju Metabolic Disease Cohort (CMC) study.

PubMed

Lee, Seung-Hwan; Kwon, Hyuk-Sang; Park, Yong-Moon; Ha, Hee-Sung; Jeong, Seung Hee; Yang, Hae Kyung; Lee, Jin-Hee; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Yoon, Kun-Ho

2014-01-01

To determine whether the TyG index, a product of the levels of triglycerides and fasting plasma glucose (FPG) might be a valuable marker for predicting future diabetes. A total of 5,354 nondiabetic subjects who had completed their follow-up visit for evaluating diabetes status were selected from a large cohort of middle-aged Koreans in the Chungju Metabolic Disease Cohort study. The risk of diabetes was assessed according to the baseline TyG index, calculated as ln[fasting triglycerides (mg/dL) × FPG (mg/dL)/2]. The median follow-up period was 4.6 years. During the follow-up period, 420 subjects (7.8%) developed diabetes. The baseline values of the TyG index were significantly higher in these subjects compared with nondiabetic subjects (8.9 ± 0.6 vs. 8.6 ± 0.6; P<0.0001) and the incidence of diabetes increased in proportion to TyG index quartiles. After adjusting for age, gender, body mass index, waist circumference, systolic blood pressure, high-density lipoprotein (HDL)-cholesterol level, a family history of diabetes, smoking, alcohol drinking, education level and serum insulin level, the risk of diabetes onset was more than fourfold higher in the highest vs. the lowest quartile of the TyG index (relative risk, 4.095; 95% CI, 2.701-6.207). The predictive power of the TyG index was better than the triglyceride/HDL-cholesterol ratio or the homeostasis model assessment of insulin resistance. The TyG index, a simple measure reflecting insulin resistance, might be useful in identifying individuals at high risk of developing diabetes.

Predicting the Development of Diabetes Using the Product of Triglycerides and Glucose: The Chungju Metabolic Disease Cohort (CMC) Study

PubMed Central

Lee, Seung-Hwan; Kwon, Hyuk-Sang; Park, Yong-Moon; Ha, Hee-Sung; Jeong, Seung Hee; Yang, Hae Kyung; Lee, Jin-Hee; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Yoon, Kun-Ho

2014-01-01

Background To determine whether the TyG index, a product of the levels of triglycerides and fasting plasma glucose (FPG) might be a valuable marker for predicting future diabetes. Methods A total of 5,354 nondiabetic subjects who had completed their follow-up visit for evaluating diabetes status were selected from a large cohort of middle-aged Koreans in the Chungju Metabolic Disease Cohort study. The risk of diabetes was assessed according to the baseline TyG index, calculated as ln[fasting triglycerides (mg/dL) × FPG (mg/dL)/2]. The median follow-up period was 4.6 years. Results During the follow-up period, 420 subjects (7.8%) developed diabetes. The baseline values of the TyG index were significantly higher in these subjects compared with nondiabetic subjects (8.9±0.6 vs. 8.6±0.6; P<0.0001) and the incidence of diabetes increased in proportion to TyG index quartiles. After adjusting for age, gender, body mass index, waist circumference, systolic blood pressure, high-density lipoprotein (HDL)-cholesterol level, a family history of diabetes, smoking, alcohol drinking, education level and serum insulin level, the risk of diabetes onset was more than fourfold higher in the highest vs. the lowest quartile of the TyG index (relative risk, 4.095; 95% CI, 2.701–6.207). The predictive power of the TyG index was better than the triglyceride/HDL-cholesterol ratio or the homeostasis model assessment of insulin resistance. Conclusions The TyG index, a simple measure reflecting insulin resistance, might be useful in identifying individuals at high risk of developing diabetes. PMID:24587359

A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle.

PubMed

Nakayama, Kazuhiro; Bayasgalan, Tumenbayer; Tazoe, Fumiko; Yanagisawa, Yoshiko; Gotoh, Takaya; Yamanaka, Kazuhiro; Ogawa, Ayumi; Munkhtulga, Lkhagvasuren; Chimedregze, Ulziiburen; Kagawa, Yasuo; Ishibashi, Shun; Iwamoto, Sadahiko

2010-06-01

Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e., Japanese and Mongolians. The genotype of rs174547 (T/C), found to be associated with triglyceride and HDL-C concentrations in the GWAS, was determined in 21,004 Japanese and 1,203 Mongolian individuals. Genotype-phenotype association was assessed by using multiple linear regression models, assuming an additive model of inheritance. The copy number of the rs174547 C allele was significantly associated with increased triglyceride levels (P = 1.5 x 10(-6)) and decreased HDL-C levels (P = 0.03) in the Japanese population. On the other hand, in the Mongolian population, the rs174547 C allele copy number was strongly associated with decreased LDL-C levels (P = 2.6 x 10(-6)), but was not associated with triglyceride and HDL-C levels. The linkage disequilibrium pattern and haplotype structures of SNPs around the FADS1/FADS2 locus showed no marked dissimilarity between Japanese and Mongolian individuals. The present data indicate that the FADS1/FADS2 locus can be added to the growing list of loci involved in polygenic dyslipidemia in Asians. Furthermore, the variable effects of FADS1/FADS2 on plasma lipid profiles in Asians may result from differences in the dietary intake of polyunsaturated fatty acids, which serve as substrates for enzymes encoded by FADS1/FADS2.

The role of α1-adrenergic receptors in regulating metabolism: increased glucose tolerance, leptin secretion and lipid oxidation.

PubMed

Shi, Ting; Papay, Robert S; Perez, Dianne M

2017-04-01

The role of α 1 -adrenergic receptors (α 1 -ARs) and their subtypes in metabolism is not well known. Most previous studies were performed before the advent of transgenic mouse models and utilized transformed cell lines and poorly selective antagonists. We have now studied the metabolic regulation of the α 1A - and α 1B -AR subtypes in vivo using knock-out (KO) and transgenic mice that express a constitutively active mutant (CAM) form of the receptor, assessing subtype-selective functions. CAM mice increased glucose tolerance while KO mice display impaired glucose tolerance. CAM mice increased while KO decreased glucose uptake into white fat tissue and skeletal muscle with the CAM α 1A -AR showing selective glucose uptake into the heart. Using indirect calorimetry, both CAM mice demonstrated increased whole body fatty acid oxidation, while KO mice preferentially oxidized carbohydrate. CAM α 1A -AR mice displayed significantly decreased fasting plasma triglycerides and glucose levels while α 1A -AR KO displayed increased levels of triglycerides and glucose. Both CAM mice displayed increased plasma levels of leptin while KO mice decreased leptin levels. Most metabolic effects were more efficacious with the α 1A -AR subtype. Our results suggest that stimulation of α 1 -ARs results in a favorable metabolic profile of increased glucose tolerance, cardiac glucose uptake, leptin secretion and increased whole body lipid metabolism that may contribute to its previously recognized cardioprotective and neuroprotective benefits.

Fasting and nonfasting triglycerides in cardiovascular and other diseases.

PubMed

Piťha, J; Kovář, J; Blahová, T

2015-01-01

Moderately elevated plasma/serum triglycerides (2-10 mmol/l) signalize increased risk for cardiovascular disease or presence of non-alcoholic steatohepatitis. Extremely elevated triglycerides (more than 10 mmol/l) signalize increased risk for pancreatitis and lipemia retinalis. The concentration of triglycerides is regulated by many genetic and nongenetic factors. Extremely elevated triglycerides not provoked by nutritional factors, especially inappropriate alcohol intake are more likely to have a monogenic cause. On the contrary, mildly to moderately elevated triglycerides are often caused by polygenic disorders; these could be also associated with central obesity, insulin resistance, and diabetes mellitus. Concentration of triglycerides is also closely interconnected with presence of atherogenic remnant lipoproteins, impaired reverse cholesterol transport and more atherogenic small LDL particles. In general, there is tight association between triglycerides and many other metabolic factors including intermediate products of lipoprotein metabolism which are frequently atherogenic. Therefore, reliable evaluation of the independent role of triglycerides especially in atherosclerosis and cardiovascular disease is difficult. In individual cases values of HDL cholesterol, non-HDL cholesterol (total minus HDL cholesterol), non-HDL/nonLDL cholesterol (total minus HDL minus LDL cholesterol, especially in nonfasting status), atherogenic index of plasma and/or apolipoprotein B could help in decisions regarding aggressiveness of treatment.

[Mutations of APOC3 gene, metabolism of triglycerides and reduction of ischemic cardiovascular events].

PubMed

Pirillo, Angela; Catapano, Alberico Luigi

2015-05-01

A direct relationship between high plasma triglyceride (TG) levels and increased risk of cardiovascular disease has been shown in several studies. TG are present in the blood associated with different lipoprotein classes, including hepatically-derived very low density lipoproteins (VLDL) and intestinally-derived chylomicrons. Lipoprotein lipase (LPL) is a key enzyme that hydrolyzes TG, releasing free fatty acids that accumulate in peripheral tissues and remnant lipoproteins, that are then cleared by the liver. LPL activity is finely modulated by several cofactors, including apolipoprotein C-III (apoC-III) which acts as a LPL inhibitor. The key role of apoCIII has been established in several studies: animal models lacking APOC3 gene exhibit reduced plasma TG levels, whereas the overexpression of APOC3 gene led to increased TG levels. In humans, several mutations in APOC3 gene have been identified, leading to lower apoC-III levels and associated with reduced plasma TG levels. Recently, these mutations were found to be associated with a reduced risk for cardiovascular ischemia and coronary heart disease, thus confirming the negative role of apoC-III in TG metabolism and suggesting apoC-III as possible therapeutic target for the management of hypertriglyceridemia.

The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk Prospective Population Study

PubMed Central

Arsenault, Benoit J.; Lemieux, Isabelle; Després, Jean-Pierre; Wareham, Nicholas J.; Kastelein, John J.P.; Khaw, Kay-Tee; Boekholdt, S. Matthijs

2010-01-01

Background Screening for increased waist circumference and hypertriglyceridemia (the hypertriglyceridemic-waist phenotype) has been proposed as an inexpensive approach to identify patients with excess intra-abdominal adiposity and associated metabolic abnormalities. We examined the relationship between the hypertriglyceridemic-waist phenotype to the risk of coronary artery disease in apparently healthy individuals. Methods A total of 21 787 participants aged 45–79 years were followed for a mean of 9.8 (standard deviation 1.7) years. Coronary artery disease developed in 2109 of them during follow-up. The hypertriglyceridemic-waist phenotype was defined as a waist circumference of 90 cm or more and a triglyceride level of 2.0 mmol/L or more in men, and a waist circumference of 85 cm or more and a triglyceride level of 1.5 mmol/L or more in women. Results Compared with participants who had a waist circumference and triglyceride level below the threshold, those with the hypertriglyceridemic-waist phenotype had higher blood pressure indices, higher levels of apolipoprotein B and C-reactive protein, lower levels of high-density lipoprotein cholesterol and apolipoprotein A-I, and smaller low-density lipoprotein particles. Among men, those with the hypertriglyceridemic-waist phenotype had an unadjusted hazard ratio for future coronary artery disease of 2.40 (95% confidence interval [CI] 2.02–2.87) compared with men who did not have the phenotype. Women with the phenotype had an unadjusted hazard ratio of 3.84 (95% CI 3.20–4.62) compared with women who did not have the phenotype. Interpretation Among participants from a European cohort representative of a contemporary Western population, the hypertriglyceridemic-waist phenotype was associated with a deteriorated cardiometabolic risk profile and an increased risk for coronary artery disease. PMID:20643837

The metabolic consequences of infusing emulsions containing medium chain triglycerides for parenteral nutrition: a comparative study with conventional lipid.

PubMed Central

Dennison, A. R.; Ball, M.; Crowe, P. J.; White, K.; Hands, L.; Watkins, R. M.; Kettlewell, M.

1986-01-01

In order to test the hypothesis that medium chain triglycerides (MCT's) are a safe and potentially superior energy source during parenteral nutrition 13 patients were entered into a randomised cross over trial. They received either a long chain triglyceride emulsion (LCT) or a 50% medium chain (MCT)/50% LCT mixture as part of their energy supply. Nitrogen balance was significantly better when MCT/LCT was infused and the greater levels of plasma ketones and lower plasma triglyceride levels suggested that MCT was more readily metabolised in these patients. Routine haematology, biochemistry and liver function tests gave no indication of harmful side effects from MCT. PMID:3089123

Effects of Lactobacillus plantarum MA2 isolated from Tibet kefir on lipid metabolism and intestinal microflora of rats fed on high-cholesterol diet.

PubMed

Wang, Yanping; Xu, Nv; Xi, Aodeng; Ahmed, Zaheer; Zhang, Bin; Bai, Xiaojia

2009-08-01

The objective of this study was to evaluate the effects of Lactobacillus plantarum MA2, an isolate from Chinese traditional Tibet kefir, on cholesterol-lowering and microflora of rat in vivo. Rats were fed on cholesterol-enriched experimental diet, supplemented with lyophilized L. plantarum MA2 powder, with a dose of 10(11) cells/day per mice. The results showed that L. plantarum MA2 feeding significantly lowered serum total cholesterol, low-density lipoprotein cholesterol, and triglycerides level, while there was no change in high-density lipoprotein cholesterol. In addition, liver total cholesterol and triglycerides was also decreased. However, fecal cholesterol and triglycerides was increased significantly (P < 0.05) in comparison with the control. Also, L. plantarum MA2 increased the population of lactic acid bacteria and bifidobacteria in the fecal, but it did not change the number of Escherichia coli as compared to control. Moreover, pH, moisture, and organic acids in the fecal were also measured. The present results indicate the probiotic potential of the L. plantarum MA2 strain in hypocholesterolemic effect and also increasing the probiotic count in the intestine.

The type 2 diabetes and insulin-resistance locus near IRS1 is a determinant of HDL cholesterol and triglycerides levels among diabetic subjects.

PubMed

Sharma, Rajani; Prudente, Sabrina; Andreozzi, Francesco; Powers, Christine; Mannino, Gaia; Bacci, Simonetta; Gervino, Ernest V; Hauser, Thomas H; Succurro, Elena; Mercuri, Luana; Goheen, Elizabeth H; Shah, Hetal; Trischitta, Vincenzo; Sesti, Giorgio; Doria, Alessandro

2011-05-01

SNP rs2943641 near the insulin receptor substrate 1 (IRS1) gene has been found to be associated with type 2 diabetes (T2D) and insulin-resistance in genome-wide association studies. We investigated whether this SNP is associated with cardiovascular risk factors and coronary artery disease (CAD) among diabetic individuals. SNP rs2943641 was typed in 2133 White T2D subjects and tested for association with BMI, serum HDL cholesterol and triglycerides, hypertension history, and CAD risk. HDL cholesterol decreased by 1mg/dl (p = 0.004) and serum triglycerides increased by 6 mg/dl (p = 0.016) for each copy of the insulin-resistance allele. Despite these effects, no association was found with increased CAD risk (OR = 1.00, 95% CI 0.88-1.13). The insulin-resistance and T2D locus near the IRS1 gene is a determinant of lower HDL cholesterol among T2D subjects. However, this effect is small and does not translate into a detectable increase in CAD risk in this population. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PNPLA3 is regulated by glucose in human hepatocytes, and its I148M mutant slows down triglyceride hydrolysis.

PubMed

Perttilä, Julia; Huaman-Samanez, Carolina; Caron, Sandrine; Tanhuanpää, Kimmo; Staels, Bart; Yki-Järvinen, Hannele; Olkkonen, Vesa M

2012-05-15

Liver fat is increased in carriers of the minor G allele in rs738409 (I148M amino acid substitution) in patatin-like phospholipase domain-containing 3 (PNPLA3)/adiponutrin. We studied transcriptional regulation of PNPLA3 in immortalized human hepatocytes (IHH) and human hepatoma cells (HuH7) and the impact of PNPLA3 I148M mutant on hepatocyte triglyceride metabolism. Studies in IHH showed that silencing of the carbohydrate response element-binding protein (ChREBP) abolished induction of PNPLA3 mRNA by glucose. Glucose-dependent binding of ChREBP to a newly identified carbohydrate response element in the PNPLA3 promoter was demonstrated by chromatin immunoprecipitation. Adenoviral overexpression of mouse ChREBP in IHH failed to induce PNPLA3 mRNA. [(3)H]acetate or [(3)H]oleate incorporation with 1-h pulse labeling or 18-h [(3)H]oleate labeling in HuH7 cells showed no effect of PNPLA3 I148M on triglyceride (TG) synthesis in the absence of free fatty acid (FFA) loading. Increased [(3)H]oleate accumulation into triglycerides in I148M-expressing cells was observed after 18 h of labeling in the presence of 200 μM FFA-albumin complexes. This was accompanied by increased PNPLA3 protein levels. The rate of hydrolysis of [(3)H]TG during lipid depletion was decreased significantly by PNPLA3 I148M. Our results suggest that PNPLA3 is regulated in human hepatocytes by glucose via ChREBP. PNPLA3 I148M enhances cellular accumulation of [(3)H]TG in the presence of excess FFA, which is known to stabilize PNPLA3 protein. These data do not exclude an effect of PNPLA3 I148M on hepatocyte lipogenesis but show that the mutant increases the stability of triglycerides.

VLDL metabolism in rats is affected by the concentration and source of dietary protein.

PubMed

Madani, Sihem; Prost, Josiane; Narce, Michel; Belleville, Jacques

2003-12-01

The present study was designed to determine if changes in dietary protein level and source are related to changes in VLDL lipid concentrations and VLDL binding by hepatic membranes and isolated hepatocytes. Male Wistar rats were fed cholesterol-free diets containing 10, 20 or 30 g/100 g casein or highly purified soybean protein for 4 wk. Hepatic, plasma and VLDL lipids, VLDL apo B-100 and VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane were determined. Increasing casein or soybean protein level (from 10 to 30 g/100 g) in the diet increased VLDL apo B-100, indicating an increase in the number of VLDL particles. VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane increased when the protein level increased from 10 to 20 g/100 g in the diet and decreased with 30 g/100 g protein, regardless of protein type. The dietary protein source did not affect plasma total cholesterol concentrations at any protein level. Feeding 20 g/100 g soybean protein compared with casein lowered plasma triglyceride concentrations and VLDL number as measured by decreased VLDL-protein, -phospholipid, -triglyceride, -cholesterol and -apo B-100. VLDL uptake by isolated hepatocytes and VLDL binding to hepatic membrane were higher in rats fed soybean protein than those fed casein. The higher VLDL uptake could be responsible for the hypotriglyceridemia in rats fed soybean protein.

Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease.

PubMed

Kirsch, Richard; Sijtsema, Helene P; Tlali, Mpho; Marais, Adrian D; Hall, Pauline de la M

2006-12-01

This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline-deficient (MCD) model of non-alcoholic fatty liver disease (NAFLD). Iron-loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and DL-methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated. Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14-fold increase in hepatic iron concentration at 12 weeks (P < 0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P < 0.02) and decreased hepatic steatosis (P < 0.01), hepatic triglyceride levels (P < 0.01), hepatic-conjugated dienes (CD; P < 0.02) and serum ALT levels (P < 0.002) at 12 weeks. Reduced hepatic steatosis (P < 0.005) and CD (P < 0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content. Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.

Chronic intermittent hypoxia induces atherosclerosis via activation of adipose angiopoietin-like 4.

PubMed

Drager, Luciano F; Yao, Qiaoling; Hernandez, Karen L; Shin, Mi-Kyung; Bevans-Fonti, Shannon; Gay, Jason; Sussan, Thomas E; Jun, Jonathan C; Myers, Allen C; Olivecrona, Gunilla; Schwartz, Alan R; Halberg, Nils; Scherer, Philipp E; Semenza, Gregg L; Powell, David R; Polotsky, Vsevolod Y

2013-07-15

Obstructive sleep apnea is a risk factor for dyslipidemia and atherosclerosis, which have been attributed to chronic intermittent hypoxia (CIH). Intermittent hypoxia inhibits a key enzyme of lipoprotein clearance, lipoprotein lipase, and up-regulates a lipoprotein lipase inhibitor, angiopoietin-like 4 (Angptl4), in adipose tissue. The effects and mechanisms of Angptl4 up-regulation in sleep apnea are unknown. To examine whether CIH induces dyslipidemia and atherosclerosis by increasing adipose Angptl4 via hypoxia-inducible factor-1 (HIF-1). ApoE(-/-) mice were exposed to intermittent hypoxia or air for 4 weeks while being treated with Angptl4-neutralizing antibody or vehicle. In vehicle-treated mice, hypoxia increased adipose Angptl4 levels, inhibited adipose lipoprotein lipase, increased fasting levels of plasma triglycerides and very low density lipoprotein cholesterol, and increased the size of atherosclerotic plaques. The effects of CIH were abolished by the antibody. Hypoxia-induced increases in plasma fasting triglycerides and adipose Angptl4 were not observed in mice with germline heterozygosity for a HIF-1α knockout allele. Transgenic overexpression of HIF-1α in adipose tissue led to dyslipidemia and increased levels of adipose Angptl4. In cultured adipocytes, constitutive expression of HIF-1α increased Angptl4 levels, which was abolished by siRNA. Finally, in obese patients undergoing bariatric surgery, the severity of nocturnal hypoxemia predicted Angptl4 levels in subcutaneous adipose tissue. HIF-1-mediated increase in adipose Angptl4 and the ensuing lipoprotein lipase inactivation may contribute to atherosclerosis in patients with sleep apnea.

Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid invivo screening method for nanotoxicity

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

Lei Ronghui; Department of Public Health, Xi'an Jiaotong University, Xi'an 710061; Wu Chunqi

2008-10-15

Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using {sup 1}H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose ofmore » 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid {beta}-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by nano-copper. The data generated from the current study completely supports the fact that an integrated metabolomic approach is promising for the development of a rapid invivo screening method for nanotoxicity.« less

Partial deficiency of CTRP12 alters hepatic lipid metabolism

PubMed Central

Tan, Stefanie Y.; Little, Hannah C.; Lei, Xia; Li, Shuoyang; Rodriguez, Susana

2016-01-01

Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/−) male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, Ctrp12 (+/−) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. Unlike male mice, Ctrp12 (+/−) female mice fed a control low-fat diet were indistinguishable from WT littermates. When obesity was induced by high-fat feeding, Ctrp12 (+/−) female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in Ctrp12 (+/−) female mice fed a high-fat diet. Thus, in different dietary and metabolic contexts, loss of a single Ctrp12 allele affects glucose and lipid metabolism in a sex-dependent manner, highlighting the importance of genetic and environmental determinants of metabolic phenotypes. PMID:27815536

Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low-Density Lipoprotein Cholesterol Levels.

PubMed

Kitagami, Masayuki; Yasuda, Ryuta; Toma, Naoki; Shiba, Masato; Nampei, Mai; Yamamoto, Yoko; Nakatsuka, Yoshinari; Sakaida, Hiroshi; Suzuki, Hidenori

2017-08-01

Dyslipidemia is a well-known risk factor for carotid stenosis progression, but triglycerides have attracted little attention. The aim of this study was to assess if serum triglycerides affect progression of carotid stenosis in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. This is a retrospective study in a single hospital consisting of 71 Japanese patients with internal carotid artery stenosis greater than or equal to 50% and normal serum LDL-C levels who underwent angiographic examination with or without the resultant carotid artery stenting or endarterectomy from 2007 to 2011, and were subsequently followed up for 4 years. Clinical factors including fasting serum triglyceride values were compared between the progression (≥10% increase in degree of carotid stenosis on ultrasonography) and the nonprogression groups. During 4 years, 15 patients (21.1%) had carotid stenosis progression on either side. Cox regression analysis demonstrated that symptomatic cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR, 6.228; P = .011) were associated with subsequent progression of carotid stenosis. Kaplan-Meier plots demonstrated that the progression-free survival rate was significantly higher in patients without hypertriglyceridemia and intracranial arteriosclerotic stenosis at baseline. Among patients with moderate to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an important risk factor for progression of carotid stenosis irrespective of surgical treatments. It would be worthwhile to test if triglyceride-lowering medications suppress carotid stenosis progression. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Partial deficiency of CTRP12 alters hepatic lipid metabolism.

PubMed

Tan, Stefanie Y; Little, Hannah C; Lei, Xia; Li, Shuoyang; Rodriguez, Susana; Wong, G William

2016-12-01

Secreted hormones play pivotal roles in tissue cross talk to maintain physiologic blood glucose and lipid levels. We previously showed that C1q/TNF-related protein 12 (CTRP12) is a novel secreted protein involved in regulating glucose metabolism whose circulating levels are reduced in obese and insulin-resistant mouse models. Its role in lipid metabolism, however, is unknown. Using a novel heterozygous mouse model, we show that the loss of a single copy of the Ctrp12 gene (also known as Fam132a and adipolin) affects whole body lipid metabolism. In Ctrp12 (+/-) male mice fed a control low-fat diet, hepatic fat oxidation was upregulated while hepatic VLDL-triglyceride secretion was reduced relative to wild-type (WT) littermates. When challenged with a high-fat diet, Ctrp12 (+/-) male mice had impaired lipid clearance in response to acute lipid gavage, reduced hepatic triglyceride secretion, and greater steatosis with higher liver triglyceride and cholesterol levels. Unlike male mice, Ctrp12 (+/-) female mice fed a control low-fat diet were indistinguishable from WT littermates. When obesity was induced by high-fat feeding, Ctrp12 (+/-) female mice developed mild insulin resistance with impaired insulin tolerance. In contrast to male mice, hepatic triglyceride secretion was increased in Ctrp12 (+/-) female mice fed a high-fat diet. Thus, in different dietary and metabolic contexts, loss of a single Ctrp12 allele affects glucose and lipid metabolism in a sex-dependent manner, highlighting the importance of genetic and environmental determinants of metabolic phenotypes. Copyright © 2016 the American Physiological Society.

Ectopic fat depots and left ventricular function in nondiabetic men with nonalcoholic fatty liver disease.

PubMed

Granér, Marit; Nyman, Kristofer; Siren, Reijo; Pentikäinen, Markku O; Lundbom, Jesper; Hakkarainen, Antti; Lauerma, Kirsi; Lundbom, Nina; Nieminen, Markku S; Taskinen, Marja-Riitta

2015-01-01

Nonalcoholic fatty liver disease has emerged as a novel cardiovascular risk factor. The aim of the study was to assess the effect of different ectopic fat depots on left ventricular (LV) function in subjects with nonalcoholic fatty liver disease. Myocardial and hepatic triglyceride contents were measured with 1.5 T magnetic resonance spectroscopy and LV function, visceral adipose tissue (VAT) and subcutaneous adipose tissue, epicardial and pericardial fat by MRI in 75 nondiabetic men. Subjects were stratified by hepatic triglyceride content into low, moderate, and high liver fat groups. Myocardial triglyceride, epicardial and pericardial fat, VAT, and subcutaneous adipose tissue increased stepwise from low to high liver fat group. Parameters of LV diastolic function showed a stepwise decrease over tertiles of liver fat and VAT, and they were inversely correlated with hepatic triglyceride, VAT, and VAT/subcutaneous adipose tissue ratio. In multivariable analyses, hepatic triglyceride and VAT were independent predictors of LV diastolic function, whereas myocardial triglyceride was not associated with measures of diastolic function. Myocardial triglyceride, epicardial and pericardial fat increased with increasing amount of liver fat and VAT. Hepatic steatosis and VAT associated with significant changes in LV structure and function. The association of LV diastolic function with hepatic triglyceride and VAT may be because of toxic systemic effects. The effects of myocardial triglyceride on LV structure and function seem to be more complex than previously thought and merit further study. © 2014 American Heart Association, Inc.

Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism.

PubMed

Wang, Ying; Liu, Zhenzhen; Han, Yi; Xu, Jiping; Huang, Wen; Li, Zhaoshen

2018-01-01

Medium Chain Triglycerides (MCT) is a dietary supplement and usually used along with medications for treating food absorption disorders including diarrhea, steatorrhea and liver disease. It has been shown that MCT plays a role in lowering weight, and decreasing metabolic syndrome, abdominal obesity and inflammation. However, it is still unknown whether MCT enhances exercise endurance. Here, we demonstrated that MCT containing diet improves high temperature induced exercise performance impairment. We found that MCT up-regulates the expression and protein levels of genes involved in mitochondrial biogenesis and metabolism. Further investigation demonstrated that the increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway. Collectively, our findings indicate a beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism.

Dapagliflozin in patients with type II diabetes mellitus, with and without elevated triglyceride and reduced high-density lipoprotein cholesterol levels.

PubMed

Bays, Harold E; Sartipy, Peter; Xu, John; Sjöström, Carl David; Underberg, James A

Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption. The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels. This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM. Patients with elevated triglyceride (≥150 mg/dL [1.69 mmol/L]) and reduced HDL cholesterol levels (<40 mg/dL [1.04 mmol/L] in men; <50 mg/dL [1.29 mmol/L] in women) were included (group A). The reference group (group B) included patients who did not meet the defined lipid criteria. The effects of dapagliflozin on fasting lipid profiles were generally similar in the 2 lipid groups (ie, groups A and B) and, compared with placebo, were associated with minor increases in non-HDL cholesterol, low-density lipoprotein, and HDL cholesterol levels. The effects on triglyceride levels were inconsistent. The incidence of adverse events (AEs)/serious AEs, and AEs of genital infection, urinary tract infection, volume reduction, renal function, and hypoglycemia were similar in the 2 lipid groups. Patients with T2DM treated with dapagliflozin experienced minor changes in lipid levels; the changes were generally similar in the 2 lipid groups. The clinical significance of these changes in lipids is unclear, especially in view of the positive effects of dapagliflozin on other cardiovascular disease risk factors. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

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

[Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy].

PubMed

2016-01-01

LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. Copyright © 2015. Published by Elsevier España.

Plasma lipoproteins and the synthesis and turnover of plasma triglyceride in normal and genetically obese mice

PubMed Central

Salmon, D. Michael W.; Hems, Douglas A.

1973-01-01

1. Lipoproteins in the plasma of mice were characterized by agarose-gel chromatography and polyacrylamide-gel electrophoresis: genetically obese (ob/ob) mice exhibited hyperlipoproteinaemia (compared with lean mice), largely owing to an increase in the concentration of cholesterol in high-density lipoprotein. Plasma concentrations of triglyceride and phospholipid were not markedly increased in genetically obese mice. 2. The formation of glycerolipids in liver and plasma was investigated with 14C-labelled precursors. The synthesis of hepatic triglyceride and phospholipid from glucose or palmitate was enhanced in ob/ob mice, compared with lean mice. The rate of entry of triglyceride into plasma, calculated from the time-course of incorporation of 14C from [14C]palmitate into plasma triglyceride, was increased in ob/ob mice (0.5μmol of fatty acid/min, compared with 0.2 in lean mice). 3. The removal from plasma of murine lipoprotein triglyceride-[14C]fatty acid was increased in ob/ob mice (half-time 2.2min, compared with 7.2min in lean mice). Similar results were obtained with an injected lipid emulsion (Intralipid). 4. From these measurements, estimates of the rates of turnover of plasma triglyceride in mice (fed on a mixed diet, female, 3 months old) are about 1.0μmol of fatty acid/min in ob/ob mice, and 0.25 in lean mice. 5. The major precursor of hepatic and plasma triglyceride in lean and ob/ob mice was calculated to be plasma free fatty acid. 6. These results are discussed, in connexion with the role of the liver in triglyceride metabolism in mice, especially in relation to genetic obesity. PMID:4360712

Predictive value of early changes in triglycerides and weight for longer-term changes in metabolic measures during olanzapine, ziprasidone or aripiprazole treatment for schizophrenia and schizoaffective disorder post hoc analyses of 3 randomized, controlled clinical trials.

PubMed

Hoffmann, Vicki P; Case, Michael; Stauffer, Virginia L; Jacobson, Jennie G; Conley, Robert R

2010-12-01

The objective of this study was to determine if early changes in triglycerides and weight may be useful in predicting longer-term changes in weight and other metabolic parameters. Data were from three 24- to 28-week randomized, controlled studies comparing olanzapine to ziprasidone or aripiprazole for treatment of schizophrenia. Analyses were restricted to completers with fasting laboratory data at all protocol specified time points. Analyses were primarily descriptive and included mean changes and categorical outcomes. In all treatment groups, participants who did not experience a 20 mg/dL or greater increase in triglycerides at early time points were unlikely to experience a change of 50 mg/dL or more in triglycerides after 6 months. Negative predictive values were 83% to 95%. However, early change in triglycerides was not useful for predicting later change in glucose, cholesterol, or weight. Similarly, early weight change gave robust negative predictive values for longer-term weight change (≥10 kg), but not for change in glucose or cholesterol. Lack of early elevation in triglyceride concentrations was predictive of later lack of substantial increase in triglycerides in olanzapine-, ziprasidone-, and aripiprazole-treated participants. Lack of early elevation in weight was predictive of later lack of substantial increase in weight in all 3 treatment groups. Early monitoring of triglyceride concentrations and weight may help clinicians assess risk that individuals will experience significant increase in triglycerides or weight gain, allowing assessments of potential risks and benefits earlier in treatment. Clinical monitoring is advised throughout treatment for all patients.

Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water.

PubMed

Song, Xuanbo; Li, Ying; Liu, Junqiu; Ji, Xiaohong; Zhao, Lijun; Wei, Yudan

2017-09-01

Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO 2 ) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

Body mass index, triglycerides, glucose, and blood pressure as predictors of type 2 diabetes in a middle-aged Norwegian cohort of men and women.

PubMed

Hjellvik, Vidar; Sakshaug, Solveig; Strøm, Hanne

2012-01-01

Obesity, hypertension, and hypertriglyceridemia are important risk factors for type 2 diabetes (T2D). We wanted to assess the risk associated with these three factors alone and in combination, and the relative importance of these and several other risk factors (eg, nonfasting glucose) as predictors of T2D. Risk factors in a Norwegian population (n = 109,796) aged 40-45 years were measured in health studies in 1995-1999. Blood glucose-lowering drugs dispensed in 2004-2009 were used to estimate the incidence of T2D. Groups based on combinations of body mass index (BMI), diastolic blood pressure, and triglycerides were defined by using the 50% and 90% quantiles for each variable for men and women. The relative importance of BMI, triglycerides, total cholesterol, high-density lipoprotein cholesterol, glucose, blood pressure, and year of birth for predicting T2D was assessed using deviance from univariate and multivariate logistic regression models. Height, weight, and blood pressure were measured. All biomarkers were measured in nonfasting blood samples. In the various groups of BMI, triglycerides, and diastolic blood pressure, the incidence of T2D ranged from 0.5% to 19.7% in men and from 0.15% to 21.8% in women. BMI was the strongest predictor of incident T2D, followed by triglyceride levels in women and glucose levels in men. The inclusion of risk factors other than BMI, glucose, triglycerides, and blood pressure in multivariate models only marginally improved the prediction. BMI was the strongest predictor of type 2 diabetes. At defined levels of BMI, the incidence of T2D varied substantially with triglyceride levels and blood pressure. Thus, controlling triglycerides and blood pressure in middle-aged individuals should be targeted to prevent later onset of T2D.

Hepatocellular integrity in patients requiring parenteral nutrition: comparison of structured MCT/LCT vs. a standard MCT/LCT emulsion and a LCT emulsion.

PubMed

Piper, S N; Röhm, K D; Boldt, J; Odermatt, B; Maleck, W H; Suttner, S W

2008-07-01

The aetiology of parenteral nutrition-associated hepatic injury remains unresolved. The aim of the study was to evaluate the effects of structured triglycerides in parenteral nutrition compared either to a physical medium-chain triglycerides (MCT)/long-chain triglcerides (LCT) mixture or to a LCT emulsion on hepatic integrity. In a randomized, double-blinded trial, we studied 45 patients undergoing abdominal surgery, who were expected to receive parenteral nutrition for 5 days. Patients were allocated to one of three nutrition regimens: Group A (n = 15) received structured triglycerides, Group B (n = 15) a MCT/LCT and Group C (n = 15) a LCT lipid emulsion. Before the start of parenteral nutrition (T0), 24 h (T1), 48 h (T2), 72 h (T3) and 120 h (T4) after start of infusion the following parameters were measured: Alpha-glutathione S-transferase (alpha-GST), alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose and serum triglycerides. At T3 and T4, alpha-GST levels were significantly higher in Group B (T3: 9.4 +/- 9.9; T4: 14.6 +/- 19.5 microg L-1) and Group C (T3: 14.2 +/- 20.8; T4: 22.4 +/- 39.3 microg L-1) compared with the patients receiving structured triglycerides (T3: 1.9 +/- 1.8; T4: 3.2 +/- 2.7 microg L-1). Whereas the mean alpha-GST-levels in structured triglycerides group always remained in the normal range, this was not the case in both other groups at T3 and T4. There were no significant differences concerning ALT, AST and glucose levels. At T3 and T4, triglyceride levels were significantly lower in Group A than in Groups B and C. Hepatic integrity was well retained with the administration of structured triglycerides, whereas both MCT/LCT emulsion and LCT emulsion caused subclinical hepatic injury.

High fat diet feeding results in gender specific steatohepatitis and inflammasome activation.

PubMed

Ganz, Michal; Csak, Timea; Szabo, Gyongyi

2014-07-14

To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge. In this study, we used a high fat diet (HFD) feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States. We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively, and evaluated the extent of liver damage, steatosis, and inflammasome activation. Our methods included histopathological analysis to assess liver damage and steatosis, which involved H and E and oil-red-o staining; biochemical studies to look at ALT and triglyceride levels; RNA analysis using quantitative polymerase chain reaction; and cytokine analysis, which included the enzyme-linked immunosorbent assay method to look at interleukin (IL)-1β and tumor necrosis factor-α (TNFα) levels. Furthermore, at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests (ITT) and glucose tolerance tests. There was no insulin resistance, steatosis, or inflammasome activation at 6 wk. In contrast, at 16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male, but not female mice. In males, elevated alanine aminotransferase and triglyceride levels, indicated liver damage and steatosis, respectively. Increased liver TNFα and monocyte chemoattractant protein-1 mRNA and protein, correlated with steatohepatitis. The inflammasome components, adaptor molecule, Aim2, and NOD-like receptor 4, increased at the mRNA level, and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1β protein levels in male mice fed a long-term HFD. Male mice on HFD had increased α-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis. In contrast, female mice displayed only elevated triglyceride levels, steatosis, and no fibrosis. Our data indicate gender differences in NASH. Male mice fed a long-term HFD display steatohepatitis and inflammasome activation, whereas female mice have steatosis without inflammation.

A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese

PubMed Central

Jiang, Chao Qiang; Liu, Bin; Cheung, Bernard MY; Lam, Tai Hing; Lin, Jie Ming; Li Jin, Ya; Yue, Xiao Jun; Ong, Kwok Leung; Tam, Sidney; Wong, Ka Sing; Tomlinson, Brian; Lam, Karen SL; Thomas, G Neil

2010-01-01

Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 (APOA5) gene have been associated with hypertriglyceridaemia. We investigated which SNPs in the APOA5 gene were associated with triglyceride levels in two independent Chinese populations. In all, 1375 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study were genotyped for five tagging SNPs chosen from HapMap. Replication was sought in 1996 subjects from the Guangzhou Biobank Cohort Study. Among the five SNPs, rs662799 (-1131T>C) was strongly related to log-transformed triglyceride levels among Hong Kong subjects (β=0.192, P=2.6 × 10−13). Plasma triglyceride level was 36.1% higher in CC compared to TT genotype. This association was confirmed in Guangzhou subjects (β=0.159, P=1.3 × 10−12), and was significantly irrespective of sex, age group, obesity, metabolic syndrome, hypertension, diabetes, smoking and alcohol drinking. The odds ratios and 95% confidence interval for plasma triglycerides ≥1.7 mmol/l associated with TC and CC genotypes were, respectively, 1.81 (1.37–2.39) and 2.22 (1.44–3.43) in Hong Kong and 1.27 (1.05–1.54) and 1.97 (1.42–2.73) in Guangzhou. Haplotype analysis suggested the association was due to rs662799 only. The corroborative findings in two independent populations indicate that the APOA5-1131T>C polymorphism is an important and clinically relevant determinant of plasma triglyceride levels in the Chinese population. PMID:20571505

Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias

PubMed Central

Malaguarnera, M; Giugno, I; Ruello, P; Rizzo, M; Motta, M; Mazzoleni, G

1999-01-01

Aims In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia. Methods Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1 ±10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values ≤4.5 mmol l−1; group B triglyceride values > 4.5 mmol l− 1). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks. Results Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only. Conclusions Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non-diabetic patients affected by severe hypertriglyceridaemia. PMID:10583032

TRB3 gene silencing activates AMPK in adipose tissue with beneficial metabolic effects in obese and diabetic rats.

PubMed

Sun, Xiaoyan; Song, Ming; Wang, Hui; Zhou, Huimin; Wang, Feng; Li, Ya; Zhang, Yun; Zhang, Wei; Zhong, Ming; Ti, Yun

2017-06-17

Our previous study had suggested Tribbles homolog 3 (TRB3) might be involved in metabolic syndrome via adipose tissue. Given prior studies, we sought to determine whether TRB3 plays a major role in adipocytes and adipose tissue with beneficial metabolic effects in obese and diabetic rats. Fully differentiated 3T3-L1 adipocytes were incubated to induce insulin resistant adipocytes. Forty male Sprague-Dawley rats were all fed high-fat (HF) diet. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin (STZ). Compared with control group, in insulin resistant adipocytes, protein levels of insulin receptor substrate-1(IRS-1), glucose transporter 4(GLUT4) and phosphorylated-AMP-activated protein kinase (p-AMPK)were reduced, TRB3 protein level and triglyceride level were significantly increased, glucose uptake was markedly decreased. TRB3 silencing alleviated adipocytes insulin resistance. With TRB3 gene silencing, protein levels of IRS-1, GLUT4 and p-AMPK were significantly increased in adipocytes. TRB3 gene silencing decreased blood glucose, ameliorated insulin sensitivity and adipose tissue remodeling in diabetic rats. TRB3 silencing decreased triglyceride, increased glycogen simultaneously in diabetic epididymal and brown adipose tissues (BAT). Consistently, p-AMPK levels were increased in diabetic epididymal adipose tissue, and BAT after TRB3-siRNA treatment. TRB3silencing increased phosphorylation of Akt in liver, and improved liver insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Lipid, lipoproteins, C-reactive protein, and hemostatic factors at baseline in the diabetes prevention program.

PubMed

2005-10-01

Individuals with impaired glucose tolerance (IGT) appear to be at increased risk for cardiovascular disease (CVD) due at least in part to an increased prevalence of risk factors. We evaluated lipid, lipoprotein, C-reactive protein (CRP), fibrinogen, and tissue plasminogen activator (tPA) levels at study entry in the largest multiethnic cohort of participants with IGT described, namely in the Diabetes Prevention Program (DPP). Measurements were performed at the baseline visit of 3,819 randomized participants of the DPP. Among 3,622 participants who were not taking lipid-lowering medicines, cardiovascular risk factors were analyzed in relation to demographic, anthropometric, and metabolic measures. Major determinants of risk factors were assessed in multivariate analysis. Over 40% of participants had elevated triglyceride, LDL cholesterol, and CRP levels and reduced HDL cholesterol levels. Men had higher triglyceride and tPA and lower HDL cholesterol concentrations and smaller LDL particle size than women, whereas women had higher CRP and fibrinogen levels. African Americans had less dyslipidemia but higher fibrinogen levels, and Asian Americans had lower CRP and fibrinogen levels than Caucasians and Hispanics. The surrogate measure of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) had the strongest association with HDL cholesterol, triglyceride, and tPA levels and LDL particle size. BMI had the greatest influence on CRP and fibrinogen levels. Using median splits of indexes of insulin resistance and insulin secretion (insulin-to-glucose ratio), participants with greater insulin resistance had a more adverse CVD risk-factor profile, whereas insulin secretion had little influence on risk factors. The pattern of CVD risk factors in participants with IGT in the DPP exhibits substantial heterogeneity and is significantly influenced by race, sex, and age, as well as by obesity, glucose, and insulin measures. The degree of insulin resistance, as reflected by HOMA-IR, showed the greatest association with the cardiovascular risk factors.

Lipid, Lipoproteins, C-Reactive Protein, and Hemostatic Factors at Baseline in the Diabetes Prevention Program

PubMed Central

2005-01-01

OBJECTIVE — Individuals with impaired glucose tolerance (IGT) appear to be at increased risk for cardiovascular disease (CVD) due at least in part to an increased prevalence of risk factors. We evaluated lipid, lipoprotein, C-reactive protein (CRP), fibrinogen, and tissue plasminogen activator (tPA) levels at study entry in the largest multiethnic cohort of participants with IGT described, namely in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS — Measurements were performed at the baseline visit of 3,819 randomized participants of the DPP. Among 3,622 participants who were not taking lipid-lowering medicines, cardiovascular risk factors were analyzed in relation to demographic, anthropometric, and metabolic measures. Major determinants of risk factors were assessed in multivariate analysis. RESULTS — Over 40% of participants had elevated triglyceride, LDL cholesterol, and CRP levels and reduced HDL cholesterol levels. Men had higher triglyceride and tPA and lower HDL cholesterol concentrations and smaller LDL particle size than women, whereas women had higher CRP and fibrinogen levels. African Americans had less dyslipidemia but higher fibrinogen levels, and Asian Americans had lower CRP and fibrinogen levels than Caucasians and Hispanics. The surrogate measure of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]) had the strongest association with HDL cholesterol, triglyceride, and tPA levels and LDL particle size. BMI had the greatest influence on CRP and fibrinogen levels. Using median splits of indexes of insulin resistance and insulin secretion (insulin-to-glucose ratio), participants with greater insulin resistance had a more adverse CVD risk-factor profile, whereas insulin secretion had little influence on risk factors. CONCLUSIONS — The pattern of CVD risk factors in participants with IGT in the DPP exhibits substantial heterogeneity and is significantly influenced by race, sex, and age, as well as by obesity, glucose, and insulin measures. The degree of insulin resistance, as reflected by HOMA-IR, showed the greatest association with the cardiovascular risk factors. PMID:16186282

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance.

PubMed

Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang

2017-10-03

The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR.

The evolving relationship between adiponectin and insulin sensitivity in hepatitis C patients during viral clearance

PubMed Central

Chang, Ming-Ling; Kuo, Chia-Jung; Pao, Li-Heng; Hsu, Chen-Ming; Chiu, Cheng-Tang

2017-01-01

ABSTRACT Background: The evolution of the relationship between adiponectin and insulin sensitivity in hepatitis C virus (HCV) patients during viral clearance is unclear and warrants investigation. Methods: A prospective study including 747 consecutive chronic hepatitis C (CHC) patients, of whom 546 had completed a course of anti-HCV therapy and underwent pre-, peri- and post-therapy surveys for anthropomorphic, viral, metabolic and hepatic profiles and adiponectin levels, was conducted in a tertiary care center. Results: Multivariate analyses indicated associations of sex, triglyceride levels and hepatic steatosis with adiponectin levels and of triglyceride levels and interferon λ3 (IFNL3) genotype with homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels before anti-HCV therapy. In patients with a sustained virological response (SVR; n = 455), at 24 weeks post-therapy, sex, BMI, aspartate aminotransferase to platelet ratio index (APRI), HOMA-IR and steatosis were associated with adiponectin levels, and IFNL3 genotype was associated with HOMA-IR levels. GEE analysis demonstrated that SVR affected longitudinal trends in adiponectin levels. Compared with pre-therapy levels, adiponectin and APRI levels decreased 24 weeks post-therapy in SVR patients, regardless of baseline insulin resistance (IR). However, HOMA-IR levels decreased in SVR patients with baseline IR but increased in those without baseline IR. Compared with controls, immunohistochemical studies showed that pre-therapy CHC patients had higher hepatic adiponectin expression associated with hepatic fibrosis. Conclusions: During HCV infection, adiponectin may affect insulin sensitivity through triglycerides. After viral clearance, adiponectin levels were directly associated with insulin sensitivity and decreased upon improved hepatic fibrosis; with a link to the IFNL3 genotype, insulin sensitivity improved only in patients with baseline IR. PMID:28267407

Effects of acute temperature change, confinement and housing on plasma corticosterone in water snakes, Nerodia sipedon (Colubridae: Natricinae).

PubMed

Sykes, Kyle Lea; Klukowski, Matthew

2009-03-01

Body temperature affects many aspects of reptilian behavior and physiology, but its effect on hormonal secretion has been little studied, especially in snakes. Major objectives of this study were to determine if acute changes in body temperature during confinement influenced plasma corticosterone levels and if initial body temperatures upon capture in the field were related to baseline corticosterone levels in water snakes (Nerodia sipedon). Water snakes were bled upon capture in the field and after one hour of confinement in a cooled, control, or heated incubator. Since little is known about the potential metabolic changes in response to stress in reptiles, plasma triglyceride levels were also measured. Upon completion of the field study, snakes were housed for 5-8 days without food to determine the effect of chronic stress on both corticosterone and triglyceride levels. Plasma corticosterone concentrations were measured using enzyme-linked immunosorbant assay (ELISA) and plasma triglycerides were determined enzymatically. In the field, experimental alterations of body temperature during confinement had no effect on corticosterone levels. Similarly, there was no correlation between initial body temperature and baseline plasma corticosterone concentrations. However, post-confinement corticosterone levels were approximately three-times greater in females than males. Plasma triglyceride levels were not affected by temperature treatment, confinement, or sex. Compared to field values, both baseline and post-confinement corticosterone levels were elevated after the chronic stress of short-term laboratory housing but triglyceride levels decreased. Overall, these results indicate that sex but not body temperature has a major influence on the adrenocortical stress response in Nerodia sipedon.

In vivo biochemical and gene expression analyses of the antioxidant activities and hypocholesterolaemic properties of Tamarindus indica fruit pulp extract.

PubMed

Lim, Chor Yin; Mat Junit, Sarni; Abdulla, Mahmood Ameen; Abdul Aziz, Azlina

2013-01-01

Tamarindus indica (T. indica) is a medicinal plant with many biological activities including anti-diabetic, hypolipidaemic and anti-bacterial activities. A recent study demonstrated the hypolipidaemic effect of T. indica fruit pulp in hamsters. However, the biochemical and molecular mechanisms responsible for these effects have not been fully elucidated. Hence, the aims of this study were to evaluate the antioxidant activities and potential hypocholesterolaemic properties of T. indica, using in vitro and in vivo approaches. The in vitro study demonstrated that T. indica fruit pulp had significant amount of phenolic (244.9 ± 10.1 mg GAE/extract) and flavonoid (93.9 ± 2.6 mg RE/g extract) content and possessed antioxidant activities. In the in vivo study, hamsters fed with high-cholesterol diet for ten weeks showed elevated serum triglyceride, total cholesterol, HDL-C and LDL-C levels. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters significantly lowered serum triglyceride, total cholesterol and LDL-C levels but had no effect on the HDL-C level. The lipid-lowering effect was accompanied with significant increase in the expression of Apo A1, Abcg5 and LDL receptor genes and significant decrease in the expression of HMG-CoA reductase and Mtp genes. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters also protected against oxidative damage by increasing hepatic antioxidant enzymes, antioxidant activities and preventing hepatic lipid peroxidation. It is postulated that tamarind fruit pulp exerts its hypocholesterolaemic effect by increasing cholesterol efflux, enhancing LDL-C uptake and clearance, suppressing triglyceride accumulation and inhibiting cholesterol biosynthesis. T. indica fruit pulp has potential antioxidative effects and is potentially protective against diet-induced hypercholesterolaemia.

In Vivo Biochemical and Gene Expression Analyses of the Antioxidant Activities and Hypocholesterolaemic Properties of Tamarindus indica Fruit Pulp Extract

PubMed Central

Lim, Chor Yin; Mat Junit, Sarni; Abdulla, Mahmood Ameen; Abdul Aziz, Azlina

2013-01-01

Background Tamarindus indica (T. indica) is a medicinal plant with many biological activities including anti-diabetic, hypolipidaemic and anti-bacterial activities. A recent study demonstrated the hypolipidaemic effect of T. indica fruit pulp in hamsters. However, the biochemical and molecular mechanisms responsible for these effects have not been fully elucidated. Hence, the aims of this study were to evaluate the antioxidant activities and potential hypocholesterolaemic properties of T. indica, using in vitro and in vivo approaches. Methodology/Principal Findings The in vitro study demonstrated that T. indica fruit pulp had significant amount of phenolic (244.9±10.1 mg GAE/extract) and flavonoid (93.9±2.6 mg RE/g extract) content and possessed antioxidant activities. In the in vivo study, hamsters fed with high-cholesterol diet for ten weeks showed elevated serum triglyceride, total cholesterol, HDL-C and LDL-C levels. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters significantly lowered serum triglyceride, total cholesterol and LDL-C levels but had no effect on the HDL-C level. The lipid-lowering effect was accompanied with significant increase in the expression of Apo A1, Abcg5 and LDL receptor genes and significant decrease in the expression of HMG-CoA reductase and Mtp genes. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters also protected against oxidative damage by increasing hepatic antioxidant enzymes, antioxidant activities and preventing hepatic lipid peroxidation. Conclusion/Significance It is postulated that tamarind fruit pulp exerts its hypocholesterolaemic effect by increasing cholesterol efflux, enhancing LDL-C uptake and clearance, suppressing triglyceride accumulation and inhibiting cholesterol biosynthesis. T. indica fruit pulp has potential antioxidative effects and is potentially protective against diet-induced hypercholesterolaemia. PMID:23894592

Purified fish oil eliminating linoleic and alpha linolenic acid meets essential fatty acid requirements in rats.

PubMed

Ling, Pei-Ra; Puder, Mark; Bistrian, Bruce R

2012-10-01

This study examined whether purified fish oil (PFO) supplemented to an essential fatty acid deficient (EFAD) diet meets EFA needs in rats. The EFAD diet contained 10% hydrogenated coconut oil (HCO). A similar diet contained 7% HCO and 3% PFO which also provided 2.84% arachidonic acid (AA), 52.50% eicosapentaenoic acid (EPA) and 35.73% docosahexaenoic acid (DHA) but no linoleic acid (LA) or alpha linolenic acid (ALA). A 10% soybean oil control diet provided ample LA and ALA. After 4 weeks of feeding, blood glucose, plasma triglyceride and phospholipid fatty acid profiles, C-reactive protein (CRP), TNF and IL-6 were determined after saline or LPS injection. EFAD developed with the HCO diet with triene:tetraene ratios in plasma phospholipids >.20, which remained <.02 with the control and HCO+PFO diets. Mead acid levels significantly increased by a factor of 10 with the HCO diet compared to the AIN and HCO+PFO diets and were significantly lowest with the HCO+PFO diet. 18:1 n9 levels were significantly higher in plasma phospholipids and triglycerides with the HCO diet. CRP levels were significantly highest with the control diet and significantly lowest with the HCO diet. LPS significantly increased 18:1 n9 and cytokines, and decreased AA and plasma glucose in all diets and significantly increased plasma triglycerides and decreased plasma glucose in controls. Providing AA, EPA and DHA in EFAD prevents EFAD over the short-term as reflected in Mead acid production, triene:tetraene ratio, and de novo lipogenesis and may reduce the inflammatory response to LPS. Copyright © 2012 Elsevier Inc. All rights reserved.

[Severely increased serum lipid levels in diabetic ketoacidosis - case report].

PubMed

Stefansson, Hrafnkell; Sigvaldason, Kristinn; Kjartansson, Hilmar; Sigurjonsdottir, Helga Águsta

2017-01-01

Severe hypertriglyceridemia is a known, but uncommon complication of diabetic ketoacidosis. We discuss the case of a 23-year-old, previously healthy, woman who initially presented to the emergency department with abdominal pain. Grossly lipemic serum due to extremely high triglyceride (38.6 mmol/L) and cholesterol (23.2 mmol/L) levels were observed with a high blood glucose (23 mmol/L) and a low pH of 7.06 on a venous blood gas. She was treated successfully with fluids and insulin and had no sequale of pancreatitis or cerebral edema. Her triglycerides and cholesterol was normalized in three days and she was discharged home on insulin therapy after five days. Further history revealed a recent change in diet with no meat, fish or poultry consumption in the last 12 months and concomitantly an increase in carbohydrate intake which might have contributed to her extremely high serum lipid levels. This case demonstrates that clinicians should be mindful of the different presentations of diabetic ketoacidosis. Key words: diabetic ketoacidosis, hypertriglyceridemia, hyperlipidemia, vegan diet, carbohydrate diet. Correspondence: Hrafnkell Stefansson, hrafnkell.stefans@gmail.com.

Association of canine obesity with reduced serum levels of C-reactive protein.

PubMed

Veiga, Angela P M; Price, Christopher A; de Oliveira, Simone T; Dos Santos, Andréa P; Campos, Rómulo; Barbosa, Patricia R; González, Félix H D

2008-03-01

The prevalence of obesity is increasing in dogs as well as in humans. C-reactive protein (CRP) is an important tool for the detection of inflammation and/or early tissue damage and is linked to obesity in humans. The objective of the present study was to determine if serum CRP levels are altered in obese dogs. Fifteen lean (control group) and 16 overweight (obese group) dogs were examined. Blood samples were collected under fasted conditions for serum determination of CRP, glucose, insulin, cholesterol, triglyceride, and fructosamine. Results indicated that obese dogs were insulin resistant because serum insulin and insulin/glucose ratios were higher than in lean dogs (P < or = 0.05). Serum CRP concentrations were lower in obese dogs than in controls (P < or = 0.001). C-reactive protein was negatively correlated with insulin/glucose ratio (R = -0.42) and cholesterol (R = -0.39; P < or = 0.05). Furthermore, levels of cholesterol, triglycerides, and fructosamine were increased in the obese group compared with the control group. Based on these results, it can be postulated that CRP production is inhibited by obesity and insulin resistance in dogs.

Optimizing human hepatocyte models for metabolic phenotype and function: effects of treatment with dimethyl sulfoxide (DMSO).

PubMed

Nikolaou, Nikolaos; Green, Charlotte J; Gunn, Pippa J; Hodson, Leanne; Tomlinson, Jeremy W

2016-11-01

Primary human hepatocytes are considered to be the "gold standard" cellular model for studying hepatic fatty acid and glucose metabolism; however, they come with limitations. Although the HepG2 cell line retains many of the primary hepatocyte metabolic functions they have a malignant origin and low rates of triglyceride secretion. The aim of this study was to investigate whether dimethyl sulfoxide supplementation in the media of HepG2 cells would enhance metabolic functionality leading to the development of an improved in vitro cell model that closely recapitulates primary human hepatocyte metabolism. HepG2 cells were cultured in media containing 1% dimethyl sulfoxide for 2, 4, 7, 14, and 21 days. Gene expression, protein levels, intracellular triglyceride, and media concentrations of triglyceride, urea, and 3-hydroxybutyrate concentrations were measured. Dimethyl sulfoxide treatment altered the expression of genes involved in lipid (FAS, ACC1, ACC2, DGAT1, DGAT2, SCD) and glucose (PEPCK, G6Pase) metabolism as well as liver functionality (albumin, alpha-1-antitrypsin, AFP). mRNA changes were paralleled by alterations at the protein level. DMSO treatment decreased intracellular triglyceride content and lactate production and increased triglyceride and 3-hydroxybutyrate concentrations in the media in a time-dependent manner. We have demonstrated that the addition of 1% dimethyl sulfoxide to culture media changes the metabolic phenotype of HepG2 cells toward a more primary human hepatocyte phenotype. This will enhance the currently available in vitro model systems for the study of hepatocyte biology related to pathological processes that contribute to disease and their response to specific therapeutic interventions. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects.

PubMed

Rydén, Mikael; Andersson, Daniel P; Bernard, Samuel; Spalding, Kirsty; Arner, Peter

2013-10-01

Human obesity is associated with decreased triglyceride turnover and impaired lipolysis in adipocytes. We determined whether such defects also occur in subjects with only moderate increase in fat mass. Human abdominal subcutaneous adipose tissue was investigated in healthy, nonobese subjects [body mass index (BMI) > 17 kg/m(2) and BMI < 30 kg/m(2)]. Triglyceride age, reflecting lipid turnover, was examined in 41 subjects by assessing the incorporation of atmospheric (14)C into adipose lipids. Adipocyte lipolysis was examined as the ability of lipolytic agents to stimulate glycerol release in 333 subjects. Adipocyte triglyceride age was markedly increased in overweight (BMI ≥ 25 kg/m(2)) compared with lean subjects (P = 0.017) with triglyceride T1/2 of 14 and 9 months, respectively (P = 0.04). Triglyceride age correlated positively with BMI (P = 0.002) but not with adipocyte volume (P = 0.2). Noradrenaline-, isoprenaline- or dibutyryl cyclic AMP-induced lipolysis was inversely correlated with triglyceride age (P < 0.01) and BMI (P < 0.0001) independently of basal lipolysis, gender, and nicotine use. Current, but not the highest or lowest BMI in adult life, correlated significantly (inversely) with lipolysis. In conclusion, adipocyte triglyceride turnover and lipolytic activity are decreased in overweight subjects and reflect the current BMI status. These changes may confer an increased risk for early development and/or maintenance of excess body fat.

Glycogen Storage Disease Type Ia: Linkage of Glucose, Glycogen, Lactic Acid, Triglyceride, and Uric Acid Metabolism

PubMed Central

Sever, Sakine; Weinstein, David A.; Wolfsdorf, Joseph I.; Gedik, Reyhan; Schaefer, Ernst J.

2013-01-01

Case Summary A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides > 5,000 mg/dl. The diagnosis of type 1A glycogen storage disease (GSD) was made by liver biopsy that showed increased glycogen and absent glucose-6-phosphatase enzyme activity. She was treated with dextrose feeding, which was replaced by frequent cornstarch feeding, with improvement of her metabolic parameters. At age 18 years she had marked hypertriglyceridemia (3,860 mg/dl) and eruptive xanthomas, and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels > 75 mg/dl and lactate levels < 2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dl) off all medications were: total cholesterol 222, triglycerides 179, high density lipoprotein cholesterol 32, and calculated low density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m2. Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels > 75 mg/dl is critical in the management of this disease. PMID:23312056

Suicidal behaviour and lipid levels in unipolar and bipolar depression.

PubMed

Ainiyet, Babajohn; Rybakowski, Janusz K

2014-10-01

Evidence for a possible association between a low level of cholesterol and increased suicidal behaviour has accumulated in the recent 3 decades. The present study investigates whether lipid levels can make state-dependent markers of suicidal behaviour in Polish patients with mood disorder recently admitted to a psychiatric hospital owing to an acute depressive episode. The study was conducted on 223 patients (73 male and 150 female) with unipolar (n=171) and bipolar (n=52) depression. They were interviewed to assess any occurrence of suicidal thoughts, suicidal tendencies and/or suicidal attempts during the 3 months before admission. Laboratory measurements [total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and total lipids] were obtained within 24-72 h after hospital admission. Suicidal thoughts, tendencies, and attempts were associated with low total cholesterol, LDL cholesterol, and total lipids in both male and female patients, in both diagnostic categories. Triglycerides were significantly lower in male and female patients with suicidal thoughts compared with their non-suicidal counterparts. No association with suicidality was found with HDL cholesterol. The results of our study support a majority of research showing the association in depressed patients between suicidal behaviour and low levels of total and LDL cholesterol. In addition, the data suggest a similar association with low total lipids, and in some instances, with low triglycerides.

The combined action of omega-3 polyunsaturated fatty acids and grape proanthocyanidins on a rat model of diet-induced metabolic alterations.

PubMed

Ramos-Romero, Sara; Molinar-Toribio, Eunice; Pérez-Jiménez, Jara; Taltavull, Núria; Dasilva, Gabriel; Romeu, Marta; Medina, Isabel; Torres, Josep Lluís

2016-08-10

It has been suggested that food components such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and (poly)phenols counteract diet-induced metabolic alterations by common or complementary mechanisms. To examine the effects of a combination of ω-3 PUFAs and (poly)phenols on such alterations, adult Wistar-Kyoto rats were fed an obesogenic high-fat high-sucrose diet supplemented, or not, for 24 weeks with: eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) 1 : 1 (16.6 g kg(-1) feed); proanthocyanidin-rich grape seed extract (GSE, 0.8 g kg(-1) feed); or EPA/DHA 1 : 1 + GSE. Body weight, feed intake, and plasma glucose were evaluated every 6 weeks, while adipose tissue weight, insulin, glucagon, ghrelin, leptin, adiponectin, cholesterol, and triglycerides were evaluated at the end of the experiment. ω-3 PUFAs reduced plasma leptin and cholesterol levels, but did not modify diet-induced perigonadal fat or plasma insulin levels; while GSE increased plasma triglyceride levels. The combined action of ω-3 PUFAs and the proanthocyanidins reduced plasma insulin and leptin, as well as partially prevented perigonadal fat accumulation. While separate supplementation with ω-3 PUFAs or grape proanthocyanidins may not counteract all the key metabolic changes induced by a high-energy-dense diet, the combination of both supplements reverts altered insulin, leptin and triglyceride levels to normal.

Exercise effects on fitness, lipids, glucose tolerance and insulin levels in young adults.

PubMed

Israel, R G; Davidson, P C; Albrink, M J; Krall, J M

1981-07-01

The effect of 3 different physical training programs on cardiorespiratory (cr) fitness, fasting plasma lipids, glucose and insulin levels, and scapular skinfold thickness was assessed in 64 healthy college men. Training sessions were held 4 times a week for 5 weeks. The cr fitness improved significantly and skinfold thickness decreased following the aerobic, the pulse workout (interval training), and the anaerobic training compared to the control group. Skinfold thickness, plasma insulin, and triglyceride concentrations were significantly intercorrelated before and after training. The exercise programs had no significant effect on plasma cholesterol, triglycerides, phospholipids, glucose tolerance, or insulin levels. Change in adipose mass was thus dissociated from change in plasma insulin and triglyceride concentrations. It was concluded that in young men plasma triglycerides, the lipid component mostly readily reduced by exercise, were too low to be reduced further by a physical training program.

Effect of metformin and rosiglitazone on lipid metabolism in HIV infected patients receiving protease inhibitor containing HAART.

PubMed

Tomazic, Janez; Karner, Primoz; Vidmar, Ludvik; Maticic, Mojca; Sharma, Prem M; Janez, Andrej

2005-09-01

Insulin resistance may be the primary event in the protease inhibitor-associated metabolic syndrome. Treatment with insulin sensitizers (metformin, rosiglitazone) can ameliorate insulin resistance. So far, the effects of these agents on blood lipids have not been well determined. The aim of the present study was to evaluate the effects of metformin and rosiglitazone treatment on lipid metabolism in HIV infected patients receiving protease inhibitors containing HAART. HIV infected male patients (>18 years) were eligible for the study if they had impaired glucose tolerance with insulin resistance, characterized by fasting insulin concentration greater then 20 mIU/L and if they were on stable antiretroviral therapy regimen including a protease inhibitor for at least 12 months prior to the study enrolment. The patients were randomly assigned to receive either 1g/day metformin (metformin group, n=30) or 4 mg/day rosiglitazone maleate (rosiglitazone group, n=30) or no treatment (control group, n=30). The primary efficacy parameters were fasting plasma lipids, glucose levels and fasting insulin levels compared between baseline and week 48, by treatment groups. The total cholesterol concentration in rosiglitazone group increased from 5.76 -/+1.2 to 7.1-/+1.6 mmol/l (23% increase, p<0.05), HDL levels increased from 0.91-/+0.44 to 1.3-/+0.2 (38% increase, p<0.01) and LDL levels increased from 3.5-/+0.98 to 4.5-/+1.0 (28% increase, p<0.05). Treatment with metformin had no significant effect on total, HDL and LDL cholesterol. After 48 weeks of treatment, the fasting triglycerides concentration in the metformin group declined from 4.1-/+1.6 to 3.2-/+1.3 mmol/l (22% decrease,p<0.05) but in the rosiglitazone group no statistically significant effect on plasma triglycerides was noted. Furthermore, after 48 weeks of treatment the fasting insulin concentration in the rosiglitazone group declined by 49% and in the metformin group by 28%. This improvement in insulin secretion could be clearly demonstrated when the sums of insulin concentrations after oral glucose tolerance test were compared: 548-/+13 to 345-/+11.8 mIU/l in the rosiglitazone group (37% decrease, p<0.01) and from 552-/+15 to 420-/+12 mIU/l in the metformin group (24% decrease, p<0.01). The study demonstrates that both therapies improve insulin resistance. However, treatment with metformin has no effect on total, HDL and LDL cholesterol, but significantly reduces triglycerides, which has beneficial effect on the lipid status in these patients. Rosiglitazone causes significant increases in total cholesterol, HDL and LDL, but has no effect on triglycerides concentrations.

Association of Socioeconomic Status Measured by Education and Risk Factors for Carotid Atherosclerosis: Cross-sectional Study

PubMed Central

Maksimović, Miloš Ž.; Vlajinac, Hristina D.; Radak, Đorđe J.; Maksimović, Jadranka M.; Marinković, Jelena M.; Jorga, Jagoda B.

2008-01-01

Aim To investigate the association between socioeconomic status and metabolic syndrome, lifestyle, clinical and biochemical characteristics, and inflammatory markers as risk factors for carotid atherosclerotic disease. Methods This cross-sectional study, involving 657 consecutive patients with verified carotid atherosclerotic disease, was performed in Belgrade, Serbia, during the period 2006-2007. Formal education level was used as a proxy for socioeconomic status. Anthropometric parameters and data on cardiovascular risk factors were analyzed in participants with different levels of education – low (≤primary school), medium (secondary school), and high (university education). In the analysis, univariate and multivariate logistic regressions were used. Results Multivariate analysis showed that low education was significantly positively associated with female sex (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.45-3.81), increased triglycerides (OR, 1.79; 95% CI, 1.12-2.78), increased high-sensitivity C-reactive protein (hsCRP) (OR, 3.53; 95% CI, 2.17-5.88), and physical inactivity (OR, 4.24; 95% CI, 1.82-9.86) and negatively associated with former smoking (OR, 0.42; 95% CI, 0.23-0.75). Medium education was significantly positively associated with increased triglycerides (OR, 1.73; 95% CI, 1.14-2.62) and increased hsCRP (OR, 2.17; 95% CI, 1.37-3.41), and negatively with age (OR, 0.97; 95% CI, 0.94-0.99). Conclusion Increased triglycerides and hsCRP in people with low and medium education, and high prevalence of metabolic syndrome, its components and inflammatory markers in all study participants, suggest that regular health check-up, especially for those with lower education, may be useful in early detection and treatment of any abnormality that can be associated with cardiovascular disease. PMID:19090608

Association of socioeconomic status measured by education and risk factors for carotid atherosclerosis: cross-sectional study.

PubMed

Maksimović, Milos Z; Vlajinac, Hristina D; Radak, Dorde J; Maksimović, Jadranka M; Marinković, Jelena M; Jorga, Jagoda B

2008-12-01

To investigate the association between socioeconomic status and metabolic syndrome, lifestyle, clinical and biochemical characteristics, and inflammatory markers as risk factors for carotid atherosclerotic disease. This cross-sectional study, involving 657 consecutive patients with verified carotid atherosclerotic disease, was performed in Belgrade, Serbia, during the period 2006-2007. Formal education level was used as a proxy for socioeconomic status. Anthropometric parameters and data on cardiovascular risk factors were analyzed in participants with different levels of education--low (< or = primary school), medium (secondary school), and high (university education). In the analysis, univariate and multivariate logistic regressions were used. Multivariate analysis showed that low education was significantly positively associated with female sex (odds ratio [OR], 2.38; 95% confidence interval [CI], 1.45-3.81), increased triglycerides (OR, 1.79; 95% CI, 1.12-2.78), increased high-sensitivity C-reactive protein (hsCRP) (OR, 3.53; 95% CI, 2.17-5.88), and physical inactivity (OR, 4.24; 95% CI, 1.82-9.86) and negatively associated with former smoking (OR, 0.42; 95% CI, 0.23-0.75). Medium education was significantly positively associated with increased triglycerides (OR, 1.73; 95% CI, 1.14-2.62) and increased hsCRP (OR, 2.17; 95% CI, 1.37-3.41), and negatively with age (OR, 0.97; 95% CI, 0.94-0.99). Increased triglycerides and hsCRP in people with low and medium education, and high prevalence of metabolic syndrome, its components and inflammatory markers in all study participants, suggest that regular health check-up, especially for those with lower education, may be useful in early detection and treatment of any abnormality that can be associated with cardiovascular disease.

Dietary selenium disrupts hepatic triglyceride stores and transcriptional networks associated with growth and Notch signaling in juvenile rainbow trout.

PubMed

Knight, Rosalinda; Marlatt, Vicki L; Baker, Josh A; Lo, Bonnie P; deBruyn, Adrian M H; Elphick, James R; Martyniuk, Christopher J

2016-11-01

Dietary Se has been shown to adversely affect adult fish by altering growth rates and metabolism. To determine the underlying mechanisms associated with these observations, we measured biochemical and transcriptomic endpoints in rainbow trout following dietary Se exposures. Treatment groups of juvenile rainbow trout were fed either control Lumbriculus variegatus worms or worms cultured on selenized yeast. Selenized yeast was cultured at four nominal doses of 5, 10, 20 or 40mg/kg Se dry weight (measured dose in the worms of 7.1, 10.7, 19.5, and 31.8mg/kgSedw respectively) and fish were fed for 60days. At 60 d, hepatic triglycerides, glycogen, total glutathione, 8-isoprostane and the transcriptome response in the liver (n=8/group) were measured. Fish fed the nominal dose of 20 and 40mg/kg Se dry weight had lower body weight and a shorter length, as well as lower triglyceride in the liver compared to controls. Evidence was lacking for an oxidative stress response and there was no change in total glutathione, 8-isoprostane levels, nor relative mRNA levels for glutathione peroxidase isoforms among groups. Microarray analysis revealed that molecular networks for long-chain fatty acid transport, lipid transport, and low density lipid oxidation were increased in the liver of fish fed 40mg/kg, and this is hypothesized to be associated with the lower triglyceride levels in these fish. In addition, up-regulated gene networks in the liver of 40mg/kg Se treated fish included epidermal growth factor receptor signaling, growth hormone receptor, and insulin growth factor receptor 1 signaling pathways. These molecular changes are hypothesized to be compensatory and related to impaired growth. A gene network related to Notch signaling, which is involved in cell-cell communication and gene transcription regulation, was also increased in the liver following dietary treatments with both 20 and 40mg/kg Se. Transcriptomic data support the hypothesis that dietary Se increases the expression of networks for growth-related signaling cascades in addition to those related to fatty acid synthesis and metabolism. We propose that the disruption of metabolites related to triglyceride processing and storage, as well as gene networks for epidermal growth factor and Notch signaling in the liver, represent key molecular initiating events for adverse outcomes related to growth and Se toxicity in fish. Copyright © 2016 Elsevier B.V. All rights reserved.

Antioxidant and triglyceride-lowering effects of vitamin E associated with the prevention of abnormalities in the reactivity and morphology of aorta from streptozotocin-diabetic rats. Antioxidants in Diabetes-Induced Complications (ADIC) Study Group.

PubMed

Karasu, C; Ozansoy, G; Bozkurt, O; Erdoğan, D; Omeroğlu, S

1997-08-01

In this study, we evaluated the effects of vitamin E on the vascular reactivity and structure of thoracic aorta from streptozotocin (STZ)-diabetic rats. Plasma glucose, cholesterol, and triglyceride concentrations in rats were increased markedly by STZ-diabetes. The thiobarbituric acid (TBA) reactivity level as an index of lipid peroxidation was higher in both plasma and aorta of STZ-diabetic rats compared with controls. The rings of thoracic aorta with or without endothelium were mounted in organ chambers for measurement of isometric tension and were contracted by a single dose (10-5 mol/L) and then cumulative doses of noradrenaline ([NA] 10(-9) to 10(-5) mol/L). Pretreatment with methylene blue (MB) or removal of the endothelium resulted in a similar degree of enhancement in NA-induced contraction of control rings. STZ-diabetes increased the fast and slow components of NA-induced contraction in all experiments. The maximal contractile response of aorta to NA was also augmented by STZ-diabetes, whereas the sensitivity (pD2) remained unaltered. STZ-diabetes resulted in significant increases in the maximum contractile response and sensitivity of aorta to KCl. STZ-diabetic rats showed a significant reduction in the percentage of endothelial response (PER). A group of diabetic rats was treated from the time of diabetes induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned plasma triglycerides toward normal levels. Diabetes-induced abnormal contractility and endothelial dysfunction were significantly but not completely prevented by vitamin E treatment. The endothelium-independent relaxation response to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E treatment. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E treatment can protect the morphological integrity of aorta against STZ-diabetes. The results suggest the following: (1) The increased triglycerides/lipid peroxides may be an important reason for morphological or functional disruption of endothelium and enhanced activation of contractile mechanisms of vascular smooth muscle in STZ-diabetic rats. Both contribute to an increased responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E treatment of STZ-diabetic rats can prevent the development of abnormal contractility and structure and endothelial dysfunction in aorta. (3) The triglyceride- and/or lipid peroxidation-lowering effect of vitamin E may be crucial for the protective effect of this vitamin on the vasculature.

Fasting upregulates adipose triglyceride lipase and hormone-sensitive lipase levels and phosphorylation in mouse kidney.

PubMed

Marvyn, Phillip M; Bradley, Ryan M; Button, Emily B; Mardian, Emily B; Duncan, Robin E

2015-06-01

Circulating non-esterified fatty acids (NEFA) rise during fasting and are taken up by the kidneys, either directly from the plasma or during re-uptake of albumin from glomerular filtrate, and are stored as triacylglycerol (TAG). Subsequent utilization of stored fatty acids requires their hydrolytic release from cellular lipid droplets, but relatively little is known about renal lipolysis. We found that total [(3)H]triolein hydrolase activity of kidney lysates was significantly increased by 15% in the fasted state. Adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) mRNA expression was time-dependently increased by fasting, along with other fatty acid metabolism genes (Pparα, Cd36, and Aox). ATGL and HSL protein levels were also significantly induced (by 239 ± 7% and 322 ± 8%, respectively). Concomitant with changes in total protein levels, there was an increase in ATGL phosphorylation at the AMPK-regulated serine 406 site in the 14-3-3 binding motif, and an increase in HSL phosphorylation at serines 565 and 660 that are regulated by AMPK and PKA, respectively. Using immunofluorescence, we further demonstrate nearly ubiquitous expression of ATGL in the renal cortex with a concentration on the apical/lumenal surface of some cortical tubules. Our findings suggest a role for ATGL and HSL in kidney lipolysis.

Atorvastatin and fenofibrate increase apolipoprotein AV and decrease triglycerides by up-regulating peroxisome proliferator-activated receptor-α

PubMed Central

Huang, Xian-sheng; Zhao, Shui-ping; Bai, Lin; Hu, Min; Zhao, Wang; Zhang, Qian

2009-01-01

Background and purpose: Combining statin and fibrate in clinical practice provides a greater reduction of triglycerides than either drug given alone, but the mechanism for this effect is poorly understood. Apolipoprotein AV (apoAV) has been implicated in triglyceride metabolism. This study was designed to investigate the effect of the combination of statin and fibrate on apoAV and the underlying mechanism(s). Experimental approach: Hypertriglyceridaemia was induced in rats by giving them 10% fructose in drinking water for 2 weeks. They were then treated with atorvastatin, fenofibrate or the two agents combined for 4 weeks, and plasma triglyceride and apoAV measured. We also tested the effects of these two agents on triglycerides and apoAV in HepG2 cells in culture. Western blot and reverse transcription polymerase chain reaction was used to measure apoAV and peroxisome proliferator-activated receptor-α (PPARα) expression. Key results: The combination of atorvastatin and fenofibrate resulted in a greater decrease in plasma triglycerides and a greater increase in plasma and hepatic apoAV than either agent given alone. Hepatic expression of the PPARα was also more extensively up-regulated in rats treated with the combination. A similar, greater increase in apoAV and a greater decrease in triglycerides were observed following treatment of HepG2 cells pre-exposed to fructose), with the combination. Adding an inhibitor of PPARα (MK886) abolished the effects of atorvastatin on HepG2 cells. Conclusions and implications: A combination of atorvastatin and fenofibrate increased apoAV and decreased triglycerides through up-regulation of PPARα. PMID:19694729

Medium chain triglycerides and hepatic encephalopathy

PubMed Central

Morgan, M. Hilary; Bolton, C. H.; Morris, J. S.; Read, A. E.

1974-01-01

The oral administration of short (C6) and medium (C8 and (C10) chain triglycerides produced no clinical or electroencephalographic changes in patients with cirrhosis of the liver. Arterial ammonia levels were also monitored in these patients and showed no significant change after medium chain triglycerides. It was concluded that medium chain triglycerides, known to be of potential value in the treatment of malabsorption in patients with cirrhosis, are not clinically contraindicated, even in patients with evidence of hepatic encephalopathy. PMID:4841275

Consumption of whole grains and legumes modulates the genetic effect of the APOA5 -1131C variant on changes in triglyceride and apolipoprotein A-V concentrations in patients with impaired fasting glucose or newly diagnosed type 2 diabetes

PubMed Central

2014-01-01

Background The apolipoprotein A5 gene (APOA5) -1131 T > C polymorphism is associated with mild hypertriglyceridemia in type 2 diabetic subjects, and interacts with dietary fat in the determination of triglyceride concentrations. We examined whether a substitution of whole grains and legumes for refined rice in a high carbohydrate diet (about 65% of energy derived from carbohydrate) may modify the effect of this variant on changes in apolipoprotein A-V (apoA-V) and triglyceride concentrations. Methods We genotyped the APOA5 -1131 T > C in individuals with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes, who were randomly assigned to either a group ingesting whole grain and legume meals daily or a control group for 12 weeks. Results After dietary intervention, we observed significant interactions between the APOA5 -1131 T > C polymorphism and carbohydrate sources (whole grains and legumes versus refined rice) in the determination of mean percent changes in triglyceride and apoA-V (P interactions <0.001 and =0.038, respectively). In the refined rice group (n = 93), the carriers of the risk C allele (n = 50) showed a greater increase in the mean percent changes of triglyceride and apoA-V than noncarriers after adjusting for HOMA-IR (P = 0.004 and 0.021, respectively). The whole grain and legume group (n = 92), however, showed a decrease in fasting glucose, HOMA-IR, and triglyceride, and an increase in apoA-V, irrespective of genotype. Conclusions The data showed that the magnitude of the genetic effect of the APOA5 -1131C variant on triglyceride and apoA-V levels was modulated when substituting consumption of whole grains and legumes for refined rice as a carbohydrate source in IFG or diabetic subjects. Trial registration ClinicalTrials.gov: NCT01784952. PMID:24690159

Night work is associated with glycemic levels and anthropometric alterations preceding diabetes: Baseline results from ELSA-Brasil.

PubMed

Silva-Costa, Aline; Rotenberg, Lucia; Coeli, Claudia Medina; Nobre, Aline Araújo; Griep, Rosane Härter

2016-01-01

Night work has been suggested as a risk factor for diabetes. Individuals with high triglyceride levels, high LDL cholesterol, low HDL cholesterol and obesity, especially abdominal obesity, have a greater chance of developing diabetes. The aim of this study was to analyze glycemic levels, total cholesterol, HDL-C, LDL-C, triglycerides and the anthropometric alterations that precede diabetes, considering their possible association with nigh work among a non-diabetic population. Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) comprises of 15,105 civil servants (35-74 years old) at baseline (2008-2010). The following parameters were analyzed: serum cholesterol (total cholesterol, HDL-C, LDL-C), triglycerides and glucose drawn from 12-hour fasting blood sample, glycated hemoglobin and 2-hour plasma glucose obtained after a 75 g oral glucose tolerance test, BMI, hip and waist measurements using standard equipment and techniques. Participants with diabetes, retired workers and day workers with previous experience of night work were excluded. Generalized linear models, a gamma regression model with an identity link function, were performed to test the association of night work with metabolic and anthropometric variables. The study sample consisted of 3918 men and 4935 women; 305 (7.8%) and 379 (7.7%) of the participants were men and women who worked at night, respectively. Among the men, the exposure to night work was associated with an increase in BMI (b-value = 0.542; p = 0.032) and waist circumference (b-value = 1.66; p = 0.014). For women, increased fasting plasma glucose (b-value = 2.278; p < 0.001), glycated hemoglobin (b-value = 0.099, p < 0.001) and 2 hour plasma glucose (b-value = 5.479, p = 0.001) were associated with night work after adjustments. No significant associations between night work and triglycerides, LDL-C, HDL-C, total cholesterol levels or waist-hip ratio were found. The influences of night work on metabolic and anthropometric factors suggest night work as a potential risk factor for type 2 diabetes. Further studies are needed to investigate the inconclusive data on gender differences in the associations.

Analysis of the effects of exposure to polychlorinated biphenyls and chlorinated pesticides on serum lipid levels in residents of Anniston, Alabama

PubMed Central

2013-01-01

Background Anniston, Alabama, is the site of a former Monsanto plant where polychlorinated biphenyls (PCBs) were manufactured from 1929 until 1971. Residents of Anniston are known to have elevated levels of PCBs. The objective of the study was to test the hypothesis that levels of the various lipid components (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) are differentially associated with concentrations of total PCBs and total pesticides, and further that different congeners, congener groups and different pesticides do not have identical associations in serum samples obtained from Anniston residents in a cross-sectional study. Methods Fasting serum samples were obtained from 575 residents of Anniston who were not on any lipid-lowering medication and were analyzed for 35 PCB congeners, nine chlorinated pesticides, total cholesterol, LDL and HDL cholesterol and triglyceride concentrations. Associations between toxicant concentrations and lipid levels were determined using multiple linear regression analysis. Results We observed that elevated serum concentrations of lipids were associated with elevated serum concentrations of ΣPCBs and summed pesticides in analyses adjusted for age, race, gender, BMI, alcohol consumption, smoking and exercising status. The strongest associations were seen for PCB congeners with three, four, or at least eight substituted chlorines. Mono-ortho substituted congeners 74 and 156, di-ortho congeners 172 and 194, and tri- and tetra-ortho congeners 199, 196–203, 206 and 209 each were significantly associated with total lipids, total cholesterol and triglycerides. Serum concentrations of HCB and chlordane also had strong associations with lipid components. Conclusions Increased concentrations of PCBs and organochlorine pesticides are associated with elevations in total serum lipids, total cholesterol and triglycerides, but the patterns are different for different groups of PCBs and different pesticides. These observations show selective effects of different organochlorines on serum concentrations of different groups of lipids. This elevation in concentrations of serum lipids may be the basis for the increased incidence of cardiovascular disease found in persons with elevated exposures to PCBs and chlorinated pesticides. PMID:24325314

The Choice of Euthanasia Method Affects Metabolic Serum Biomarkers.

PubMed

Pierozan, Paula; Jernerén, Fredrik; Ransome, Yusuf; Karlsson, Oskar

2017-08-01

The impact of euthanasia methods on endocrine and metabolic parameters in rodent tissues and biological fluids is highly relevant for the accuracy and reliability of the data collected. However, few studies concerning this issue are found in the literature. We compared the effects of three euthanasia methods currently used in animal experimentation (i.e. decapitation, CO 2 inhalation and pentobarbital injection) on the serum levels of corticosterone, insulin, glucose, triglycerides, cholesterol and a range of free fatty acids in rats. The corticosterone and insulin levels were not significantly affected by the euthanasia protocol used. However, euthanasia by an overdose of pentobarbital (120 mg/kg intraperitoneal injection) increased the serum levels of glucose, and decreased cholesterol, stearic and arachidonic acids levels compared with euthanasia by CO 2 inhalation and decapitation. CO 2 inhalation appears to increase the serum levels of triglycerides, while euthanasia by decapitation induced no individual discrepant biomarker level. We conclude that choice of the euthanasia methods is critical for the reliability of serum biomarkers and indicate the importance of selecting adequate euthanasia methods for metabolic analysis in rodents. Decapitation without anaesthesia may be the most adequate method of euthanasia when taking both animal welfare and data quality in consideration. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Maternal lipids in pregnancy are associated with increased offspring cortisol reactivity in childhood.

PubMed

Mina, Theresia H; Lahti, Marius; Drake, Amanda J; Forbes, Shareen; Denison, Fiona C; Räikkönen, Katri; Norman, Jane E; Reynolds, Rebecca M

2017-09-01

Prenatal programming of hypothalamic-pituitary-adrenal (HPA) axis activity has long term implications for offspring health. Biological mechanisms underlying programming of the offspring HPA axis are poorly understood. We hypothesised that altered maternal metabolism including higher maternal obesity, glucose and lipids are novel programming factors for altered offspring HPA axis activity. Salivary cortisol levels were measured in 54 children aged 3-5 years under experimental conditions (before and after a delay of self-gratification test). Associations of child cortisol responses with maternal obesity in early pregnancy and with fasting glucose, triglycerides, HDL and total cholesterol measured in each pregnancy trimester were tested. Higher levels of maternal triglycerides and total cholesterol throughout pregnancy were associated with increased offspring cortisol reactivity. The associations were independent of maternal obesity and other confounders, suggesting that exposure to maternal lipids could be a biological mechanism of in utero programming of the offspring's HPA axis. Copyright © 2017. Published by Elsevier Ltd.

Pregnancies in Glycogen Storage Disease Type Ia

PubMed Central

Martens, Daniëlle HJ; Rake, Jan Peter; Schwarz, Martin; Ullrich, Kurt; Weinstein, David A; Merkel, Martin; Sauer, Pieter JJ; Smit, G Peter A

2013-01-01

Objective Reports on pregnancies in women with GSD-Ia are scarce. Due to improved life expectancy, pregnancy is becoming an important issue. We describe 15 pregnancies focusing on dietary treatment, biochemical parameters and GSD-Ia complications. Study Design Carbohydrate requirements (mg/kg/min), triglyceride and uric acid levels, liver ultrasonography and creatinine clearance were investigated before, during and after pregnancy. Data of the newborns were obtained from the records. Results In the first trimester, a significant increase in carbohydrate requirements was observed (p=0,007). Most patients had acceptable triglyceride and uric acid levels during pregnancy. No increase in size/number of adenomas was seen. In 3/4 patients, a decrease in GFR was observed after pregnancy. In three pregnancies, lactic acidosis developed during delivery with severe multi-organ failure in one. All but one of the children are healthy and show good psychomotor development. Conclusion Successful pregnancies are possible in GSD-Ia patients, although specific GSD-Ia related risks are present. PMID:18241814

Cumulative increased risk of incident type 2 diabetes mellitus with increasing triglyceride glucose index in normal-weight people: The Rural Chinese Cohort Study.

PubMed

Zhang, Ming; Wang, Bingyuan; Liu, Yu; Sun, Xizhuo; Luo, Xinping; Wang, Chongjian; Li, Linlin; Zhang, Lu; Ren, Yongcheng; Zhao, Yang; Zhou, Junmei; Han, Chengyi; Zhao, Jingzhi; Hu, Dongsheng

2017-03-01

Risk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China. We included data from 5706 people with normal body mass index (BMI) (18.5-23.9 kg/m 2 ) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure-response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2]. Risk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20-5.11], 3.77 [1.83-7.79], and 5.30 [2.21-12.71], P trend  < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22-6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index. Risk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM.

The PPARα/γ dual agonist chiglitazar improves insulin resistance and dyslipidemia in MSG obese rats

PubMed Central

Li, Ping-Ping; Shan, Song; Chen, Yue-Teng; Ning, Zhi-Qiang; Sun, Su-Juan; Liu, Quan; Lu, Xian-Ping; Xie, Ming-Zhi; Shen, Zhu-Fang

2006-01-01

The aim of this study was to investigate the capacity of chiglitazar to improve insulin resistance and dyslipidemia in monosodium L-glutamate (MSG) obese rats and to determine whether its lipid-lowering effect is mediated through its activation of PPARα. Chiglitazar is a PPARα/γ dual agonist. The compound improved impaired insulin and glucose tolerance; decreased plasma insulin level and increased the insulin sensitivity index and decreased HOMA index. Euglycemic hyperinsulinemic clamp studies showed chiglitazar increased the glucose infusion rate in MSG obese rats. Chiglitazar inhibited alanine gluconeogenesis, lowered the hepatic glycogen level in MSG obese rats. Like rosiglitazone, chiglitazar promoted the differentiation of adipocytes and decreased the maximal diameter of adipocytes. In addition, chiglitazar decreased the fibrosis and lipid accumulation in the islets and increased the size of islets. Chiglitazar reduced plasma triglyceride, total cholesterol (TCHO), nonesterified fatty acids (NEFA) and low density lipoprotein-cholesterol levels; lowered hepatic triglyceride and TCHO contents; decreased muscular NEFA level. Unlike rosiglitazone, chiglitazar showed significant increase of mRNA expression of PPARα, CPT1, BIFEZ, ACO and CYP4A10 in the liver of MSG obese rats. These data suggest that PPARα/γ coagonist, such as chiglitazar, affect lipid homeostasis with different mechanisms from rosiglitazone, chiglitazar may have better effects on lipid homeostasis in diabetic patients than selective PPARγ agonists. PMID:16751799

Associations between apolipoprotein E genotypes and serum levels of glucose, cholesterol, and triglycerides in a cognitively normal aging Han Chinese population.

PubMed

Tao, Qing-Qing; Chen, Yan; Liu, Zhi-Jun; Sun, Yi-Min; Yang, Ping; Lu, Shen-Ji; Xu, Miao; Dong, Qin-Yun; Yang, Jia-Jun; Wu, Zhi-Ying

2014-01-01

To determine the associations between apolipoprotein E (APOE) genotypes and serum levels of glucose, total cholesterol, and triglycerides in a cognitively normal aging Han Chinese population. There were 1,003 cognitively normal aging subjects included in this study. APOE genotypes were analyzed and biochemical parameters were tested. All the subjects were divided into three groups according to APOE genotypes: (1) E2/2 or E2/3 (APOE E2); (2) E3/3 (APOE E3); and (3) E2/4, E3/4, or E4/4 (APOE E4). Correlations of serum levels of glucose, total cholesterol, and triglycerides with APOE genotypes were assessed. E2, E3, and E4 allele frequencies were found to be 6.2%, 82.1%, and 11.7%, respectively. Serum levels of total cholesterol were higher in the APOE E4 group (P<0.05). A higher level of total cholesterol was associated with the E4 allele (adjusted odds ratio 1.689, 95% confidence interval 1.223-2.334, P<0.01). However, no association was found between APOE status and serum levels of glucose (adjusted odds ratio 0.981, 95% confidence interval 0.720-1.336, P=0.903) or total triglycerides (adjusted odds ratio 1.042, 95% confidence interval 0.759-1.429, P=0.800). A higher serum level of total cholesterol was significantly correlated with APOE E4 status in a cognitively normal, nondiabetic aging population. However, there was no correlation between APOE genotypes and serum levels of glucose or total triglycerides.

The effect of olive oil-based ketogenic diet on serum lipid levels in epileptic children.

PubMed

Güzel, Orkide; Yılmaz, Unsal; Uysal, Utku; Arslan, Nur

2016-03-01

Ketogenic diet (KD) is one of the most effective therapies for intractable epilepsy. Olive oil is rich in monounsaturated fatty acids and antioxidant molecules and has some beneficial effects on lipid profile, inflammation and oxidant status. The aim of this study was to evaluate the serum lipid levels of children who were receiving olive oil-based KD for intractable seizures at least 1 year. 121 patients (mean age 7.45 ± 4.21 years, 57 girls) were enrolled. At baseline and post-treatment 1, 3, 6, and 12 months body mass index-SDS, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride levels were measured. Repeated measure ANOVA with post hoc Bonferroni correction was used for data analysis. The mean duration of KD was 15.4 ± 4.1 months. Mean total cholesterol, LDL-cholesterol and triglyceride levels were significantly higher at 1st, 3rd, 6th and 12th months of the KD treatment, compared to pre-treatment levels (p = 0.001), but showed no difference among during-treatment measurements. Mean body mass index-SDS and HDL-cholesterol levels were not different among the baseline and follow-up time points (p = 0.113 and p = 0.067, respectively). No child in this study discontinued the KD because of dyslipidemia. Even if rich in olive oil, high-fat KD causes significant increase in LDL-cholesterol and triglyceride levels. More studies are needed to determine the effect of KD on serum lipids in children using different fat sources in the diet.

Therapeutic role of Cuminum cyminum on ethanol and thermally oxidized sunflower oil induced toxicity.

PubMed

Aruna, K; Rukkumani, R; Varma, P Suresh; Menon, Venugopal P

2005-05-01

Ethanol is one of the most widely used and abused drugs, increasing lipid levels in humans and experimental animals. Heating of oil rich in polyunsaturated fatty acids (PUFA) produces various lipid peroxidative end products that can aggravate the pathological changes produced by ethanol. In the present communication, the effect of Cuminum cyminum was investigated on alcohol and thermally oxidized oil induced hyperlipidaemia. The results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides and phospholipids in the plasma of rats given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in rats groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats. The levels were decreased when cumin was given along with alcohol and thermally oxidized oil. The level of phospholipids decreased significantly in the liver and kidney of groups given alcohol, thermally oxidized oil and alcohol+thermally oridized oil when compared with the normal control rats. The level increased when cumin was administered along with alcohol and thermally oxidized oil. The activity of phospholipase A and C increased significantly in the liver of groups given alcohol, thermally oxidized oil and alcohol+thermally oxidized oil when compared with the normal control rats, whereas the activity was decreased with the cumin treatment. The results obtained indicate that cumin can decrease the lipid levels in alcohol and thermally oxidized oil induced hepatotoxicity. Copyright (c) 2005 John Wiley & Sons, Ltd.

Effects of a Novel Nutritional Formula Enriched With Eicosapentaenoic Acid and Docosahexaenoic Acid Specially Developed for Tube-Fed Hemodialysis Patients.

PubMed

Esaki, Shinga; Iwahori, Motokazu-Tohru; Takagi, Yuri; Wada, Toshikazu; Morita, Shunsuke; Sonoki, Hirofumi; Nakao, Toshiyuki

2017-03-01

To evaluate the effects of a nutritional formula enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in tube-fed bedridden hemodialysis patients. A prospective, multicenter, single-arm study. Koyukai Memorial Hospital, Orimoto Hospital, and Chofu Hospital, Japan. Eleven tube-fed bedridden hemodialysis patients. Patients were fed a nutritional formula enriched with EPA and DHA for 12 weeks. Body weight; body mass index (BMI); serum levels of total protein, albumin, prealbumin, total cholesterol, triglyceride, and C-reactive protein (CRP); serum fatty acid composition. Body weight; BMI; and serum levels of total protein, albumin, total cholesterol, triglyceride, and CRP at 12 weeks were not significantly different from baseline levels. Serum prealbumin, EPA, and DHA levels significantly increased after 12 weeks of treatment. A nutritional formula enriched with EPA and DHA may be beneficial for nutritional management in tube-fed bedridden hemodialysis patients. Copyright © 2016. Published by Elsevier Inc.

Targeted delivery of HGF to the skeletal muscle improves glucose homeostasis in diet-induced obese mice.

PubMed

Sanchez-Encinales, Viviana; Cozar-Castellano, Irene; Garcia-Ocaña, Adolfo; Perdomo, Germán

2015-12-01

Hepatocyte growth factor (HGF) is a cytokine that increases glucose transport ex vivo in skeletal muscle. The aim of this work was to decipher the impact of whether conditional overexpression of HGF in vivo could improve glucose homeostasis and insulin sensitivity in mouse skeletal muscle. Following tetracyclin administration, muscle HGF levels were augmented threefold in transgenic mice (SK-HGF) compared to control mice without altering plasma HGF levels. In conditions of normal diet, SK-HGF mice showed no differences in body weight, plasma triglycerides, blood glucose, plasma insulin and glucose tolerance compared to control mice. Importantly, obese SK-HGF mice exhibited improved whole-body glucose tolerance independently of changes in body weight or plasma triglyceride levels compared to control mice. This effect on glucose homeostasis was associated with significantly higher (∼80%) levels of phosphorylated protein kinase B in muscles from SK-HGF mice compared to control mice. In conclusion, muscle expression of HGF counteracts obesity-mediated muscle insulin resistance and improves glucose tolerance in mice.

Effects of parental hypertension on longitudinal trends in blood pressure and plasma metabolic profile: mixed-effects model analysis.

PubMed

Mitsumata, Kaneto; Saitoh, Shigeyuki; Ohnishi, Hirofumi; Akasaka, Hiroshi; Miura, Tetsuji

2012-11-01

The mechanism underlying the association of parental hypertension with cardiovascular events in offspring remains unclear. In this study, the effects of parental hypertension on longitudinal trends of blood pressure and metabolic parameters were examined by mixed-effects model analysis. From 1977 to 2006, 5198 subjects participated in the Tanno-Sobetsu Study, and we selected 2607 subjects (1095 men and 1512 women) for whom data on parental history of hypertension were available. In both men and women with and without parental hypertension, systolic blood pressure and fasting blood glucose levels consistently increased from the third to eighth decades of life, whereas diastolic blood pressure and serum triglyceride levels followed biphasic (inverted U shape) time courses during that period. However, the relationships between the parameters and age were significantly shifted upward (by ≈5.3 mm Hg in systolic blood pressure, 2.8 mm Hg in diastolic blood pressure, 0.30 mmol/L in blood glucose, and 0.09 mmol/L in triglyceride) in the group with parental hypertension compared with those in the group without parental hypertension. Both paternal and maternal histories of hypertension were determinants of systolic blood pressure and diastolic blood pressure, and there was no significant interaction between the sides of parental history. There were no significant effects of parental hypertension on age-dependent or body mass index-dependent changes in serum low-density lipoprotein cholesterol or high-density lipoprotein cholesterol level. The present results indicate that parental hypertension has an age-independent impact on elevation of blood pressure, plasma glucose, and triglyceride levels, which may underlie the reported increase in cardiovascular events by family history of hypertension.

Gut Microbiota and Metabolic Endotoxemia in Young Obese Mexican Subjects

PubMed Central

Radilla-Vázquez, Romina Belén; Parra-Rojas, Isela; Martínez-Hernández, Norma Edith; Márquez-Sandoval, Yolanda Fabiola; Illades-Aguiar, Berenice; Castro-Alarcón, Natividad

2016-01-01

Background The gut microbiota plays an important role in human metabolism; previous studies suggest that the imbalance can cause a metabolic endotoxemia that may be linked to weight gain and insulin resistance. The purpose of this study was to investigate the relationship between the gut microbiota composition, the lipopolysaccharide levels and the metabolic profile in obese and normal-weight young subjects. Methods We studied 32 obese (BMI ≥ 30 kg/m2) and 32 normal-weight subjects (BMI = 18.5-24.9 kg/m2), aged 18-25 years. Quantification of intestinal bacteria was performed by real-time PCR. Endotoxin units were determined with the test QCL-1000, and biochemical profile was performed under a standard protocol of Spinreact. Results Obese individuals had a BMI of 34.5 (32.9-36.45) kg/m2, increased triglycerides (123 vs. 70 mg/dl), total cholesterol (168 vs. 142 mg/dl), and LDL-cholesterol (114 vs. 96.5 mg/dl). In obese subjects body temperature was higher than in normal-weight subjects. We found a greater number of Clostridum leptum and Lactobacillus (p < 0.001) and lower numbers of Prevotella and Escherichia coli (p < 0.001) in the obese group. A decrease of E. coli was associated with an increased risk of lipopolysaccharide levels ranging from 1 to 1.3 EU/ml. A positive correlation was found between serum lipopolysaccharides and BMI (r = 0.46, p = 0.008), triglyceride levels (r = 0.44, p = 0.011) as well as waist circumference (r = 0.34, p = 0.040), being more evident in young obese females. Conclusion Subclinical metabolic endotoxemia determined by serum concentration of lipopolysaccharides was related to the smallest amount of E. coli, high triglyceride levels, and central adiposity in obese young persons. PMID:26745497

Effect of Guava in Blood Glucose and Lipid Profile in Healthy Human Subjects: A Randomized Controlled Study

PubMed Central

Rakavi, R; Mangaraj, Manaswini

2016-01-01

Introduction The fruit of Psidium guajava (P.guajava) is known to contain free sugars yet the fruit juice showed hypoglycaemic effect. Hypoglycaemic activity of guava leaves has been well documented but not for guava fruit. Aim So we aimed to evaluate the effect of ripe guava (with peel and without peel) fruit supplementation on blood glucose and lipid profile in healthy human subjects. Materials and Methods Randomized Controlled study undertaken in: 1) Baseline; 2) 6 weeks supplementation phase. Forty five healthy MBBS students were included and randomly enrolled into Group A, Group B and Group C. In Baseline phase: Fasting Plasma Glucose (FPG) and serum lipid profile was done in all 3 groups. Group A were supplemented with 400g of ripe guava with peel and group B without peel, for 6 weeks. Rest 15 treated as control i.e., Group C. Result Supplementation of ripe guava fruit with peel reduced BMI as well as blood pressure (p<0.05) in group A, whereas the FPG, Total cholesterol, Triglycerides were found significantly increased (p<0.05). Group B registered a significant fall (p<0.05) in BMI as well as blood pressure. Fall in FPG level after guava pulp supplementation was not significant. Serum Total cholesterol, Triglycerides and Low Density Lipoprotein Cholesterol (LDLc) levels decreased significantly (p<0.05) indicating that guava pulp without peel may have a favourable effect on lipid levels and blood sugar as well. Conclusion Guava fruit without peel is more effective in lowering blood sugar as well as serum total cholesterol, triglycerides and LDLc. It increases HDLc levels also. PMID:27790420

In vitro antioxidant and antihyperlipidemic activities of Bauhinia variegata Linn

PubMed Central

Rajani, G.P.; Ashok, Purnima

2009-01-01

Objectives: To evaluate the ethanolic and aqueous extracts of Bauhinia variegata Linn. for in vitro antioxidant and antihyperlipidemic activity. Materials and Methods: Ethanolic and aqueous extracts of the stem bark and root of B. variegata Linn. were prepared and assessed for in vitro antioxidant activity by various methods namely total reducing power, scavenging of various free radicals such as 1,2-diphenyl-2-picrylhydrazyl (DPPH), super oxide, nitric oxide, and hydrogen peroxide. The percentage scavenging of various free radicals were compared with standard antioxidants such as ascorbic acid and butylated hydroxyl anisole (BHA). The extracts were also evaluated for antihyperlipidemic activity in Triton WR-1339 (iso-octyl polyoxyethylene phenol)-induced hyperlipidemic albino rats by estimating serum triglyceride, very low density lipids (VLDL), cholesterol, low-density lipids (LDL), and high-density lipid (HDL) levels. Result: Significant antioxidant activity was observed in all the methods, (P < 0.01) for reducing power and (P < 0.001) for scavenging DPPH, super oxide, nitric oxide, and hydrogen peroxide radicals. The extracts showed significant reduction (P < 0.01) in cholesterol at 6 and 24 h and (P < 0.05) at 48 h. There was significant reduction (P < 0.01) in triglyceride level at 6, 24, and 48 h. The VLDL level was also significantly (P < 0.05) reduced from 24 h and maximum reduction (P < 0.01) was seen at 48 h. There was significant increase (P < 0.01) in HDL at 6, 24, and 48 h. Conclusion: From the results, it is evident that alcoholic and aqueous extracts of B. variegata Linn. can effectively decrease plasma cholesterol, triglyceride, LDL, and VLDL and increase plasma HDL levels. In addition, the alcoholic and aqueous extracts have shown significant antioxidant activity. By the virtue of its antioxidant activity, B. variegata Linn. may show antihyperlipidemic activity. PMID:20177495

Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

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

Ma, Noelle; Department of Obstetrics and Gynecology, The University of Western Ontario; The Lawson Health Research Institute, The University of Western Ontario

While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal daymore » 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced acetylation of histone H3 [K9,14]. • This provides a mechanism for developmental origins of health and disease (DOHaD)« less

Plasma selenium levels and nonalcoholic fatty liver disease in Chinese adults: a cross-sectional analysis

PubMed Central

Yang, Zhen; Yan, Chonghuai; Liu, Gang; Niu, Yixin; Zhang, Weiwei; Lu, Shuai; Li, Xiaoyong; Zhang, Hongmei; Ning, Guang; Fan, Jiangao; Qin, Li; Su, Qing

2016-01-01

Selenium exposure can induce liver insulin resistance and increased liver triglyceride concentrations in animals, which may link to an increased risk of nonalcoholic fatty liver disease (NAFLD). However, epidemiological studies investigating the association between elevated plasma selenium levels and NAFLD were not available. We aimed to investigate the association of selenium levels with the prevalence of NAFLD in Chinese adults. This was a cross-sectional study of 8550 Chinese adults aged 40 yr or older in Shanghai, China. A questionnaire, anthropometric measurements, and laboratory tests were conducted. NAFLD was diagnosed by hepatic ultrasound after the exclusion of alcohol abuse and other liver diseases. Plasma selenium concentration was assessed by inductively coupled plasma mass spectroscopy. The median concentration of plasma selenium was 213.0 μg/L. Elevated plasma selenium levels were associated with higher triglycerides, LDL-cholesterol, fasting plasma glucose, post-loading plasma glucose, A1c, HOMA-IR, as well as ALT, AST and γ-GT (all P < 0.05). The odds ratios were substantially higher for NAFLD (OR = 1.54, 95% CI 1.13–2.18) in the highest selenium quartile compared with those in the lowest quartile, after adjustment for potential cofounder. The results of this study provided epidemiological evidence that increased plasma selenium level is associated with elevated prevalence of NAFLD. PMID:27853246

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

Determinants of maternal triglycerides in women with gestational diabetes mellitus in the Metformin in Gestational Diabetes (MiG) study.

PubMed

Barrett, Helen L; Dekker Nitert, Marloes; Jones, Lee; O'Rourke, Peter; Lust, Karin; Gatford, Kathryn L; De Blasio, Miles J; Coat, Suzette; Owens, Julie A; Hague, William M; McIntyre, H David; Callaway, Leonie; Rowan, Janet

2013-07-01

Factors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age, obesity, preeclampsia, and altered glucose metabolism. In a subgroup of women in the Metformin in Gestational Diabetes (MiG) trial, maternal plasma triglycerides increased more between enrollment (30 weeks) and 36 weeks in those treated with metformin compared with insulin. The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women. Of the 733 women randomized to metformin or insulin in the MiG trial, 432 (219 metformin and 213 insulin) had fasting plasma triglycerides measured at enrollment and at 36 weeks. Factors associated with maternal triglycerides were assessed using general linear modeling. Mean plasma triglyceride concentrations were 2.43 (95% CI 2.35-2.51) mmol/L at enrollment. Triglycerides were higher at 36 weeks in women randomized to metformin (2.94 [2.80-3.08] mmol/L; +23.13% [18.72-27.53%]) than insulin (2.65 [2.54-2.77] mmol/L, P = 0.002; +14.36% [10.91-17.82%], P = 0.002). At 36 weeks, triglycerides were associated with HbA1c (P = 0.03), ethnicity (P = 0.001), and treatment allocation (P = 0.005). In insulin-treated women, 36-week triglycerides were associated with 36-week HbA1c (P = 0.02), and in metformin-treated women, they were related to ethnicity. At 36 weeks, maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin. Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study.

Determinants of Maternal Triglycerides in Women With Gestational Diabetes Mellitus in the Metformin in Gestational Diabetes (MiG) Study

PubMed Central

Barrett, Helen L.; Dekker Nitert, Marloes; Jones, Lee; O’Rourke, Peter; Lust, Karin; Gatford, Kathryn L.; De Blasio, Miles J.; Coat, Suzette; Owens, Julie A.; Hague, William M.; McIntyre, H. David; Callaway, Leonie; Rowan, Janet

2013-01-01

OBJECTIVE Factors associated with increasing maternal triglyceride concentrations in late pregnancy include gestational age, obesity, preeclampsia, and altered glucose metabolism. In a subgroup of women in the Metformin in Gestational Diabetes (MiG) trial, maternal plasma triglycerides increased more between enrollment (30 weeks) and 36 weeks in those treated with metformin compared with insulin. The aim of this study was to explain this finding by examining factors potentially related to triglycerides in these women. RESEARCH DESIGN AND METHODS Of the 733 women randomized to metformin or insulin in the MiG trial, 432 (219 metformin and 213 insulin) had fasting plasma triglycerides measured at enrollment and at 36 weeks. Factors associated with maternal triglycerides were assessed using general linear modeling. RESULTS Mean plasma triglyceride concentrations were 2.43 (95% CI 2.35–2.51) mmol/L at enrollment. Triglycerides were higher at 36 weeks in women randomized to metformin (2.94 [2.80–3.08] mmol/L; +23.13% [18.72–27.53%]) than insulin (2.65 [2.54–2.77] mmol/L, P = 0.002; +14.36% [10.91–17.82%], P = 0.002). At 36 weeks, triglycerides were associated with HbA1c (P = 0.03), ethnicity (P = 0.001), and treatment allocation (P = 0.005). In insulin-treated women, 36-week triglycerides were associated with 36-week HbA1c (P = 0.02), and in metformin-treated women, they were related to ethnicity. CONCLUSIONS At 36 weeks, maternal triglycerides were related to glucose control in women treated with insulin and ethnicity in women treated with metformin. Whether there are ethnicity-related dietary changes or differences in metformin response that alter the relationship between glucose control and triglycerides requires further study. PMID:23393209

Microbial translocation in HIV infection is associated with dyslipidemia, insulin resistance, and risk of myocardial infarction.

PubMed

Pedersen, Karin K; Pedersen, Maria; Trøseid, Marius; Gaardbo, Julie C; Lund, Tamara T; Thomsen, Carsten; Gerstoft, Jan; Kvale, Dag; Nielsen, Susanne D

2013-12-15

Microbial translocation has been suggested to be a driver of immune activation and inflammation. It is hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals. Cross-sectional study of 60 HIV-infected patients on combination antiretroviral therapy with viral suppression >2 years and 31 healthy age-matched controls. Lipopolysaccharide (LPS) was analyzed by limulus amebocyte lysate colorimetric assay. Lipids, including cholesterol, low-density lipoprotein (LDL), and triglycerides, were measured. Glucose metabolism was determined using an oral glucose tolerance test. Body composition was determined using whole-body dual-energy x-ray absorptiometry scans and magnetic resonance imaging. The Framingham risk score was used to assess risk of cardiovascular disease and myocardial infarction. HIV-infected patients had higher level of LPS compared with controls (64 pg/mL vs. 50 pg/mL, P = 0.002). Likewise, HIV-infected patients had higher triglycerides, LDL, and fasting insulin as well as evidence of lower insulin sensitivity compared with controls. Among HIV-infected patients, high LPS was associated with a higher level of triglycerides and LDL and with lower insulin sensitivity. Importantly, among HIV-infected patients, high LPS was associated with a higher Framingham risk score. HIV-infected patients with suppressed viral replication had increased level of microbial translocation as measured by LPS. LPS was associated with cardiometabolic risk factors and increased Framingham risk score. Hence, the gastrointestinal mucosal barrier may be a potential therapeutic target to prevent dyslipidemia and future cardiovascular complications in HIV infection.

Intermittent cold exposure enhances fat accumulation in mice.

PubMed

Yoo, Hyung Sun; Qiao, Liping; Bosco, Chris; Leong, Lok-Hei; Lytle, Nikki; Feng, Gen-Sheng; Chi, Nai-Wen; Shao, Jianhua

2014-01-01

Due to its high energy consuming characteristics, brown adipose tissue (BAT) has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE), unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis.

Intermittent Cold Exposure Enhances Fat Accumulation in Mice

PubMed Central

Yoo, Hyung sun; Qiao, Liping; Bosco, Chris; Leong, Lok-Hei; Lytle, Nikki; Feng, Gen-Sheng; Chi, Nai-Wen; Shao, Jianhua

2014-01-01

Due to its high energy consuming characteristics, brown adipose tissue (BAT) has been suggested as a key player in energy metabolism. Cold exposure is a physiological activator of BAT. Intermittent cold exposure (ICE), unlike persistent exposure, is clinically feasible. The main objective of this study was to investigate whether ICE reduces adiposity in C57BL/6 mice. Surprisingly, we found that ICE actually increased adiposity despite enhancing Ucp1 expression in BAT and inducing beige adipocytes in subcutaneous white adipose tissue. ICE did not alter basal systemic insulin sensitivity, but it increased liver triglyceride content and secretion rate as well as blood triglyceride levels. Gene profiling further demonstrated that ICE, despite suppressing lipogenic gene expression in white adipose tissue and liver during cold exposure, enhanced lipogenesis between the exposure periods. Together, our results indicate that despite enhancing BAT recruitment, ICE in mice increases fat accumulation by stimulating de novo lipogenesis. PMID:24789228

Medium Chain Triglycerides enhances exercise endurance through the increased mitochondrial biogenesis and metabolism

PubMed Central

Han, Yi; Xu, Jiping; Li, Zhaoshen

2018-01-01

Medium Chain Triglycerides (MCT) is a dietary supplement and usually used along with medications for treating food absorption disorders including diarrhea, steatorrhea and liver disease. It has been shown that MCT plays a role in lowering weight, and decreasing metabolic syndrome, abdominal obesity and inflammation. However, it is still unknown whether MCT enhances exercise endurance. Here, we demonstrated that MCT containing diet improves high temperature induced exercise performance impairment. We found that MCT up-regulates the expression and protein levels of genes involved in mitochondrial biogenesis and metabolism. Further investigation demonstrated that the increased mitochondrial biogenesis and metabolism is mediated through the activation of Akt and AMPK signaling pathways and inhibition of TGF-β signaling pathway. Collectively, our findings indicate a beneficial effect of dietary MCT in exercise performance through the increase of mitochondrial biogenesis and metabolism. PMID:29420554

Dyslipidemia links obesity to early cerebral neurochemical alterations.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Tanaka, Hirofumi

2013-10-01

To examine the role of hypertension, hyperglycemia, and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Sixty-four adults, ages 40-60 years, underwent a health screen and proton magnetic resonance spectroscopy ((1) H MRS) of occipitoparietal gray matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI), and glutamate (Glu) relative to creatine (Cr). The causal steps approach and nonparametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride, and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing toward a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. Copyright © 2013 The Obesity Society.

Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal.

PubMed

Parra, Esteban J; Mazurek, Andrew; Gignoux, Christopher R; Sockell, Alexandra; Agostino, Michael; Morris, Andrew P; Petty, Lauren E; Hanis, Craig L; Cox, Nancy J; Valladares-Salgado, Adan; Below, Jennifer E; Cruz, Miguel

2017-01-01

We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30-40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene.

Simultaneous conversion of free fatty acids and triglycerides to biodiesel by immobilized Aspergillus oryzae expressing Fusarium heterosporum lipase.

PubMed

Amoah, Jerome; Quayson, Emmanuel; Hama, Shinji; Yoshida, Ayumi; Hasunuma, Tomohisa; Ogino, Chiaki; Kondo, Akihiko

2017-03-01

The presence of high levels of free fatty acids (FFA) in oil is a barrier to one-step biodiesel production. Undesirable soaps are formed during conventional chemical methods, and enzyme deactivation occurs when enzymatic methods are used. This work investigates an efficient technique to simultaneously convert a mixture of free fatty acids and triglycerides (TAG). A partial soybean hydrolysate containing 73.04% free fatty acids and 24.81% triglycerides was used as a substrate for the enzymatic production of fatty acid methyl ester (FAME). Whole-cell Candida antarctica lipase B-expressing Aspergillus oryzae, and Novozym 435 produced only 75.2 and 73.5% FAME, respectively. Fusarium heterosporum lipase-expressing A. oryzae produced more than 93% FAME in 72 h using three molar equivalents of methanol. FFA and TAG were converted simultaneously in the presence of increasing water content that resulted from esterification. Therefore, F. heterosporum lipase with a noted high level of tolerance of water could be useful in the industrial production of biodiesel from feedstock that has high proportion of free fatty acids. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Admixture mapping in two Mexican samples identifies significant associations of locus ancestry with triglyceride levels in the BUD13/ZNF259/APOA5 region and fine mapping points to rs964184 as the main driver of the association signal

PubMed Central

Mazurek, Andrew; Sockell, Alexandra; Morris, Andrew P.; Petty, Lauren E.; Hanis, Craig L.; Cox, Nancy J.; Cruz, Miguel

2017-01-01

We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30–40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene. PMID:28245265

Niemann-Pick C1 modulates hepatic triglyceride metabolism and its genetic variation contributes to serum triglyceride levels.

PubMed

Uronen, Riikka-Liisa; Lundmark, Per; Orho-Melander, Marju; Jauhiainen, Matti; Larsson, Kristina; Siegbahn, Agneta; Wallentin, Lars; Zethelius, Björn; Melander, Olle; Syvänen, Ann-Christine; Ikonen, Elina

2010-08-01

To study how Niemann-Pick disease type C1 (NPC1) influences hepatic triacylglycerol (TG) metabolism and to determine whether this is reflected in circulating lipid levels. In Npc1(-/-) mice, the hepatic cholesterol content is increased but the TG content is decreased. We investigated lipid metabolism in Npc1(-/-) mouse hepatocytes and the association of NPC1 single-nucleotide polymorphisms with circulating TGs in humans. TGs were reduced in Npc1(-/-) mouse serum and hepatocytes. In Npc1(-/-) hepatocytes, the incorporation of [3H]oleic acid and [3H]acetate into TG was decreased, but shunting of oleic acid- or acetate-derived [3H]carbons into cholesterol was increased. Inhibition of cholesterol synthesis normalized TG synthesis, content, and secretion in Npc1(-/-) hepatocytes, suggesting increased hepatic cholesterol neogenesis as a cause for the reduced TG content and secretion. We found a significant association between serum TG levels and 5 common NPC1 single-nucleotide polymorphisms in a cohort of 1053 men, with the lowest P=8.7 x 10(-4) for the single-nucleotide polymorphism rs1429934. The association between the rs1429934 A allele and higher TG levels was replicated in 2 additional cohorts, which included 8041 individuals. This study provides evidence of the following: (1) in mice, loss of NPC1 function reduces hepatocyte TG content and secretion by increasing the metabolic flux of carbons into cholesterol synthesis; and (2) common variation in NPC1 contributes to serum TG levels in humans.

Familial combined hyperlipidemia is associated with alterations in the cholesterol synthesis pathway

USDA-ARS?s Scientific Manuscript database

Familial combined hyperlipidemia (FCH) is a common familial lipid disorder characterized by increases in plasma total cholesterol, triglyceride, and apolipoprotein B-100 levels. In light of prior metabolic and genetic research, our purpose was to ascertain whether FCH cases had significant abnormali...

Alpha-lipoic acid reduces body weight and regulates triglycerides in obese patients with diabetes mellitus.

PubMed

Okanović, Azra; Prnjavorac, Besim; Jusufović, Edin; Sejdinović, Rifat

2015-08-01

To determine an influence of alpha-lipoic acid to reduction of body weight and regulation of total cholesterol concentration, triglycerides and glucose serum levels in obese patients with diabetes mellitus type 2. A prospective study includes two groups of obese patients with diabetes mellitus and signs of peripheral polyneuropathia: examined group (30 patients; 15 females and 15 males), and control group (30 patients; 12 females and 18 males). All were treated with metformin (850-1700 mg/day). Examined patients were additionally treated with alpha-lipoic acid 600 mg/day during 20 weeks. Body mass index and concentrations of total cholesterol, triglycerides and glucose in serum were compared before and after the treatment. The group treated with 600 mg alpha-lipoic acid lost significantly more weight, and had lower triglyceride level than the control group. There were no significant differences in total cholesterol and glucose serum levels between the groups. Alpha-lipoic acid of 600 mg/day treatment have influenced weight and triglycerides loss in obese patients with diabetes mellitus type 2. It should be considered as an important additive therapy in obese patients with diabetes mellitus type 2. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

Total saponins from Rosa laevigata Michx fruit attenuates hepatic steatosis induced by high-fat diet in rats.

PubMed

Dong, Deshi; Qi, Yan; Xu, Lina; Yin, Lianhong; Xu, Youwei; Han, Xu; Zhao, Yanyan; Peng, Jinyong

2014-12-01

The protective effects of total saponins from Rosa laevigata Michx fruit (RLTS) in high-fat diet (HFD)-induced rats were investigated. The results showed that oral administration of RLTS attenuated hepatic steatosis, significantly reduced the levels of body weight, alanine transaminase, aspartate transaminase, total cholesterol, total triglyceride, free fatty acids, low density lipoprotein, blood glucose, insulin and malondialdehyde, and increased high density lipoprotein and glutathione levels compared with the model group. Further investigations showed that RLTS affected fatty acid synthesis, fatty acid β-oxidation, fatty acid ω-oxidation, total cholesterol and triglyceride metabolism and synthesis. Moreover, the extract obviously suppressed HFD-induced oxidative stress and inflammation. These results suggest that RLTS should be developed to be one functional food or health product against non-alcoholic fatty liver disease (NAFLD) in the future.

Dual probiotic strains suppress high fructose-induced metabolic syndrome

PubMed Central

Park, Do-Young; Ahn, Young-Tae; Huh, Chul-Sung; McGregor, Robin A; Choi, Myung-Sook

2013-01-01

AIM: To investigate the effect of novel probiotics on the clinical characteristics of high-fructose induced metabolic syndrome. METHODS: Male Wistar rats aged 4 wk were fed a 70% w/w high-fructose diet (n = 27) or chow diet (n = 9) for 3 wk to induce metabolic syndrome, the rats were then randomized into groups and administered probiotic [Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032] at 109 cfu/d or 1010 cfu/d or placebo by oral gavage for 3 wk. Food intake and body weight were measured once a week. After 6 wk, the rats were fasted for 12 h, then anesthetized with diethyl ether and sacrificed. Blood samples were taken from the inferior vena cava for plasma analysis of glucose, insulin, C-peptide, total-cholesterol, triglycerides and thiobarbituric acid-reacting substances. Real-time polymerase chain reaction was performed using mouse-specific Taqman probe sets to assess genes related to fatty acid β-oxidation, lipogenesis and cholesterol metabolism in the liver. Target gene expression was normalized to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. RESULTS: Rodents fed a high-fructose diet developed clinical characteristics of the metabolic syndrome including increased plasma glucose, insulin, triglycerides, total cholesterol and oxidative stress levels, as well as increased liver mass and liver lipids compared to chow fed controls. Probiotic treatment (L. curvatus HY7601 and L. plantarum KY1032) at high (1010 cfu/d) or low dosage (109 cfu/d) lowered plasma glucose, insulin, triglycerides and oxidative stress levels. Only high-dose probiotic treatment reduced liver mass and liver cholesterol. Probiotic treatment reduced lipogenesis via down-regulation of SREBP1, FAS and SCD1 mRNA levels and increased β-oxidation via up-regulation of PPARα and CPT2 mRNA levels. CONCLUSION: Probiotic L. curvatus HY7601 and L. plantarum KY1032 combined suppressed the clinical characteristics of high-fructose-induced metabolic syndrome, therefore, may provide a natural alternative for the treatment of diet-induced metabolic syndrome. PMID:23345951

Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes.

PubMed

Calanna, S; Scicali, R; Di Pino, A; Knop, F K; Piro, S; Rabuazzo, A M; Purrello, F

2014-06-01

We aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. Ninety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39-46 mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48 mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39 mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT. Subjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Longitudinal analysis of haplotypes and polymorphisms of the APOA5 and APOC3 genes associated with variation in serum triglyceride levels: the Bogalusa Heart Study.

PubMed

Hallman, D Michael; Srinivasan, Sathanur R; Chen, Wei; Boerwinkle, Eric; Berenson, Gerald S

2006-12-01

Polymorphisms in the APOC3 and APOA5 genes, from the APOA1/APOC3/APOA4/APOA5 gene cluster on chromosome 11q23, have been associated with interindividual variation in plasma triglycerides. APOA5 polymorphisms implicated include 2 in the promoter region (-1131 T/C and -3 A/G) and 1 in exon 2 (+56 C/G). APOC3 polymorphisms implicated include 1 (SstI) in the 3' untranslated region and 1 (-2854 G/T) in the APOC3-APOA4 intergenic region. We analyzed the associations of haplotypes and multilocus genotypes of these polymorphisms on longitudinal serum triglyceride profiles in 360 African American and 823 white subjects from the Bogalusa Heart Study. Subjects were examined from 2 to 8 times (mean +/- SD, 5.4 +/- 1.3) between 1973 and 1996, at ages ranging from 4 to 38 years, with 1978 observations in African Americans and 4465 in whites. Serum triglycerides were significantly higher among whites across all ages. Allele frequencies differed significantly between African Americans and whites at all but the APOA5 +56 C/G locus. Linkage disequilibrium among the loci was higher in whites and haplotype diversity lower: 6 haplotypes had estimated frequencies of more than 1% in African Americans, 5 in whites. Individually, all polymorphisms except APOC3 -2854 G/T showed significant associations with triglyceride levels in the full sample. However, genotype models including all 5 loci showed significant triglyceride associations for only 3 (APOC3 SstI, APOA5 -1131 T/C, and APOA5 +56 C/G); significant interactions among them indicated their effects were not independent. Neither APOC3 -2854 G/T nor APOA5 -3 A/G had significant effects when the other 3 loci were in the models. The EM algorithm was used to estimate haplotype frequencies and assign haplotype probabilities to individuals, which is conditional on their genotypes; individuals' haplotype probability vectors were then used as predictors in multilevel mixed models of longitudinal triglyceride profiles. Of haplotypes comprising, in order, APOC3 SstI and -2854 G/T and APOA5 -1131 T/C, -3 A/G, and +56 C/G, 3 were significantly associated with higher triglycerides, even after adjusting for multiple tests: GGTAG (P = .002), GTTAG (P < .0001), and CGCGC (P = .0002). Each GGTAG haplotype carried would be expected to raise triglyceride levels (relative to those of GTTAC homozygotes) by approximately 19 mg/dL, each GTTAG haplotype by approximately 15 mg/dL, and each CGCGC haplotype by approximately 7 mg/dL. Haplotypes comprising the 3 loci implicated by genotype analyses (SstI, -1131 T/C, and +56 C/G) were also tested: haplotypes C_C_C and G_T_G significantly raised triglycerides, even after adjustment for multiple comparisons (P < .002 for both), with each copy of C_C_C expected to raise triglycerides by approximately 7 mg/dL and each copy of G_T_G by approximately 15 mg/dL. Overall, our findings support those of others in associating specific polymorphisms and haplotypes in the APOA1/C3/A4/A5 gene cluster with higher serum triglyceride levels. However, the degree to which polymorphisms in the APOC3 and APOA5 genes may be independently associated with triglyceride levels remains to be determined.

Long-Term Effects of Docosahexaenoic Acid-Bound Phospholipids and the Combination of Docosahexaenoic Acid-Bound Triglyceride and Egg Yolk Phospholipid on Lipid Metabolism in Mice

NASA Astrophysics Data System (ADS)

Che, Hongxia; Cui, Jie; Wen, Min; Xu, Jie; Yanagita, Teruyoshi; Wang, Qi; Xue, Changhu; Wang, Yuming

2018-04-01

The bioavailability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) depends on their chemical forms. This study investigated the long-term effects of DHA-bound triglyceride (TG-DHA), DHA-bound phospholipid (PL-DHA), and the combination of TG-DHA and egg yolk phospholipid (Egg-PL) on lipid metabolism in mice fed with a high-fat diet (fat levels of 22.5%). Male C57BL/6J mice were fed with different formulations containing 0.5% DHA, including TG-DHA, PL-DHA, and the combination of TG-DHA and Egg-PL, for 6 weeks. Serum, hepatic, and cerebral lipid concentrations and the fatty acid compositions of the liver and brain were determined. The concentrations of serum total triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and hepatic TG in the PL-DHA group and the combination group were significantly lower than those in the high-fat (HF) group ( P < 0.05). Atherogenic index (AI) of the PL-DHA group was significantly lower than that of the combination group ( P < 0.05). Hepatic TC level in the combination group was significantly lower than that in the HF group ( P < 0.05), but no significant difference was observed between the combination group and the PL-DHA group. Both the PL-DHA and the combination groups showed significantly increased DHA levels in the liver compared with the HF group ( P < 0.05). However, there were no obvious increases in the cerebral DHA levels in all DHA diet groups. These results suggest that PL-DHA was superior to the combination of TG-DHA and Egg-PL in decreasing the AI. Long-term dietary supplementation with low amount of DHA (0.5%) may improve hepatic DHA levels, although cerebral DHA levels may not be enhanced.

Leucine supplementation via drinking water reduces atherosclerotic lesions in apoE null mice

PubMed Central

Zhao, Yang; Dai, Xiao-yan; Zhou, Zhou; Zhao, Ge-xin; Wang, Xian; Xu, Ming-jiang

2016-01-01

Aim: Recent evidence suggests that the essential amino acid leucine may be involved in systemic cholesterol metabolism. In this study, we investigated the effects of leucine supplementation on the development of atherosclerosis in apoE null mice. Methods: ApoE null mice were fed with chow supplemented with leucine (1.5% w/v) in drinking water for 8 week. Aortic atherosclerotic lesions were examined using Oil Red O staining. Plasma lipoprotein-cholesterol levels were measured with fast protein liquid chromatography. Hepatic gene expression was detected using real-time PCR and Western blot analyses. Results: Leucine supplementation resulted in 57.6% reduction of aortic atherosclerotic lesion area in apoE null mice, accompanied by 41.2% decrease of serum LDL-C levels and 40.2% increase of serum HDL-C levels. The body weight, food intake and blood glucose level were not affected by leucine supplementation. Furthermore, leucine supplementation increased the expression of Abcg5 and Abcg8 (that were involved in hepatic cholesterol efflux) by 1.28- and 0.86-fold, respectively, and significantly increased their protein levels. Leucine supplementation also increased the expression of Srebf1, Scd1 and Pgc1b (that were involved in hepatic triglyceride metabolism) by 3.73-, 1.35- and 1.71-fold, respectively. Consequently, leucine supplementation resulted in 51.77% reduction of liver cholesterol content and 2.2-fold increase of liver triglyceride content. Additionally, leucine supplementation did not affect the serum levels of IL-6, IFN-γ, TNF-α, IL-10 and IL-12, but markedly decreased the serum level of MCP-1. Conclusion: Leucine supplementation effectively attenuates atherosclerosis in apoE null mice by improving the plasma lipid profile and reducing systemic inflammation. PMID:26687933

Toxicity of atrazine, glyphosate, and quinclorac in bullfrog tadpoles exposed to concentrations below legal limits.

PubMed

Dornelles, M F; Oliveira, G T

2016-01-01

This work sought to ascertain survival and possible changes in levels of glycogen, triglycerides, total lipids, cholesterol, protein, and lipid peroxidation in gills, liver, and muscle of bullfrog tadpoles (Lithobates catesbeianus) exposed to low concentrations of atrazine (2.5 μg L(-1)), glyphosate (18 μg L(-1)), and quinclorac (0.025 μg L(-1)) at laboratorial conditions. Tadpoles showed a reduction of glycogen and triglyceride in all organs and an increase in lipid peroxidation (LPO) compared with control animals. Total lipid in gills and muscle increased in exposure to atrazine, and gills alone in exposure to glyphosate, but decreased in gills, liver, and muscle after quinclorac. Cholesterol increased in gills and liver after atrazine, in gills and muscle after glyphosate, and decreased in liver after quinclorac. Total protein in gills decreased after exposure to all herbicides, increased in muscle after atrazine, and in liver and muscle after quinclorac. These findings show that at concentrations of these herbicides tested can lead to an increase in energy expenditure to maintain homeostasis and survival of these animals despite the increase in lipid peroxidation levels in all organs analyzed. Responses observed can be one of the factors responsible for the decline in the number of amphibians around the world.

Serum Chemerin Levels Are Associated with Abdominal Visceral Fat in Type 2 Diabetes.

PubMed

Han, Juyoung; Kim, So Hun; Suh, Young Ju; Lim, Hyun Ae; Shin, Heekyoung; Cho, Soon Gu; Kim, Chei Won; Lee, Seung Youn; Lee, Dae Hyung; Hong, Seongbin; Kim, Yong Seong; Nam, Moon-Suk

2016-06-01

Chemerin is a recently identified adipokine suggested to play a role in obesity and its metabolic complications. The relationship between visceral obesity and serum chemerin levels in type 2 diabetes (T2DM) is unknown and may differ from that of subjects without diabetes. Therefore, we evaluated whether serum chemerin was associated with visceral abdominal obesity in patients with T2DM. A total of 218 Korean patients with T2DM were enrolled and metabolic parameters, abdominal visceral and subcutaneous fat areas, and serum chemerin levels were measured. Serum chemerin level showed positive correlation with fasting insulin, HOMA-IR, serum triglyceride, serum creatinine, urine albumin/creatinine ratio, high-sensitivity C-reactive protein (hsCRP), fibrinogen, abdominal visceral fat area, visceral to subcutaneous fat area ratio, and negatively correlation with high density lipoprotein cholesterol and creatinine clearance (CCr) after adjusting for age, gender and body mass index. Multiple linear stepwise regression analysis showed that abdominal visceral fat area (β = 0.001, P < 0.001), serum triglyceride (β = 0.001, P < 0.001), CCr (β = -0.003, P = 0.001), hsCRP (β = 0.157, P = 0.001), fibrinogen (β = 0.001, P < 0.001) and BMI (β = 0.02, P = 0.008) independently affected log transformed serum chemerin levels. Higher serum chemerin level was associated with higher level of abdominal visceral fat area, serum triglyceride, hsCRP and fibrinogen and lower level of CCr in patients with T2DM. Serum chemerin may be used as a biomarker of visceral adiposity and chemerin may play a role in inflammation, decreased renal function, and increased cardiovascular risk in T2DM.

Systematic evaluation of environmental factors: persistent pollutants and nutrients correlated with serum lipid levels

PubMed Central

Patel, Chirag J; Cullen, Mark R; Ioannidis, John PA; Butte, Atul J

2012-01-01

Background Both genetic and environmental factors contribute to triglyceride, low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) levels. Although genome-wide association studies are currently testing the genetic factors systematically, testing and reporting one or a few factors at a time can lead to fragmented literature for environmental chemical factors. We screened for correlation between environmental factors and lipid levels, utilizing four independent surveys with information on 188 environmental factors from the Centers of Disease Control, National Health and Nutrition Examination Survey, collected between 1999 and 2006. Methods We used linear regression to correlate each environmental chemical factor to triglycerides, LDL-C and HDL-C adjusting for age, age2, sex, ethnicity, socio-economic status and body mass index. Final estimates were adjusted for waist circumference, diabetes status, blood pressure and survey. Multiple comparisons were controlled for by estimating the false discovery rate and significant findings were tentatively validated in an independent survey. Results We identified and validated 29, 9 and 17 environmental factors correlated with triglycerides, LDL-C and HDL-C levels, respectively. Findings include hydrocarbons and nicotine associated with lower HDL-C and vitamin E (γ-tocopherol) associated with unfavourable lipid levels. Higher triglycerides and lower HDL-C were correlated with higher levels of fat-soluble contaminants (e.g. polychlorinated biphenyls and dibenzofurans). Nutrients and vitamin markers (e.g. vitamins B, D and carotenes), were associated with favourable triglyceride and HDL-C levels. Conclusions Our systematic association study has enabled us to postulate about broad environmental correlation to lipid levels. Although subject to confounding and reverse causality bias, these findings merit evaluation in additional cohorts. PMID:22421054

Polyunsaturated fatty acids effect on serum triglycerides concentration in presence of metabolic syndrome components. The Alaska-Siberia Project

PubMed Central

Lopez-Alvarenga, Juan C.; Ebbesson, Sven O E; Ebbesson, Lars O E; Tejero, M Elizabeth; Voruganti, V. Saroja; Comuzzie, Anthony G

2009-01-01

Serum fatty acids (FA) have wide effects on metabolism: Serum saturated fatty acids (SFA) increase triglyceride (TG) levels in plasma while polyunsaturated fatty acids (PUFA) reduce them. Traditionally, Eskimos have a high consumption of omega -3 fatty acids (ω–3 FA), but the westernization of their food habits have increased their dietary SFAs, partly reflected in their serum concentrations. We studied the joint effect of serum SFAs and PUFAs on circulating levels of TG in the presence of metabolic syndrome components. We included 212 men and 240 women (age 47.9±15.7 y, BMI 26.9±5.3) from four villages located in Alaska for a cross sectional study. Generalized linear models were employed to build surface responses of TG as in functions of SFAs and PUFAs measured in blood samples adjusting by sex, BMI and village. The effects of individual FAs were assessed by multiple linear regression analysis and partial correlations (r) were calculated. The most important predictors for TG levels were glucose tolerance (r = 0.116, p = 0.018) and BMI (r = 0.42, p<0.001). TG concentration showed negative associations with 20:3ω-6 (r =− 0.16, p = 0.001), 20:4ω-6 (r = −0.14, p=0.005), 20:5ω-3 (r = −0.17, p<0.001) and 22:5ω-3 (r = −0.26, p<0.001), and positive associations with palmitic acid (r = 0.16, p<0.001) and 18:3ω-3 (r = 0.15, p<0.001). The surface response analysis suggested that the effect of palmitic acid on TG is blunted in different degrees according to the PUFA chemical structure. The long chain ω-3, even in presence of high levels of SF, was associated with lower triglyceride levels. Eicosapentanoic acid (20:5ω3) had the strongest effect against palmitic acid on TG. The total FA showed moderate association with levels of TG, while SFA was positively associated, and large chain PUFA negatively. The westernized dietary habits among Eskimos are likely to change their metabolic profile and increase comorbidities related to metabolic disease. PMID:19766268

Increased Pre- and Post-Meal Free Fatty Acid Levels in Black, Obese Adolescents

PubMed Central

Rauch, Lindsey; Huang, Hong; Bauer, John A.; Hoffman, Robert P.

2016-01-01

Abstract Background: Black adolescents are at increased risk of cardiometabolic disease but have lower fasting triglyceride, which is usually associated with decreased risk. No one has studied racial differences in triglycerides or free fatty acids (FFAs) after a high-fat meal. Methods: Oral glucose tolerance testing was used to assess insulin secretion, sensitivity, and disposition index (DI). Endothelial function, triglycerides, FFA, c-reactive protein, interleukin 6 (IL6), and adiponectin were measured both pre- and 3 hr postprandially (McDonald's Big Breakfast® and 12 ounce Sprite®) in obese adolescents (10–13 years, 9 black and 7 white). Endothelial function was assessed using reactive hyperemic changes in forearm vascular resistance (FVR). Results: Oral glucose tolerance test (OGTT) showed no difference in insulin sensitivity, but blacks tended to have (P = 0.08) higher insulin secretion and had increased DI (P = 0.003). After a high-fat meal, triglycerides increased in both groups (P < 0.001), tended to be lower in blacks compared with whites preprandially (64 ± 33 mg/dL vs 110 ± 80, P = 0.064), and was lower postprandially (112 ± 63 vs 188 ± 112, P = 0.039). Pre- and postprandial FFA (Black: 0.58 ± 0.15 and 0.39 ± 0.18 vs. white: 0.44 ± 0.14 and 0.26 ± 0.06, P = 0.020) and adiponectin (P = 0.002) were increased in blacks. FFA decreased in both groups postprandially (P = 0.002). IL6 increased after the meal (P = 0.022). Endothelial function decreased postprandially (P < 0.02), but this was due to a decrease in preocclusion FVR. Conclusions: These results indicate that differences in fat metabolism are present in both black and white obese adolescents. How these differences explain higher rates of cardiometabolic disease in blacks is unclear. PMID:27419255

Maternal serum markers of lipid metabolism in relation to neonatal anthropometry

PubMed Central

Boghossian, Nansi S.; Mendola, Pauline; Liu, Aiyi; Robledo, Candace; Yeung, Edwina H.

2017-01-01

Objective To examine associations between lipids (HDL, LDL, total cholesterol, triglycerides, lipoprotein (a)) measured on average three time-points during pregnancy and neonatal anthropometrics. Study Design Stored samples from a preeclampsia trial measured as part of a case-control study from five US centers (1992-1995) were used. The sample included women without pregnancy complications (n=136), and cases of gestational diabetes (n=93), abnormal glucose tolerance (n=76), gestational hypertension (n=170), and preeclampsia (n=177). Linear regression and linear mixed-effects models estimated adjusted associations between lipids and birth weight z-score, ponderal index, length, and head circumference. Results Among women without complications, cross-sectional associations between total cholesterol measured at different gestational ages increased ponderal index 2.23 to 2.55 kg/m3 per-unit increase in cholesterol. HDL was inversely associated with birth length (β's=-2.21 and -2.56 cm). For gestational hypertension, triglycerides were associated with birth weight z-score (β's=0.24 to 0.31). For preeclampsia, HDL was associated with lower birth weight z-scores (β's=-0.49 and -0.82). Women with gestational diabetes or abnormal glucose tolerance had inconsistent associations. Examining the level changes across pregnancy, each 0.0037 mmol/L increase in HDL was associated with decreased birth weight z-score (β=-0.22), length (β=-0.24 cm), and head circumference (β=-0.24 cm) whereas each 0.028 mmol/L increase in triglycerides was associated with increased birth weight z-score (β=0.13) and head circumference (β=0.19 cm). Conclusion Although associations varied by complications, in general, growth promoting fuels as total cholesterol and triglycerides were associated with increased neonatal size whereas high HDL was associated with smaller size. Maternal HDL that failed to decrease over pregnancy was associated with smaller neonate size. PMID:28333159

Increased Pre- and Post-Meal Free Fatty Acid Levels in Black, Obese Adolescents.

PubMed

Cazeau, Rachel-Marie; Rauch, Lindsey; Huang, Hong; Bauer, John A; Hoffman, Robert P

2016-09-01

Black adolescents are at increased risk of cardiometabolic disease but have lower fasting triglyceride, which is usually associated with decreased risk. No one has studied racial differences in triglycerides or free fatty acids (FFAs) after a high-fat meal. Oral glucose tolerance testing was used to assess insulin secretion, sensitivity, and disposition index (DI). Endothelial function, triglycerides, FFA, c-reactive protein, interleukin 6 (IL6), and adiponectin were measured both pre- and 3 hr postprandially (McDonald's Big Breakfast(®) and 12 ounce Sprite(®)) in obese adolescents (10-13 years, 9 black and 7 white). Endothelial function was assessed using reactive hyperemic changes in forearm vascular resistance (FVR). Oral glucose tolerance test (OGTT) showed no difference in insulin sensitivity, but blacks tended to have (P = 0.08) higher insulin secretion and had increased DI (P = 0.003). After a high-fat meal, triglycerides increased in both groups (P < 0.001), tended to be lower in blacks compared with whites preprandially (64 ± 33 mg/dL vs 110 ± 80, P = 0.064), and was lower postprandially (112 ± 63 vs 188 ± 112, P = 0.039). Pre- and postprandial FFA (Black: 0.58 ± 0.15 and 0.39 ± 0.18 vs. white: 0.44 ± 0.14 and 0.26 ± 0.06, P = 0.020) and adiponectin (P = 0.002) were increased in blacks. FFA decreased in both groups postprandially (P = 0.002). IL6 increased after the meal (P = 0.022). Endothelial function decreased postprandially (P < 0.02), but this was due to a decrease in preocclusion FVR. These results indicate that differences in fat metabolism are present in both black and white obese adolescents. How these differences explain higher rates of cardiometabolic disease in blacks is unclear.

Role of Insulin in Endogenous Hypertriglyceridemia*

PubMed Central

Reaven, Gerald M.; Lerner, Roger L.; Stern, Michael P.; Farquhar, John W.

1967-01-01

Dietary carbohydrate accentuation of endogenous triglyceride production has been studied in 33 patients. A broad and relatively continuous spectrum of steady-state plasma triglyceride concentrations was produced in 31 of the 33 subjects during 3 wk of a high carbohydrate (fat-free) liquid formula diet. Two patients developed plasma triglyceride concentrations in excess of 2000 mg/100 ml, and these were the only patients we have studied in which carbohydrate induction of hypertriglyceridemia seemed to be associated with a defect in endogenous plasma triglyceride removal mechanisms. In the remaining 31 patients the degree of hypertriglyceridemia was highly correlated with the insulin response elicited by the ingestion of the high carbohydrate formula (P < 0.005). No significant correlation existed between fasting plasma triglyceride concentration and either plasma glucose or free fatty acid concentrations after the high carbohydrate diet, nor was the degree of hypertriglyceridemia related to degree of obesity. It is suggested that hypertriglyceridemia in most subjects results from an increase in hepatic triglyceride secretion rate secondary to exaggerated postprandial increases in plasma insulin concentration. Images PMID:6061748

Association of gene variants with lipid levels in response to fenofibrate is influenced by metabolic syndrome status

USDA-ARS?s Scientific Manuscript database

Fenofibrate therapy reduces serum triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C) and thus addresses the atherogenic dyslipidemia associated with metabolic syndrome (MetS). Our hypothesis is that genetic factors contribute to the variability of lipid response to fenofib...

Pulicaria jaubertii extract prevents triglyceride deposition in 3T3-L1 adipocytes

USDA-ARS?s Scientific Manuscript database

Currently, levels of obesity in Middle Eastern countries are increasing. Phytochemicals have anti-obesogenic properties as evidenced by prevention of adipocyte differentiation. In Yemen, Pulicaria jaubertii E.Gamal-Eldin (PJ) is a food additive and a traditional medicine. We tested the ability of ex...

[Effects of smoking and alcohol consumptionon reproductive and metabolic indicators in young men in western siberia].

PubMed

Osadchuk, L V; Popova, A V; Erkovich, A A; Voroshilova, N A; Osadchuk, A V

2017-09-01

Smoking and alcohol consumption remain widespread throughout the world, including Russia. Recently, due to the increase in male infertility and subfertility, special attention has been paid to the effects of smoking and alcohol on the reproductive health of young men. The aim of this study was to assess the effects of smoking and moderate alcohol consumption on spermatogenesis, reproductive hormone levels and metabolic status in young men living in Western Siberia (Novosibirsk). One hundred thirty-three volunteers (mean age 21.1+/-0.3 years) were tested for the sperm concentration, the proportion of mobile and morphologically normal spermatozoa in the ejaculate, blood serum levels of follicle-stimulating and luteinizing hormones, prolactin, testosterone, estradiol, inhibin B, triglycerides, total cholesterol, high and low density lipoprotein cholesterol, glucose and uric acid. and conclusions The studied lifestyle factors were found to have no effects on spermatogenesis. Smoking more than 10 cigarettes per day and a moderate frequency of alcohol consumption (up to 1 time per week) was associated with higher blood serum testosterone levels and engaging in more frequent sexual contacts compared to non-smoking and non-drinking men. Drinking alcohol more than once a week and smoking more than 8 cigarettes per day was associated, along with the increase in testosterone levels and the frequency of sexual contacts, with lower levels of follicle-stimulating hormone and higher serum triglyceride levels. Thus, in young men, frequent drinking and smoking can alter the hormonal and metabolic balance, which, as the duration of the exposure and the strength of the factors increase, will increase the risk of reproductive disorders.

Waist circumference, body mass index, serum uric acid, blood sugar, and triglyceride levels are important risk factors for abnormal liver function tests in the Taiwanese population.

PubMed

Hsieh, Meng-Hsuan; Lin, Wen-Yi; Chien, Hsu-Han; Chien, Li-Ho; Huang, Chao-Kuan; Yang, Jeng-Fu; Chang, Ning-Chia; Huang, Chung-Feng; Wang, Chao-Ling; Chuang, Wan-Long; Yu, Ming-Lung; Dai, Chia-Yen; Ho, Chi-Kung

2012-09-01

Several studies have found that metabolic syndrome and uric acid level are related to abnormal liver function test results. The aim of this study was to explore the associations of risk factors [including blood pressure, blood sugar, total cholesterol, triglyceride, uric acid, waist circumference and body mass index (BMI) measurements] with abnormal liver function in the Taiwanese population.In total, 11,411 Taiwanese adults were enrolled in this study. Blood pressure was assessed according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, fasting blood sugar level according to the Bureau of Health Promotion, Department of Health, R.O.C., criteria, total cholesterol and triglyceride levels according to the Third Report of the National Cholesterol Education Program Adult Treatment Panel III criteria, BMI according to the Asia-Pacific criteria, and waist circumference according to the Revised Diagnostic Criteria of Metabolic Syndrome in Taiwan. The prevalence of a past history of hypertension and diabetes mellitus was 17.7% and 6.5%, respectively, and the rates of abnormal measurements of blood pressure, BMI, waist circumference, fasting blood sugar, triglyceride, total cholesterol, uric acid (male/female), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were 76.2%, 67.6%, 40.0%, 28.6%, 30.6%, 57.3%, 37.9%/21.9%, 14.6% and 21.3%, respectively. Multivariate analysis showed that waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels were related to abnormal AST and ALT (p<0.05), but the odds ratio for waist circumference was larger than that for BMI. In conclusion, waist circumference, BMI, serum uric acid, blood sugar, and triglyceride levels are important risk factors for abnormal AST and ALT readings in Taiwanese adults. Waist circumference might be a better indicator of risk of abnormal liver function than BMI. Copyright © 2012. Published by Elsevier B.V.

Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles.

PubMed Central

Aalto-Setälä, K; Fisher, E A; Chen, X; Chajek-Shaul, T; Hayek, T; Zechner, R; Walsh, A; Ramakrishnan, R; Ginsberg, H N; Breslow, J L

1992-01-01

Hypertriglyceridemia is common in the general population, but its mechanism is largely unknown. In previous work human apo CIII transgenic (HuCIIITg) mice were found to have elevated triglyceride levels. In this report, the mechanism for the hypertriglyceridemia was studied. Two different HuCIIITg mouse lines were used: a low expressor line with serum triglycerides of approximately 280 mg/dl, and a high expressor line with serum triglycerides of approximately 1,000 mg/dl. Elevated triglycerides were mainly in VLDL. VLDL particles were 1.5 times more triglyceride-rich in high expressor mice than in controls. The total amount of apo CIII (human and mouse) per VLDL particle was 2 and 2.5 times the normal amount in low and high expressors, respectively. Mouse apo E was decreased by 35 and 77% in low and high expressor mice, respectively. Under electron microscopy, VLDL particles from low and high expressor mice were found to have a larger mean diameter, 55.2 +/- 16.6 and 58.2 +/- 17.8 nm, respectively, compared with 51.0 +/- 13.4 nm from control mice. In in vivo studies, radiolabeled VLDL fractional catabolic rate (FCR) was reduced in low and high expressor mice to 2.58 and 0.77 pools/h, respectively, compared with 7.67 pools/h in controls, with no significant differences in the VLDL production rates. In an attempt to explain the reduced VLDL FCR in transgenic mice, tissue lipoprotein lipase (LPL) activity was determined in control and high expressor mice and no differences were observed. Also, VLDLs obtained from control and high expressor mice were found to be equally good substrates for purified LPL. Thus excess apo CIII in HuCIIITg mice does not cause reduced VLDL FCR by suppressing the amount of extractable LPL in tissues or making HuCIIITg VLDL a bad substrate for LPL. Tissue uptake of VLDL was studied in hepatoma cell cultures, and VLDL from transgenic mice was found to be taken up much more slowly than control VLDL (P < 0.0001), indicating that HuCIIITg VLDL is not well recognized by lipoprotein receptors. Additional in vivo studies with Triton-treated mice showed increased VLDL triglyceride, but not apo B, production in the HuCIIITg mice compared with controls. Tissue culture studies with primary hepatocytes showed a modest increase in triglyceride, but not apo B or total protein, secretion in high expressor mice compared with controls. In summary, hypertriglyceridemia in HuCIIITg mice appears to result primarily from decreased tissue uptake of triglyceride-rich particles from the circulation, which is most likely due to increased apo CIII and decreased apo E on VLDL particles. the HuCIIITg mouse appears to be a suitable animal model of primary familial hypertriglyceridemia, and these studies suggest a possible mechanism for this common lipoprotein disorder. Images PMID:1430212

Physical Activity and Sedentary Behavior in Adolescents With Type 1 Diabetes

PubMed Central

Michaliszyn, Sara Fleet; Faulkner, Melissa Spezia

2014-01-01

The purpose of this study was to describe the associations between levels of physical activity measured by accelerometry and changes in fitness, body composition, lipids, and glucose control (i.e., glycosolated hemoglobin [A1C]) in a sample of 16 adolescents with type 1 diabetes participating in a personalized exercise program. More sedentary activity was associated with lower fitness and fat free mass and increased total cholesterol, low-density lipoprotein (LDL-c), and triglycerides (p < .05). Greater amounts of moderate to vigorous activity were associated with higher fitness and fat free mass, and decreased total cholesterol, LDL-c, triglycerides, and A1C (p < .05). Findings support the beneficial effects of increased moderate activity and decreased sedentary behavior to reduce cardiovascular risks and improve glucose control in adolescents with type 1 diabetes. PMID:20672318

Preparation of a Homologous (Human) Intravenous Botulinal Immune Globulin.

DTIC Science & Technology

1983-05-01

lipoprotein ( HDL ) per ml of plasma to ŗ.06 mg/ml for beta- lipoprotein (LDL). Triglyceride and cholesterol levels were intermediate within this...OF LIPOPROTEIN DURING FRACTIONATION "( HDL ) (LDL) Triglyceride Cholesterol cxLipoprotein 8 LipoproteinSample mg/ml mg/ml mg/mi m/ml IVBG-l.A:"Plasma...plasminogen, prekallikrein, triglycerides , cholesterol , alpha- lipoprotein , beta- lipoprotein , clotting factors, fibrinogen and complement

Functional electrical stimulation cycling improves body composition, metabolic and neural factors in persons with spinal cord injury.

PubMed

Griffin, L; Decker, M J; Hwang, J Y; Wang, B; Kitchen, K; Ding, Z; Ivy, J L

2009-08-01

Persons with spinal cord injury (SCI) are at a heightened risk of developing type II diabetes and cardiovascular disease. The purpose of this investigation was to conduct an analysis of metabolic, body composition, and neurological factors before and after 10 weeks of functional electrical stimulation (FES) cycling in persons with SCI. Eighteen individuals with SCI received FES cycling 2-3 times per week for 10 weeks. Body composition was analyzed by dual X-ray absorptiometry. The American Spinal Injury Association (ASIA) neurological classification of SCI test battery was used to assess motor and sensory function. An oral glucose tolerance (OGTT) and insulin-response test was performed to assess blood glucose control. Additional metabolic variables including plasma cholesterol (total-C, HDL-C, LDL-C), triglyceride, and inflammatory markers (IL-6, TNF-alpha, and CRP) were also measured. Total FES cycling power and work done increased with training. Lean muscle mass also increased, whereas, bone and adipose mass did not change. The ASIA motor and sensory scores for the lower extremity significantly increased with training. Blood glucose and insulin levels were lower following the OGTT after 10 weeks of training. Triglyceride levels did not change following training. However, levels of IL-6, TNF-alpha, and CRP were all significantly reduced.

National Survey on Internal Quality Control Practice for Lipid Parameters in Laboratories of China from 2014 to 2016.

PubMed

Ye, Yuanyuan; Wang, Wei; Zhao, Haijian; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

2017-09-01

To investigate the situation of Internal Quality Control (IQC) practice for total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol from 2014 to 2016 in laboratories in China and provide improvement measurements. A web-based External Quality Assessment (EQA) system was used to collect IQC data of lipid parameters in laboratories which continuously participated in the national EQA programs in China from 2014 to 2016. Pass rate of the coefficients of variation (CVs) of two level quality controls in four lipid parameters were calculated according to six quality specifications for precision to evaluate the current status of precision level of the four lipid parameters and their change over time in China. 533, 512, 504, and 466 laboratories continuously reported the data of level one for total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol, and 212, 210, 208 and 198 laboratories reported the level two, respectively. The percentage of laboratories meeting the quality specification varied based on different criteria. Non-significant change can be found in the pass rate of CVs over time. The number of laboratories using a closed system increased over time, but still only accounted for a small proportion. There is no significant difference in the pass rate of CVs between closed and open systems. Triglycerides currently have a fairly good performance in China. While the performance of laboratories on total cholesterol, HDL-cholesterol and LDL-cholesterol has yet to be improved.

Interactions between fatty acid synthesis, oxidation, and esterification in the production of triglyceride-rich lipoproteins by the liver.

PubMed

Fukuda, N; Ontko, J A

1984-08-01

In a series of experiments with male rat livers perfused with or without 5-tetradecyloxy-2-furoic acid (TOFA) in the presence and absence of oleate, the relationships between fatty acid synthesis, oxidation, and esterification from newly synthesized and exogenous fatty acid substrates have been examined. When livers from fed rats were perfused without exogenous fatty acid substrate, 20% of the triglyceride secreted was derived from de novo fatty acid synthesis. Addition of TOFA caused immediate and nearly complete inhibition of fatty acid synthesis, measured by incorporation of 3H2O into fatty acids. Concurrently, ketone body production increased 140% and triglyceride secretion decreased 84%. These marked reciprocal alterations in fatty acid synthesis and oxidation in the liver almost completely abolished the production of very low density lipoproteins (VLDL). Cholesterol synthesis was also depressed by TOFA, suggesting that this drug also inhibited lipid synthesis at a site other than acetyl-CoA carboxylase. When livers from fed rats were supplied with a continuous infusion of [1-14C]oleate as exogenous substrate, similar proportions, about 45-47%, of both ketone bodies and triglyceride in the perfusate were derived from the infused [1-14C]oleate. The production of ketone bodies was markedly increased by TOFA; the secretion of triglyceride and cholesterol were decreased. Altered conversion of [1-14C]oleate into these products occurred in parallel. While TOFA decreased esterification of oleate into triglyceride, incorporation of [1-14C]oleate into liver phospholipid was increased, indicating that TOFA also affected glycerolipid synthesis at the stage of diglyceride processing. The decreased secretion of triglyceride and cholesterol following TOFA treatment was localized almost exclusively in VLDL. The specific activities of 3H and of 14C fatty acids in triglyceride of the perfusate were greater than those of liver triglyceride, indicating preferential secretion of triglyceride produced from both de novo fatty acid synthesis and from infused free fatty acid substrate. These observations suggest the following chain of events in the liver following TOFA treatment: inhibition of fatty acid and cholesterol synthesis; increased fatty acid oxidation and ketogenesis; decreased triglyceride synthesis as a result of inhibition of fatty acid synthesis, stimulation of fatty acid oxidation, and altered partition of diglyceride between triglyceride and phospholipid synthesis; and decreased production of VLDL. These comparative rat liver perfusion experiments indicate that free fatty acids provide the major source of substrate for the hepatic production of triglyceri

A comparison of medium-chain and long-chain triglycerides in surgical patients.

PubMed Central

Jiang, Z M; Zhang, S Y; Wang, X R; Yang, N F; Zhu, Y; Wilmore, D

1993-01-01

Available lipid emulsions made from soybean or safflower oil are classified as long-chain triglycerides (LCT). In contrast, medium-chain triglyceride (MCT) emulsions have different physical properties and are metabolized by other biochemical pathways. To compare the differences between these two fat emulsions, the authors studied 12 surgical patients and 6 volunteers. These subjects were randomly assigned to receive parenteral nutrition with MCT or LCT emulsion. Measurement of arterial and venous concentration differences across the forearm demonstrated that muscle utilization was significantly improved with MCT administration. There was also a trend toward improved nitrogen balance in the MCT group, and less weight loss in the postoperative period also was observed in this group. During the fat clearance test, the serum ketone concentrations were significantly higher in the MCT than the LCT group. The improvement in nitrogen retention may be associated with increasing ketone and insulin levels. Fat emulsions containing 50% MCT are safe for use in parenteral nutrition and may provide an alternate fuel that improves protein metabolism. PMID:8439215

Therapeutic effects of marshmallow (Althaea officinalis L.) extract on plasma biochemical parameters of common carp infected with Aeromonas hydrophila

PubMed Central

Banaee, Mahdi; Soleimany, Vahid; Nematdoost Haghi, Behzad

2017-01-01

This study evaluated preclinical and clinical safety of marshmallow (Althaea officinalis L.) extract as a naturopathic medicine in common carp deliberately infected with Aeromonas hydrophila. The fish were fed 0 (control), 2.50, 5.00 and 10.00 g of marshmallow extract for 60 days in a preclinical experiment and then, challenged with A. hydrophila for a 10-day experiment. Significant increases were observed in aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK) activities and plasma creatinine levels in fish fed 10 g marshmallow extract per kg feed. However, alanine aminotransferase (ALT) significantly decreased on day 60. The fish fed 2.50 g marshmallow extract per kg feed indicated increased levels of total protein and globulin. There were no significant changes in albumin levels (p > 0.05). 2.50 and 5.00 g marshmallow significantly decreased triglyceride and cholesterol levels and increased glucose levels (p < 0.05). A. hydrophila significantly increased AST, ALT, LDH, ALP and CPK activities and plasma glucose, cholesterol, triglycerides and creatinine levels after 10 days (p < 0.05). Total plasma protein, albumin and globulin levels in fish challenged with A. hydrophila were significantly lower than the control group (p < 0.05). Marshmallow extract at 5.00 and 10.00 g can adjust plasma biochemical parameters in fish challenged with A. hydrophila. The results of preclinical studies and pharmaceutical toxicity of marshmallow extract revealed that dietary levels lower than 5.00 g were safe and effective. The results of this clinical study demonstrated that marshmallow extract (5.00 g kg-1 feed) can protect fish against A. hydrophila. PMID:28785391

Therapeutic effects of marshmallow (Althaea officinalis L.) extract on plasma biochemical parameters of common carp infected with Aeromonas hydrophila.

PubMed

Banaee, Mahdi; Soleimany, Vahid; Nematdoost Haghi, Behzad

2017-01-01

This study evaluated preclinical and clinical safety of marshmallow ( Althaea officinalis L.) extract as a naturopathic medicine in common carp deliberately infected with Aeromonas hydrophila . The fish were fed 0 (control), 2.50, 5.00 and 10.00 g of marshmallow extract for 60 days in a preclinical experiment and then, challenged with A. hydrophila for a 10-day experiment. Significant increases were observed in aspartate aminotransferase (AST), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), creatine phosphokinase (CPK) activities and plasma creatinine levels in fish fed 10 g marshmallow extract per kg feed. However, alanine aminotransferase (ALT) significantly decreased on day 60. The fish fed 2.50 g marshmallow extract per kg feed indicated increased levels of total protein and globulin. There were no significant changes in albumin levels ( p > 0.05). 2.50 and 5.00 g marshmallow significantly decreased triglyceride and cholesterol levels and increased glucose levels ( p < 0.05). A. hydrophila significantly increased AST, ALT, LDH, ALP and CPK activities and plasma glucose, cholesterol, triglycerides and creatinine levels after 10 days ( p < 0.05). Total plasma protein, albumin and globulin levels in fish challenged with A. hydrophila were significantly lower than the control group ( p < 0.05). Marshmallow extract at 5.00 and 10.00 g can adjust plasma biochemical parameters in fish challenged with A. hydrophila . The results of preclinical studies and pharmaceutical toxicity of marshmallow extract revealed that dietary levels lower than 5.00 g were safe and effective. The results of this clinical study demonstrated that marshmallow extract (5.00 g kg -1 feed) can protect fish against A. hydrophila .

TM6SF2 Glu167Lys polymorphism is associated with low levels of LDL-cholesterol and increased liver injury in obese children.

PubMed

Grandone, A; Cozzolino, D; Marzuillo, P; Cirillo, G; Di Sessa, A; Ruggiero, L; Di Palma, M R; Perrone, L; Miraglia Del Giudice, E

2016-04-01

The Glu167Lys (E167K) transmembrane 6 superfamily member 2 (TM6SF2) variant has been associated with liver steatosis, high alanine transaminase (ALT) levels and reduced plasma levels of liver-derived triglyceride-rich lipoproteins. The objectives of this study were to investigate in a group of obese children the association among the 167K allele of TM6SF2 gene and ALT, cholesterol and triglycerides levels, and hepatic steatosis, and to evaluate the potential interaction between this variant and the I148M patatin like phospholipase 3 gene (PNPLA3) polymorphism on liver enzymes. We genotyped 1010 obese children for TM6SF2 E167K and PNPLA3 I148M polymorphisms. Anthropometrical and biochemical data were collected. Ultrasound imaging of the liver was performed. The 167K allele showed an association with steatosis (P < 0.0001), higher ALT levels (P < 0.001) and lower total cholesterol (P < 0.00001), low-density lipoprotein cholesterol (P < 0.0001), triglycerides (P = 0.02) and non-high-density lipoprotein cholesterol levels (P < 0.000001). The subjects homozygous for the PNPLA3 148M allele carrying the rare variant of TM6SF2 showed an odds ratio of 12.2 (confidence interval 3.8-39.6, P = 0.000001) to present hypertransaminasaemia compared with the remaining patients. Although the TMS6SF2 E167K variant predisposes the obese children to non-alcoholic fatty liver disease, there is an association between this variant and lower levels of cardiovascular risk factors. Overall, the data suggest differential effects of TMS6SF2 E167K variant on liver and heart health. © 2015 World Obesity.

Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling.

PubMed

Nolan, C J; Leahy, J L; Delghingaro-Augusto, V; Moibi, J; Soni, K; Peyot, M-L; Fortier, M; Guay, C; Lamontagne, J; Barbeau, A; Przybytkowski, E; Joly, E; Masiello, P; Wang, S; Mitchell, G A; Prentki, M

2006-09-01

The aim of this study was to determine the role of fatty acid signalling in islet beta cell compensation for insulin resistance in the Zucker fatty fa/fa (ZF) rat, a genetic model of severe obesity, hyperlipidaemia and insulin resistance that does not develop diabetes. NEFA augmentation of insulin secretion and fatty acid metabolism were studied in isolated islets from ZF and Zucker lean (ZL) control rats. Exogenous palmitate markedly potentiated glucose-stimulated insulin secretion (GSIS) in ZF islets, allowing robust secretion at physiological glucose levels (5-8 mmol/l). Exogenous palmitate also synergised with glucagon-like peptide-1 and the cyclic AMP-raising agent forskolin to enhance GSIS in ZF islets only. In assessing islet fatty acid metabolism, we found increased glucose-responsive palmitate esterification and lipolysis processes in ZF islets, suggestive of enhanced triglyceride-fatty acid cycling. Interruption of glucose-stimulated lipolysis by the lipase inhibitor Orlistat (tetrahydrolipstatin) blunted palmitate-augmented GSIS in ZF islets. Fatty acid oxidation was also higher at intermediate glucose levels in ZF islets and steatotic triglyceride accumulation was absent. The results highlight the potential importance of NEFA and glucoincretin enhancement of insulin secretion in beta cell compensation for insulin resistance. We propose that coordinated glucose-responsive fatty acid esterification and lipolysis processes, suggestive of triglyceride-fatty acid cycling, play a role in the coupling mechanisms of glucose-induced insulin secretion as well as in beta cell compensation and the hypersecretion of insulin in obesity.

Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

PubMed

Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

2011-06-01

Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes.

PubMed Central

Weinstock, P H; Bisgaier, C L; Aalto-Setälä, K; Radner, H; Ramakrishnan, R; Levak-Frank, S; Essenburg, A D; Zechner, R; Breslow, J L

1995-01-01

Lipoprotein lipase (LPL)-deficient mice have been created by gene targeting in embryonic stem cells. At birth, homozygous knockout pups have threefold higher triglycerides and sevenfold higher VLDL cholesterol levels than controls. When permitted to suckle, LPL-deficient mice become pale, then cyanotic, and finally die at approximately 18 h of age. Before death, triglyceride levels are severely elevated (15,087 +/- 3,805 vs 188 +/- 71 mg/dl in controls). Capillaries in tissues of homozygous knockout mice are engorged with chylomicrons. This is especially significant in the lung where marginated chylomicrons prevent red cell contact with the endothelium, a phenomenon which is presumably the cause of cyanosis and death in these mice. Homozygous knockout mice also have diminished adipose tissue stores as well as decreased intracellular fat droplets. By crossbreeding with transgenic mice expressing human LPL driven by a muscle-specific promoter, mouse lines were generated that express LPL exclusively in muscle but not in any other tissue. This tissue-specific LPL expression rescued the LPL knockout mice and normalized their lipoprotein pattern. This supports the contention that hypertriglyceridemia caused the death of these mice and that LPL expression in a single tissue was sufficient for rescue. Heterozygous LPL knockout mice survive to adulthood and have mild hypertriglyceridemia, with 1.5-2-fold elevated triglyceride levels compared with controls in both the fed and fasted states on chow, Western-type, or 10% sucrose diets. In vivo turnover studies revealed that heterozygous knockout mice had impaired VLDL clearance (fractional catabolic rate) but no increase in transport rate. In summary, total LPL deficiency in the mouse prevents triglyceride removal from plasma, causing death in the neonatal period, and expression of LPL in a single tissue alleviates this problem. Furthermore, half-normal levels of LPL cause a decrease in VLDL fractional catabolic rate and mild hypertriglyceridemia, implying that partial LPL deficiency has physiological consequences. Images PMID:8675619

Reduced circulating levels of sTWEAK are associated with NAFLD and may affect hepatocyte triglyceride accumulation.

PubMed

Lozano-Bartolomé, J; Llauradó, G; Rodriguez, M M; Fernandez-Real, J M; Garcia-Fontgivell, J F; Puig, J; Maymó-Masip, E; Vendrell, J; Chacón, M R

2016-09-01

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and is strongly associated with obesity, dyslipidaemia and altered glucose regulation. Previous data demonstrated that low circulating levels of tumour necrosis factor weak inducer of apoptosis (sTWEAK) were associated with obesity, diabetes and insulin resistance, all traits associated with an increased risk of NALFD. Circulating sTWEAK levels are expected to be reduced in the presence of NAFLD. We aimed to explore the relationship between NAFLD and circulating sTWEAK levels in obese patients, and to evaluate the effect of sTWEAK on hepatocyte triglyceride accumulation.Design setting and patients:This is an observational case-control study performed in n=112 severely obese patients evaluated for NAFLD by abdominal ultrasound and n=32 non-obese patients without steatosis. Serum sTWEAK concentrations were measured by ELISA. Multivariable analyses were performed to determine the independent predictors of NAFLD. We analysed TWEAK and Fn14 protein expression in liver biopsies by western blotting and immunohistochemistry. An immortalized primary human hepatocyte cell line (HHL) was used to evaluate the effect of sTWEAK on triglyceride accumulation. We observed a reduction in serum circulating sTWEAK concentrations with the presence of liver steatosis. On multivariable analysis, lower sTWEAK concentrations were independently associated with the presence of NAFLD (odds ratio (OR)=0.023; 95% confidence interval: 0.001-0.579; P<0.022). In human hepatocytes, sTWEAK administration reduced fat accumulation as demonstrated by the reduction in palmitic acid-induced accumulation of triglyceride and the decreased expression of cluster of differentiation 36 (CD36) and perilipin 1 and 2 (PLIN1 and PLIN2) genes. Decreased sTWEAK concentrations are independently associated with the presence of NAFLD. This is concordant with the observation that TWEAK reduces lipid accumulation in human liver cells.

Effects of Sugar-sweetened Beverages on plasma Acylation Stimulating Protein, Leptin & Adiponectin and Metabolic Parameters

PubMed Central

Rezvani, Reza; Cianflone, Katherine; McGahan, John P.; Berglund, Lars; Bremer, Andrew A.; Keim, Nancy L.; Griffen, Steven C.; Havel, Peter J.; Stanhope, Kimber L.

2013-01-01

Objective We determined the effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity. Design and Methods 32 overweight/obese adults consumed glucose- or fructose-sweetened beverages (25% energy requirement) with their ad libitum diets for 8 weeks, followed by sweetened beverage consumption for 2 weeks with a standardized, energy-balanced diet. Plasma variables were measured at baseline, 2, 8 and 10 weeks, and body adiposity and insulin sensitivity at baseline and 10 weeks. Results Fasting and postprandial ASP concentrations increased at 2 and/or 8 weeks. ASP increases correlated with changes in late-evening triglyceride concentrations. At 10 weeks, fasting adiponectin levels decreased in both groups, and decreases were inversely associated with baseline intra-abdominal fat volume. Sugar consumption increased fasting leptin concentrations; increases were associated with body weight changes. 24-h leptin profiles increased during glucose consumption and decreased during fructose consumption. These changes correlated with changes of 24-h insulin levels. Conclusions The consumption of fructose and glucose beverages induced changes in plasma concentrations of ASP, adiponectin and leptin. Further study is required to determine if these changes contribute to the metabolic dysfunction observed during fructose consumption. PMID:23512943

Physiological levels and action of dehydroepiandrosterone in Yucatan miniature swine.

PubMed

Tagliaferro, A R; Ronan, A M

2001-07-01

The biological role of dehydroepiandrosterone (DHEA) and its less active sulphated conjugate DHEAS was investigated in two experiments using Yucatan miniature swine. In experiment 1, plasma levels of both DHEA(S) among males were greater than female pigs that ranged in age from 0.3 to 84 mo old (P < 0.0001). In males, DHEA(S) were related inversely to serum triglycerides; DHEA was positively related to triglycerides in females (P < 0.01). In experiment 2, four 2-yr old male pigs, used as their own control, showed a 5% decrease in body weight, 11% increase in energy expenditure, 88% increase in lipid, and 100% decrease in glucose utilization (P < 0.0001) in response to DHEA vs. placebo treatments when adjusted for body weight. Plasma DHEA(S) were not different between treatment conditions. Glucose tolerance and plasma insulin levels were not different from controls. In vivo response to norepinephrine indicated beta-adrenergic sensitivity was altered by DHEA. Present findings suggest DHEA and/or its hormone products are important in modulating energy expenditure and lipid utilization for energy in male animals. The role of DHEA in energy metabolism and the difference between sexes warrant further investigation.

Beneficial effects of coconut water feeding on lipid metabolism in cholesterol-fed rats.

PubMed

Sandhya, V G; Rajamohan, T

2006-01-01

The purpose of this study was to determine the effect of coconut water feeding in cholesterol-fed rats. Male albino rats were fed tender coconut water and mature coconut water at a dose level of 4 mL/100 g of body weight. Cholesterol feeding caused a marked increase in total cholesterol, very low-density lipoprotein (VLDL) + low-density lipoprotein (LDL) cholesterol, and triglycerides in serum. Administration of coconut water counteracts the increase in total cholesterol, VLDL + LDL cholesterol, and triglycerides, while high-density lipoprotein cholesterol was higher. Lipid levels in the tissues viz. liver, heart, kidney, and aorta were markedly decreased in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased activities of 3-hydroxy-3-methylglutaryl-CoA reductase in liver, lipoprotein lipase in heart and adipose tissue, and plasma lecithin:cholesterol acyl transferase, while lipogenic enzymes showed decreased activities. An increased rate of cholesterol conversion to bile acid and an increased excretion of bile acids and neutral sterols were observed in rats fed coconut water. Histopathological studies of liver and aorta revealed much less fatty accumulation in these tissues in cholesterol-fed rats supplemented with coconut water. Feeding coconut water resulted in increased plasma L-arginine content, urinary nitrite level, and nitric oxide synthase activity. These results indicate that both tender and mature coconut water has beneficial effects on serum and tissue lipid parameters in rats fed cholesterol-containing diet.

Relationship between Triglyceride and HDL-C ratio with Acute Coronary Syndrome.

PubMed

Islam, M Z; Islam, M N; Bhowmik, T K; Saha, B; Hossain, M S; Ahmed, H; Ali, M S; Shakil, S S; Paul, P K

2018-04-01

Cardiovascular diseases (CVD) is the leading cause of death worldwide, responsible for one third of death, coronary artery disease (CAD) is the most common cause. Dyslipidaemiais one of the major contributors increased of CAD risk. This study was aimed to find out the relationship between triglyceride and HDL cholesterol ratio with acute coronary syndrome. This cross sectional study was conducted in the department of Cardiology, Mymensingh Medical College Hospital from August 2009 to May 2010. Smoking, hypertension, serum total cholesterol level, serum HDL-C, LDL-C, triglyceride (TG) level were important variable considered. A total number of 100 respondents consisted of 50 cases (patient) and 50 healthy persons (control). Investigations included ECG, Troponin-I, FBS and lipid profile. The data was analyzed by computer with the help of SPSS; Chi-square test, 't' test, ANOVA test used as test of significance. The mean level in cases of TG 168.2±88.0 vs. HDL 41.3±5.1 in control level TG 141.2±45.3 and HDL 34.2±3.4. TG/HDL ratio cases 4.2±1.7 and control 4.1±1.3. This ratio >4 is atherogenic for CAD. Unadjusted odds ratio TG/HDL ratio level high (>1). In multivariable regression analysis, TG/HDL ratio was strong relation with ACS. The study reflected that high TG/HDL ratio is associated with ACS. Categorization of patient with ACS on the basis of high TG/HDL ratio will be helpful for risk stratification and management.

Differential Responses of Plasma Adropin Concentrations To Dietary Glucose or Fructose Consumption In Humans.

PubMed

Butler, Andrew A; St-Onge, Marie-Pierre; Siebert, Emily A; Medici, Valentina; Stanhope, Kimber L; Havel, Peter J

2015-10-05

Adropin is a peptide hormone encoded by the Energy Homeostasis Associated (ENHO) gene whose physiological role in humans remains incompletely defined. Here we investigated the impact of dietary interventions that affect systemic glucose and lipid metabolism on plasma adropin concentrations in humans. Consumption of glucose or fructose as 25% of daily energy requirements (E) differentially affected plasma adropin concentrations (P < 0.005) irrespective of duration, sex or age. Glucose consumption reduced plasma adropin from 3.55 ± 0.26 to 3.28 ± 0.23 ng/ml (N = 42). Fructose consumption increased plasma adropin from 3.63 ± 0.29 to 3.93 ± 0.34 ng/ml (N = 45). Consumption of high fructose corn syrup (HFCS) as 25% E had no effect (3.43 ± 0.32 versus 3.39 ± 0.24 ng/ml, N = 26). Overall, the effect of glucose, HFCS and fructose on circulating adropin concentrations were similar to those observed on postprandial plasma triglyceride concentrations. Furthermore, increases in plasma adropin levels with fructose intake were most robust in individuals exhibiting hypertriglyceridemia. Individuals with low plasma adropin concentrations also exhibited rapid increases in plasma levels following consumption of breakfasts supplemented with lipids. These are the first results linking plasma adropin levels with dietary sugar intake in humans, with the impact of fructose consumption linked to systemic triglyceride metabolism. In addition, dietary fat intake may also increase circulating adropin concentrations.

DGAT and triglyceride synthesis: a new target for obesity treatment?

PubMed

Chen, H C; Farese, R V

2000-07-01

Because triglycerides are considered essential for survival and their synthesis has been thought to occur through a single mechanism, inhibiting triglyceride synthesis has been largely unexplored as a possible target for obesity treatment. However, recent studies indicate that mice lacking acyl CoA:diacylglycerol acyltransferase (DGAT), a key enzyme in triglyceride synthesis, are viable and resistant to diet-induced obesity. Unexpectedly, this resistance is caused by a mechanism involving increased energy expenditure. These findings suggest that inhibiting specific components of triglyceride synthesis, such as DGAT, is feasible and may represent a novel approach to treating obesity.

Quality performance of laboratory testing in pharmacies: a collaborative evaluation.

PubMed

Zaninotto, Martina; Miolo, Giorgia; Guiotto, Adriano; Marton, Silvia; Plebani, Mario

2016-11-01

The quality performance and the comparability between results of pharmacies point-of-care-testing (POCT) and institutional laboratories have been evaluated. Eight pharmacies participated in the project: a capillary specimen collected by the pharmacist and, simultaneously, a lithium-heparin sample drawn by a physician of laboratory medicine for the pharmacy customers (n=106) were analyzed in the pharmacy and in the laboratory, respectively. Glucose, cholesterol, HDL-cholesterol, triglycerides, creatinine, uric acid, aspartate aminotransferase, alanine aminotransferase, were measured using: Reflotron, n=5; Samsung, n=1; Cardiocheck PA, n=1; Cholestech LDX, n=1 and Cobas 8000. The POCT analytical performance only (phase 2) were evaluated testing, in pharmacies and in the laboratory, the lithium heparin samples from a female drawn fasting daily in a week, and a control sample containing high concentrations of glucose, cholesterol and triglycerides. For all parameters, except triglycerides, the slopes showed a satisfactory correlation. For triglycerides, a median value higher in POCT in comparison to the laboratory (1.627 mmol/L vs. 0.950 mmol/L) has been observed. The agreement in the subjects classification, demonstrates that for glucose, 70% of the subjects show concentrations below the POCT recommended level (5.8-6.1 mmol/L), while 56% are according to the laboratory limit (<5.6 mmol/L). Total cholesterol exhibits a similar trend while POCT triglycerides show a greater percentage of increased values (21% vs. 9%). The reduction in triglycerides bias (phase 2) suggests that differences between POCT and central laboratory is attributable to a pre-analytical problem. The results confirm the acceptable analytical performance of POCT pharmacies and specific criticisms in the pre- and post-analytical phases.

Carbon and Acyl Chain Flux during Stress-induced Triglyceride Accumulation by Stable Isotopic Labeling of the Polar Microalga Coccomyxa subellipsoidea C169*

PubMed Central

Allen, James W.; DiRusso, Concetta C.; Black, Paul N.

2017-01-01

Deriving biofuels and other lipoid products from algae is a promising future technology directly addressing global issues of atmospheric CO2 balance. To better understand the metabolism of triglyceride synthesis in algae, we examined their metabolic origins in the model species, Coccomyxa subellipsoidea C169, using stable isotopic labeling. Labeling patterns arising from [U-13C]glucose, 13CO2, or D2O supplementation were analyzed by GC-MS and/or LC-MS over time courses during nitrogen starvation to address the roles of catabolic carbon recycling, acyl chain redistribution, and de novo fatty acid (FA) synthesis during the expansion of the lipid bodies. The metabolic origin of stress-induced triglyceride was found to be a continuous 8:2 ratio between de novo synthesized FA and acyl chain transfer from pre-stressed membrane lipids with little input from lipid remodeling. Membrane lipids were continually synthesized with associated acyl chain editing during nitrogen stress, in contrast to an overall decrease in total membrane lipid. The incorporation rates of de novo synthesized FA into lipid classes were measured over a time course of nitrogen starvation. The synthesis of triglycerides, phospholipids, and galactolipids followed a two-stage pattern where nitrogen starvation resulted in a 2.5-fold increase followed by a gradual decline. Acyl chain flux into membrane lipids was dominant in the first stage followed by triglycerides. These data indicate that the level of metabolic control that determines acyl chain flux between membrane lipids and triglycerides during nitrogen stress relies primarily on the Kennedy pathway and de novo FA synthesis with limited, defined input from acyl editing reactions. PMID:27903654

Carbon and Acyl Chain Flux during Stress-induced Triglyceride Accumulation by Stable Isotopic Labeling of the Polar Microalga Coccomyxa subellipsoidea C169.

PubMed

Allen, James W; DiRusso, Concetta C; Black, Paul N

2017-01-06

Deriving biofuels and other lipoid products from algae is a promising future technology directly addressing global issues of atmospheric CO 2 balance. To better understand the metabolism of triglyceride synthesis in algae, we examined their metabolic origins in the model species, Coccomyxa subellipsoidea C169, using stable isotopic labeling. Labeling patterns arising from [U- 13 C]glucose, 13 CO 2 , or D 2 O supplementation were analyzed by GC-MS and/or LC-MS over time courses during nitrogen starvation to address the roles of catabolic carbon recycling, acyl chain redistribution, and de novo fatty acid (FA) synthesis during the expansion of the lipid bodies. The metabolic origin of stress-induced triglyceride was found to be a continuous 8:2 ratio between de novo synthesized FA and acyl chain transfer from pre-stressed membrane lipids with little input from lipid remodeling. Membrane lipids were continually synthesized with associated acyl chain editing during nitrogen stress, in contrast to an overall decrease in total membrane lipid. The incorporation rates of de novo synthesized FA into lipid classes were measured over a time course of nitrogen starvation. The synthesis of triglycerides, phospholipids, and galactolipids followed a two-stage pattern where nitrogen starvation resulted in a 2.5-fold increase followed by a gradual decline. Acyl chain flux into membrane lipids was dominant in the first stage followed by triglycerides. These data indicate that the level of metabolic control that determines acyl chain flux between membrane lipids and triglycerides during nitrogen stress relies primarily on the Kennedy pathway and de novo FA synthesis with limited, defined input from acyl editing reactions. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Age- and Gender-Specific Reference Intervals for Fasting Blood Glucose and Lipid Levels in School Children Measured With Abbott Architect c8000 Chemistry Analyzer.

PubMed

Tamimi, Waleed; Albanyan, Esam; Altwaijri, Yasmin; Tamim, Hani; Alhussein, Fahad

2012-04-01

Reference intervals for pubertal characteristics are influenced by genetic, geographic, dietary and socioeconomic factors. Therefore, the aim of this study was to establish age-specific reference intervals of glucose and lipid levels among local school children. This was cross-sectional study, conducted among Saudi school children. Fasting blood samples were collected from 2149 children, 1138 (53%) boys and 1011 (47%) girls, aged 6 to 18 years old. Samples were analyzed on the Architect c8000 Chemistry System (Abbott Diagnostics, USA) for glucose, cholesterol, triglycerides, HDL and LDL. Reference intervals were established by nonparametric methods between the 2.5th and 97.5th percentiles. Significant differences were observed between boys and girls for cholesterol and triglycerides levels in all age groups (P < 0.02). Only at age 6-7 years and at adolescents, HDL and LDL levels were found to be significant (P < 0.001). No significant differences were seen in glucose levels except at age 12 to 13 years. Saudi children have comparable serum cholesterol levels than their Western counterparts. This may reflect changing dietary habits and increasing affluence in Saudi Arabia. Increased lipid screening is anticipated, and these reference intervals will aid in the early assessment of cardiovascular and diabetes risk in Saudi pediatric populations.

Triglycerides and small dense low density lipoprotein in the discrimination of coronary heart disease risk in South Asian populations.

PubMed

Patel, J V; Caslake, M J; Vyas, A; Cruickshank, J K; Prabhakaran, D; Bhatnagar, D; Reddy, K S; Lip, G Y H; Mackness, M I; Hughes, E A; Durrington, P N

2010-04-01

Coronary heart disease (CHD) is exceptionally prevalent amongst globally dispersed migrant groups originating from the Indian subcontinent, but the contribution of dyslipidaemia to their increased risk remains poorly defined. Fasting lipids and lipoproteins, apolipoproteins (Apo), low density lipoprotein (LDL) diameter and oxidised LDL were measured amongst rural Indians in India (n=294) and their migrant contemporaries in the UK (n=242). The performance of qualitative and quantitative measures of lipid metabolism were compared in the discrimination of WHO defined metabolic risk and raised Framingham CHD risk scores (>15%) using Receiver Operating Characteristic (ROC) curves. LDL diameter was correlated with triglycerides (R(2)=0.12, P<0.001) and with high density lipoprotein (HDL) cholesterol levels (R(2)=0.15, P<0.001) in both groups. Migrants had less small dense LDL (95% CI: 12.5-14.2%) vs. rural Indians (15.7-17.2, P<0.05). On ROC analysis, triglycerides were the only consistent discriminators of metabolic and CHD risk scores (all P< or =0.001). Apo B was also a strong indicator of raised CHD risk scores. Irrespective of site, individuals with raised triglycerides also had higher total cholesterol and Apo B, denser LDL, lower HDL and more oxidised LDL (all P< or =0.01). Fasting triglycerides reflect both qualitative and quantitative aspects of lipid metabolism, and are a comprehensive discriminator of CHD risk in this South Asian population. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

Effects of cumin extract on oxLDL, paraoxanase 1 activity, FBS, total cholesterol, triglycerides, HDL-C, LDL-C, Apo A1, and Apo B in in the patients with hypercholesterolemia

PubMed Central

Samani, Keihan Ghatreh; Farrokhi, Effat

2014-01-01

Objectives Paraoxanase 1 (PON1) plays a protective role against the oxidative modification of plasma lipoproteins and hydrolyzes lipid peroxides in human atherosclerotic lesions. Cumin is the dried seed of the herb Cuminumcyminum that is known as Zeera in Iran. Cumin seeds contain flavonoids which are now generally recognized to have antioxidant activity and improve the antioxidant system. So, they possibly modify PON1 activity and oxidized low density lipoprotein (oxLDL) level. The present study was aimed to evaluate the effects of cumin extract supplementation on oxLDL, paraoxanase 1 activity, FBS, total cholesterol, triglycerides, High density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B)in the patients with hypercholesterolemia. Methodology A fasting venous blood sample was obtained from the voluntary persons before and 45±3 days after taking cumin. Glucose, total cholesterol, and triglycerides were assayed using standard enzymatic procedures. HDL-Cand LDL-C were measured by direct method and ApoA1 and ApoB levels by immunoturbidimeteric methods. The levels of arylesterase and paraoxanase activities in the samples were measured by photometry methods and oxLDL by enzyme-linked immunosorbent assay (ELISA) method. 3 to 5 drops of cumin extract were added to the patient’s diet three times a day based on manufacturer’s instruction for 45±3 days. The biochemical parameters were compared before and after taking cumin. Data were analyzed using paired Student’s t-test in SPSS statistical software (version 11.5). Results The results demonstrated that there was a significant decrease in the level of oxLDL after receiving cumin. Paraoxonase and arylesterase activities increased in serum after taking cumin extract. Conclusion Based on the results, cumin reduces oxLDL level and increases both paraoxonase and arylesterase activity. PMID:24899878

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.

Psychological well-being and restorative biological processes: HDL-C in older English adults.

PubMed

Soo, Jackie; Kubzansky, Laura D; Chen, Ying; Zevon, Emily S; Boehm, Julia K

2018-05-14

Psychological well-being is associated with better cardiovascular health, but the underlying mechanisms are unclear. This study investigates one possible mechanism by examining psychological well-being's prospective association with lipid levels, focusing on high-density lipoprotein cholesterol (HDL-C). Participants were 4757 healthy men and women ages ≥50 from the English Longitudinal Study of Ageing with clinical data from three times, three to five years apart. Psychological well-being was assessed at baseline using the Control, Autonomy, Satisfaction, and Pleasure scale; HDL-C, triglycerides, and total cholesterol were assayed from blood samples. Descriptive statistics and linear mixed models were used to examine associations between psychological well-being and lipid levels over time; the latter controlled for confounders and health behaviours. In descriptive analyses, HDL-C levels were initially higher in people with greater psychological well-being. Among those who met recommended levels of HDL-C at baseline, fewer individuals with higher versus lower psychological well-being dropped below HDL-C recommendations over time. Mixed models indicated that HDL-C increased over time (β = 0.64; 95% CI = 0.58 to 0.69) and higher baseline psychological well-being was associated with higher baseline HDL-C (β = 0.51; 95% CI = 0.03 to 0.99). A significant well-being by time interaction indicated individuals with higher versus lower well-being exhibited a more rapid rate of increase in HDL-C over follow-up. Higher psychological well-being was also significantly associated with lower triglycerides, but main effects for both HDL-C and triglycerides were attenuated after accounting for health behaviours. Higher psychological well-being is associated with healthier HDL-C levels; these effects may compound over time. This protective effect may be partly explained by health behaviours. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides.

PubMed

Rayner, Katey J; Esau, Christine C; Hussain, Farah N; McDaniel, Allison L; Marshall, Stephanie M; van Gils, Janine M; Ray, Tathagat D; Sheedy, Frederick J; Goedeke, Leigh; Liu, Xueqing; Khatsenko, Oleg G; Kaimal, Vivek; Lees, Cynthia J; Fernandez-Hernando, Carlos; Fisher, Edward A; Temel, Ryan E; Moore, Kathryn J

2011-10-19

Cardiovascular disease remains the leading cause of mortality in westernized countries, despite optimum medical therapy to reduce the levels of low-density lipoprotein (LDL)-associated cholesterol. The pursuit of novel therapies to target the residual risk has focused on raising the levels of high-density lipoprotein (HDL)-associated cholesterol in order to exploit its atheroprotective effects. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of lipid metabolism and are thus a new class of target for therapeutic intervention. MicroRNA-33a and microRNA-33b (miR-33a/b) are intronic miRNAs whose encoding regions are embedded in the sterol-response-element-binding protein genes SREBF2 and SREBF1 (refs 3-5), respectively. These miRNAs repress expression of the cholesterol transporter ABCA1, which is a key regulator of HDL biogenesis. Recent studies in mice suggest that antagonizing miR-33a may be an effective strategy for raising plasma HDL levels and providing protection against atherosclerosis; however, extrapolating these findings to humans is complicated by the fact that mice lack miR-33b, which is present only in the SREBF1 gene of medium and large mammals. Here we show in African green monkeys that systemic delivery of an anti-miRNA oligonucleotide that targets both miR-33a and miR-33b increased hepatic expression of ABCA1 and induced a sustained increase in plasma HDL levels over 12 weeks. Notably, miR-33 antagonism in this non-human primate model also increased the expression of miR-33 target genes involved in fatty acid oxidation (CROT, CPT1A, HADHB and PRKAA1) and reduced the expression of genes involved in fatty acid synthesis (SREBF1, FASN, ACLY and ACACA), resulting in a marked suppression of the plasma levels of very-low-density lipoprotein (VLDL)-associated triglycerides, a finding that has not previously been observed in mice. These data establish, in a model that is highly relevant to humans, that pharmacological inhibition of miR-33a and miR-33b is a promising therapeutic strategy to raise plasma HDL and lower VLDL triglyceride levels for the treatment of dyslipidaemias that increase cardiovascular disease risk.

Diet-induced effects on neuronal and glial elements in the middle-aged rat hippocampus

PubMed Central

Freeman, Linnea R.; Haley-Zitlin, Vivian; Stevens, Cheryl; Granholm, Ann-Charlotte

2014-01-01

Consumption of a high-fat and/or high-cholesterol diet can have detrimental effects on the brain. In the present study, dietary treatment with saturated fats, trans fats, or cholesterol to middle-aged Fischer 344 rats resulted in alterations to serum triglyceride and cholesterol levels, organ weights, and hippocampal morphology. Previously, we demonstrated that a 10% hydrogenated coconut oil and 2% cholesterol diet resulted in worse performance on the 12-day water radial arm maze, increased cholesterol and triglyceride levels, and decreased dendritic microtubule associated protein 2 (MAP2) staining in the hippocampus. The diets administered herein were used to examine components from the previous diet and further examine their effects on hippocampal morphology. Specifically, neuronal morphology, dendritic integrity, fatty acid metabolism, microgliosis, and blood vessel structure in the hippocampus and/or adjacent structures were explored. Our results indicate alterations to peripheral and neural systems following each of the diets. PMID:21535919

Early Emergence of Ethnic Differences in Type 2 Diabetes Precursors in the UK: The Child Heart and Health Study in England (CHASE Study)

PubMed Central

Whincup, Peter H.; Nightingale, Claire M.; Owen, Christopher G.; Rudnicka, Alicja R.; Gibb, Ian; McKay, Catherine M.; Donin, Angela S.; Sattar, Naveed; Alberti, K. George M. M.; Cook, Derek G.

2010-01-01

Background Adults of South Asian origin living in the United Kingdom have high risks of type 2 diabetes and central obesity; raised circulating insulin, triglyceride, and C-reactive protein concentrations; and low HDL-cholesterol when compared with white Europeans. Adults of African-Caribbean origin living in the UK have smaller increases in type 2 diabetes risk, raised circulating insulin and HDL-cholesterol, and low triglyceride and C-reactive protein concentrations. We examined whether corresponding ethnic differences were apparent in childhood. Methods and Findings We performed a cross-sectional survey of 4,796 children aged 9–10 y in three UK cities who had anthropometric measurements (68% response) and provided blood samples (58% response); ethnicity was based on parental definition. In age-adjusted comparisons with white Europeans (n = 1,153), South Asian children (n = 1,306) had higher glycated haemoglobin (HbA1c) (% difference: 2.1, 95% CI 1.6 to 2.7), fasting insulin (% difference 30.0, 95% CI 23.4 to 36.9), triglyceride (% difference 12.9, 95% CI 9.4 to 16.5), and C-reactive protein (% difference 43.3, 95% CI 28.6 to 59.7), and lower HDL-cholesterol (% difference −2.9, 95% CI −4.5 to −1.3). Higher adiposity levels among South Asians (based on skinfolds and bioimpedance) did not account for these patterns. Black African-Caribbean children (n = 1,215) had higher levels of HbA1c, insulin, and C-reactive protein than white Europeans, though the ethnic differences were not as marked as in South Asians. Black African-Caribbean children had higher HDL-cholesterol and lower triglyceride levels than white Europeans; adiposity markers were not increased. Conclusions Ethnic differences in type 2 diabetes precursors, mostly following adult patterns, are apparent in UK children in the first decade. Some key determinants operate before adult life and may provide scope for early prevention. Please see later in the article for the Editors' Summary PMID:20421924

The role of red dragon fruit peel (Hylocereus polyrhizus) to improvement blood lipid levels of hyperlipidaemia male mice

NASA Astrophysics Data System (ADS)

Hernawati; Setiawan, N. A.; Shintawati, R.; Priyandoko, D.

2018-05-01

The purpose of this research was to know the role of red dragon fruit peel powder to total cholesterol, triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and weight in the male hyperlipidaemic Balb-C mice (Mus musculus). This study used a completely randomized design (CRD) and four replicates for each dose treatments. Samples were 24 male mice that divided into six groups i.e. positive and negative controls, doses of 50; 100; 150 and 200 mg/kgBW/days red dragon fruit peel powder. Before being given treatment, mice were given feed containing high fat for 20 days until experiencing conditions hyperlipidaemia. The red dragon fruit peel powder was given at oral with used gavage for 30 days. Blood samples were taken from the tail on vena caudalis. Blood lipid samples were analysed at enzymatic with BIOLABO kits. The results of this study indicate that after administration of red dragon fruit peel powder total cholesterol levels, triglycerides and LDL-c decreased, along with increasing doses of red dragon fruit peel powder for 30 days. Furthermore showed that dragon fruit powder can increase HDL-c levels. The conclusion of this research was The red dragon fruit peel powder can improve blood lipid level of male Balb-c mice hyperlipidaemia.

Effects of Inhibition of Interleukin-6 Signalling on Insulin Sensitivity and Lipoprotein (A) Levels in Human Subjects with Rheumatoid Diseases

PubMed Central

Schultz, Olaf; Oberhauser, Frank; Saech, Jasemine; Rubbert-Roth, Andrea; Hahn, Moritz; Krone, Wilhelm; Laudes, Matthias

2010-01-01

Background Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab. Methodology/Principal Findings 11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a) (Lp (a)) were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a) levels significantly decreased. Conclusions/Significance Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a) serum levels, which might reduce the cardiovascular risk of human subjects. PMID:21179199

Mild hypercholesterolemia, normal plasma triglycerides, and normal glucose levels across dementia staging in Alzheimer's disease: a clinical setting-based retrospective study.

PubMed

Ramdane, Said; Daoudi-Gueddah, Doria

2011-08-01

We examined retrospectively the concurrent relationships between fasting plasma total cholesterol, triglycerides, and glucose levels, and Alzheimer's disease (AD), in a clinical setting-based study. Total cholesterol level was higher in patients with AD compared to elderly controls; triglycerides or glucose levels did not significantly differ between the 2 groups. Respective plotted trajectories of change in cholesterol level across age were fairly parallel. No significant difference in total cholesterol levels was recorded between patients with AD classified by the Clinical Dementia Rating (CDR) score subgroups. These results suggest that patients with AD have relative mild total hypercholesterolemia, normal triglyceridemia, and normal fasting plasma glucose level. Mild total hypercholesterolemia seems to be permanent across age, and across dementia severity staging, and fairly parallels the trajectory of age-related change in total cholesterolemia of healthy controls. We speculate that these biochemical parameters pattern may be present long before-a decade at least-the symptomatic onset of the disease.

Economic insecurity during the Great Recession and metabolic, inflammatory and liver function biomarkers: analysis of the UK Household Longitudinal Study

PubMed Central

Niedzwiedz, Claire L; Katikireddi, Srinivasa Vittal; Reeves, Aaron; McKee, Martin; Stuckler, David

2017-01-01

Background Economic insecurity correlates with adverse health outcomes, but the biological pathways involved are not well understood. We examine how changes in economic insecurity relate to metabolic, inflammatory and liver function biomarkers. Methods Blood analyte data were taken from 6520 individuals (aged 25–59 years) participating in Understanding Society. Economic insecurity was measured using an indicator of subjective financial strain and by asking participants whether they had missed any bill, council tax, rent or mortgage payments in the past year. We investigated longitudinal changes in economic insecurity (remained secure, increase in economic insecurity, decrease in economic insecurity, remained insecure) and the accumulation of economic insecurity. Linear regression models were calculated for nine (logged) biomarker outcomes related to metabolic, inflammatory, liver and kidney function (as falsification tests), adjusting for potential confounders. Results Compared with those who remained economically stable, people who experienced consistent economic insecurity (using both measures) had worsened levels of high-density lipoprotein (HDL)-cholesterol, triglycerides, C reactive protein (CRP), fibrinogen and glycated haemoglobin. Increased economic insecurity was associated with adverse levels of HDL-cholesterol (0.955, 95% CI 0.929 to 0.982), triglycerides (1.077, 95% CI 1.018 to 1.139) and CRP (1.114, 95% CI 1.012 to 1.227), using the measure of financial strain. Results for the other measure were generally consistent, apart from the higher levels of gamma-glutamyl transferase observed among those experiencing persistent insecurity (1.200, 95% CI 1.110 to 1.297). Conclusion Economic insecurity is associated with adverse metabolic and inflammatory biomarkers (particularly HDL-cholesterol, triglycerides and CRP), heightening risk for a range of health conditions. PMID:28855264

The adaptor protein alpha-syntrophin regulates adipocyte lipid droplet growth

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

Eisinger, Kristina; Rein-Fischboeck, Lisa; Pohl, Rebekka

The scaffold protein alpha-syntrophin (SNTA) regulates lipolysis indicating a role in lipid homeostasis. Adipocytes are the main lipid storage cells in the body, and here, the function of SNTA has been analyzed in 3T3-L1 cells. SNTA is expressed in preadipocytes and is induced early during adipogenesis. Knock-down of SNTA in preadipocytes increases their proliferation. Proteins which are induced during adipogenesis like adiponectin and caveolin-1, and the inflammatory cytokine IL-6 are at normal levels in the mature cells differentiated from preadipocytes with low SNTA. This suggests that SNTA does neither affect differentiation nor inflammation. Expression of proteins with a role inmore » cholesterol and triglyceride homeostasis is unchanged. Consequently, basal and epinephrine induced lipolysis as well as insulin stimulated phosphorylation of Akt and ERK1/2 are normal. Importantly, adipocytes with low SNTA form smaller lipid droplets and store less triglycerides. Stearoyl-CoA reductase and MnSOD are reduced upon SNTA knock-down but do not contribute to lower lipid levels. Oleate uptake is even increased in cells with SNTA knock-down. In summary, current data show that SNTA is involved in the expansion of lipid droplets independent of adipogenesis. Enhanced preadipocyte proliferation and capacity to store surplus fatty acids may protect adipocytes with low SNTA from lipotoxicity in obesity. - Highlights: • Alpha-syntrophin (SNTA) is expressed in 3T3-L1adipocytes. • SNTA knock-down in preadipocytes has no effect on adipogenesis. • Mature 3T3-L1 differentiated from cells with low SNTA form small lipid droplets. • SCD1 and MnSOD are reduced in adipocytes with low SNTA. • SCD1 knock-down does not alter triglyceride levels.« less

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.

Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials).

PubMed

Mosca, Lori; Ballantyne, Christie M; Bays, Harold E; Guyton, John R; Philip, Sephy; Doyle, Ralph T; Juliano, Rebecca A

2017-02-01

There are limited data on the efficacy and safety of triglyceride (TG)-lowering agents in women. We conducted subgroup analyses of the effects of icosapent ethyl (a high-purity prescription form of the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid) on TG levels (primary efficacy variable) and other atherogenic and inflammatory parameters in a total of 215 women with a broad range of TG levels (200-2000 mg/dl) enrolled in two 12-week placebo-controlled trials: MARINE (n = 18; placebo, n = 18) and ANCHOR (n = 91; placebo, n = 88). Icosapent ethyl 4 g/day significantly reduced TG levels from baseline to week 12 versus placebo in both MARINE (-22.7%; p = 0.0327) and ANCHOR (-21.5%; p <0.0001) without increasing low-density lipoprotein cholesterol levels. Significant improvements were also observed in non-high-density lipoprotein cholesterol levels in MARINE (-15.7%; p = 0.0082) and ANCHOR (-14.2%; p <0.0001) and total cholesterol levels in MARINE (-14.9%; p = 0.0023) and ANCHOR (-12.1%; p <0.0001), along with significant increases of >500% in eicosapentaenoic acid levels in plasma and red blood cells (all p <0.001). Icosapent ethyl was well tolerated, with adverse-event profiles comparable with findings in the overall studies. In conclusion, icosapent ethyl 4 g/day significantly reduced TG levels and other atherogenic parameters in women without increasing low-density lipoprotein cholesterol levels compared with placebo; the clinical implications of these findings are being evaluated in the REDUCtion of Cardiovascular Events With Eicosapentaenoic Acid [EPA]-Intervention Trial (REDUCE-IT) cardiovascular outcomes study. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice.

PubMed

Li, B; Nolte, L A; Ju, J S; Han, D H; Coleman, T; Holloszy, J O; Semenkovich, C F

2000-10-01

To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle. Skeletal muscle oxygen consumption was 98% higher in Ucp-L mice (with low expression) and 246% higher in Ucp-H mice (with high expression) than in wild-type mice. Ucp mice fed a chow diet had the same food intake as wild-type mice, but weighed less and had lower levels of glucose and triglycerides and better glucose tolerance than did control mice. Ucp-L mice were resistant to obesity induced by two different high-fat diets. Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise. They were also more responsive to insulin, and had enhanced glucose transport in skeletal muscle in the setting of increased muscle triglyceride content. These data suggest that manipulating respiratory uncoupling in muscle is a viable treatment for obesity and its metabolic sequelae.

Insulin-loaded W/O/W multiple emulsions: comparison of the performances of systems prepared with medium-chain-triglycerides and fish oil.

PubMed

Cournarie, Fabienne; Savelli, Marie-Pierre; Rosilio, Véronique; Bretez, Françoise; Vauthier, Christine; Grossiord, Jean-Louis; Seiller, Monique

2004-11-01

Insulin-loaded W/O/W multiple emulsions (ME) composed of medium-chain triglycerides have been shown to decrease the blood glucose level after oral administration to diabetic rats. Fish oil (very long-chain triglycerides) could be an alternative to medium-chain triglycerides because its chronic consumption has beneficial therapeutic effects. The aim of this work was twofold: to obtain stable fish oil containing ME, based on a formulation optimized in a previous work with low medium-chain triglycerides content, and to compare their characteristics to those of ME composed of medium-chain triglycerides. Due to the higher viscosity and surface tension of fish oil compared to medium-chain triglycerides, preparation of ME appeared difficult to achieve. However, a stable unloaded-ME with low fish oil content was formed, by adapting the emulsification process. The characteristics of unloaded fish oil ME were almost similar to those of medium-chain triglycerides ME. In contrast to medium-chain triglycerides ME, the introduction of insulin did not improve the elasticity and consequently the characteristics and stability of fish oil ME. Nevertheless, the insulin-loaded fish oil containing ME was shown to be stable for 6 weeks at 4 degrees C.

Engineering E. coli for triglyceride accumulation through native and heterologous metabolic reactions.

PubMed

Rucker, Joanna; Paul, Julie; Pfeifer, Blaine A; Lee, Kyongbum

2013-03-01

Triglycerides, traditionally sourced from plant oils, are heavily used in both industrial and healthcare applications. Commercially significant products produced from triglycerides include biodiesel, lubricants, moisturizers, and oils for cooking and dietary supplements. The need to rely upon plant-based production, however, raises concerns of increasing demand and sustainability. The reliance on crop yields and a strong demand for triglycerides provides motivation to engineer production from a robust microbial platform. In this study, Escherichia coli was engineered to synthesize and accumulate triglycerides. Triglycerides were produced from cell wall phospholipid precursors through engineered expression of two enzymes, phosphatidic acid phosphatase (PAP) and diacylglycerol acyltransferase (DGAT). A liquid chromatography-mass spectrometry (LC-MS) method was developed to analyze the production of triglycerides by the engineered E. coli strains. This proof-of-concept study demonstrated a yield of 1.1 mg/L triglycerides (2 g/L dry cell weight) in lysogeny broth medium containing 5 g/L glucose at 8 h following induction of PAP and DGAT expression. LC-MS results also demonstrated that the intracellular triglyceride composition of E. coli was highly conserved. Triglycerides containing the fatty acid distributions 16:0/16:0/16:1, 16:0/16:0/18:1, and 18:1/16:0/16:1 were found in highest concentrations and represent ∼70 % of triglycerides observed.

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats

PubMed Central

Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

2011-01-01

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

Investigation of variants identified in caucasian genome-wide association studies for plasma high-density lipoprotein cholesterol and triglycerides levels in Mexican dyslipidemic study samples.

PubMed

Weissglas-Volkov, Daphna; Aguilar-Salinas, Carlos A; Sinsheimer, Janet S; Riba, Laura; Huertas-Vazquez, Adriana; Ordoñez-Sánchez, Maria L; Rodriguez-Guillen, Rosario; Cantor, Rita M; Tusie-Luna, Teresa; Pajukanta, Päivi

2010-02-01

Although epidemiological studies have demonstrated an increased predisposition to low high-density lipoprotein cholesterol and high triglyceride levels in the Mexican population, Mexicans have not been included in any of the previously reported genome-wide association studies for lipids. We investigated 6 single-nucleotide polymorphisms associated with triglycerides, 7 with high-density lipoprotein cholesterol, and 1 with both triglycerides and high-density lipoprotein cholesterol in recent Caucasian genome-wide association studies in Mexican familial combined hyperlipidemia families and hypertriglyceridemia case-control study samples. These variants were within or near the genes ABCA1, ANGPTL3, APOA5, APOB, CETP, GALNT2, GCKR, LCAT, LIPC, LPL (2), MMAB-MVK, TRIB1, and XKR6-AMAC1L2. We performed a combined analysis of the family-based and case-control studies (n=2298) using the Z method to combine statistics. Ten of the single-nucleotide polymorphisms were nominally significant and 5 were significant after Bonferroni correction (P=2.20 x 10(-3) to 2.6 x 10(-11)) for the number of tests performed (APOA5, CETP, GCKR, and GALNT2). Interestingly, our strongest signal was obtained for triglycerides with the minor allele of rs964184 (P=2.6 x 10(-11)) in the APOA1/C3/A4/A5 gene cluster region that is significantly more common in Mexicans (27%) than in whites (12%). It is important to confirm whether known loci have a consistent effect across ethnic groups. We show replication of 5 Caucasian genome-wide association studies lipid associations in Mexicans. The remaining loci will require a comprehensive investigation to exclude or verify their significance in Mexicans. We also demonstrate that rs964184 has a large effect (odds ratio, 1.74) and is more frequent in the Mexican population, and thus it may contribute to the high predisposition to dyslipidemias in Mexicans.

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.

Dyslipidemia links obesity to early cerebral neurochemical alterations

PubMed Central

Haley, Andreana P.; Gonzales, Mitzi M.; Tarumi, Takashi; Tanaka, Hirofumi

2013-01-01

Objective To examine the role of hypertension, hyperglycemia and dyslipidemia in potentially accounting for obesity-related brain vulnerability in the form of altered cerebral neurochemistry. Design and Methods Sixty-four adults, ages 40 to 60 years, underwent a health screen and proton magnetic resonance spectroscopy (1H MRS) of occipitoparietal grey matter to measure N-acetyl aspartate (NAA), choline (Cho), myo-inositol (mI) and glutamate (Glu) relative to creatine (Cr). The causal steps approach and non-parametric bootstrapping were utilized to assess if fasting glucose, mean arterial pressure or peripheral lipid/lipoprotein levels mediate the relationship between body mass index (BMI) and cerebral neurochemistry. Results Higher BMI was significantly related to higher mI/Cr, independent of age and sex. BMI was also significantly related to two of the proposed mediators, triglyceride and HDL-cholesterol, which were also independently related to increased mI/Cr. Finally, the relationship between BMI and mI/Cr, was significantly attenuated after inclusion of triglyceride and HDL-cholesterol into the model, one at a time, indicating statistical mediation. Conclusions Higher triglyceride and lower HDL levels statistically account for the association between BMI and myo-inositol, pointing towards a potentially critical role for dyslipidemia in the development of cerebral neurochemical alterations in obesity. PMID:23512296

Effect of Dietary Ethanolic Extract of Lavandula officinalis on Serum Lipids Profile in Rats

PubMed Central

Rabiei, Zahra; Rafieian-Kopaei, Mahmoud; Mokhtari, Shiva; Shahrani, Mehrdad

2014-01-01

Antioxidants are effective in prevention and treatment of cardiovascular diseases. Lavandula officinalis possesses antioxidant activity, therefore, in this study; the effects of Lavandula officinalis extract were investigated on serum lipids levels of rats. Experimental mature male Wistar rats were treated with 100, 200 or 400 mg/Kg/day of lavender ethanolic extract or distilled water for 25 days via gastric gavage (n=8 each group). At the end of 25th day, the serum cholesterol, triglyceride, HDL, LDL and VLDL levels, as well as atherogenic indices were determined in rats’ serum. The ethanolic extract of lavender decreased serum cholesterol, triglyceride, LDL and VLDL levels in 100 mg/Kg group (p=0.03, p=0.001, p=0.001, p=0.001, respectively). Serum HDL level increased in 100 mg/Kg/day group (p=0.01). Lavender extract decreased LDL/HDL level at doses of 100 and 200 mg/Kg/day (p=0.001, p=0.001, respectively). The TG/HDL levels decreased in experimental groups with doses of 100 and 200 mg/Kg/day (p=0.001, p=0.001, respectively). Lavandula officinalis extract exerts hypolipidemic effect in rats and might be beneficial in hyperlipidemic patients. PMID:25587318

Maternal dietary free or bound fructose diversely influence developmental programming of lipogenesis.

PubMed

Yuruk, Armagan Aytug; Nergiz-Unal, Reyhan

2017-12-01

Maternal dietary choices throughout preconception, pregnancy, and lactation irreversibly affect the development of fetal tissues and organs, known as fetal programming. Recommendations tend to emphasize reducing added sugars. However, the impact of maternal dietary free or bound fructose in added sugars on developmental programming of lipogenesis is unknown. Virgin Sprague-Dawley rats were randomly divided into five groups. Rats were given feed and plain water (control) or water containing maltodextrin (vehicle), fructose, high-fructose corn syrup (HFCS) containing 55% fructose, sucrose (20% w/v) for 12 weeks before mating and throughout the pregnancy and lactation periods. Body weight, water, and feed intake were measured throughout the study. At the end of the lactation period, blood was drawn to determine the fasting levels of glucose, insulin, triglycerides, and non-esterified fatty acids (NEFA) in blood. Triglycerides and acetyl Co-A Carboxylase-1 (ACC1) levels in livers were analyzed, and insulin resistance was calculated. The energy intake of dams in the HFCS group was higher than in the fructose group, while weight gain was less in the HFCS group than in the fructose group. HFCS resulted in greater insulin resistance in dams, whereas free fructose had a robust effect on the fetal programming of insulin resistance. Free fructose and HFCS in the maternal diet increased blood and liver triglycerides and NEFA content in pups. Furthermore, fructose and HFCS exposure increased phosphorylated ACC1 as compared to maltodextrin and control, indicating greater fatty acid synthesis in pups and dams. Different types of added sugar in the maternal diet have different metabolic effects on the developmental programming of lipogenesis. Consequently, high fructose intake via processed foods may increase the risk for chronic diseases, and free fructose might contribute to developmental programming of chronic diseases more than bound fructose.

Insulin resistance in obese children and adolescents.

PubMed

Romualdo, Monica Cristina dos Santos; Nóbrega, Fernando José de; Escrivão, Maria Arlete Meil Schimith

2014-01-01

To evaluate the presence of insulin resistance and its association with other metabolic abnormalities in obese children and adolescents. Retrospective study of 220 children and adolescents aged 5-14 years. Anthropometric measurements were performed (weight, height, and waist circumference) and clinical (gender, age, pubertal stage, and degree of obesity) and biochemical (glucose, insulin, total cholesterol, and fractions, triglycerides) data were analyzed. Insulin resistance was identified by the homeostasis model assessment for insulin resistance (HOMA-IR) index. The analysis of the differences between the variables of interest and the HOMA-IR quartiles was performed by ANOVA or Kruskal-Wallis tests. Insulin resistance was diagnosed in 33.20% of the sample. It was associated with low levels of high-density lipoprotein cholesterol (HDL-C; p=0.044), waist circumference measurement (p=0.030), and the set of clinical and metabolic (p=0.000) alterations. Insulin-resistant individuals had higher mean age (p=0.000), body mass index (BMI; p=0.000), abdominal circumference (p=0.000), median triglycerides (p=0.001), total cholesterol (p≤0.042), and low-density lipoprotein cholesterol (LDL-C; p≤0.027); and lower HDL-C levels (p=0.005). There was an increase in mean BMI (p=0.000), abdominal circumference (p=0.000), and median triglycerides (p=0.002) as the values of HOMA -IR increased, with the exception of HDL-C, which decreased (p=0.001). Those with the highest number of simultaneous alterations were between the second and third quartiles of the HOMA-IR index (p=0.000). The results confirmed that insulin resistance is present in many obese children and adolescents, and that this condition is associated with alterations that represent an increased risk for developing metabolic disorders in adulthood. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Metabolic fate of glucose and candidate signaling and excess-fuel detoxification pathways in pancreatic β-cells

PubMed Central

Mugabo, Yves; Zhao, Shangang; Lamontagne, Julien; Al-Mass, Anfal; Peyot, Marie-Line; Corkey, Barbara E.; Joly, Erik; Madiraju, S. R. Murthy; Prentki, Marc

2017-01-01

Glucose metabolism promotes insulin secretion in β-cells via metabolic coupling factors that are incompletely defined. Moreover, chronically elevated glucose causes β-cell dysfunction, but little is known about how cells handle excess fuels to avoid toxicity. Here we sought to determine which among the candidate pathways and coupling factors best correlates with glucose-stimulated insulin secretion (GSIS), define the fate of glucose in the β-cell, and identify pathways possibly involved in excess-fuel detoxification. We exposed isolated rat islets for 1 h to increasing glucose concentrations and measured various pathways and metabolites. Glucose oxidation, oxygen consumption, and ATP production correlated well with GSIS and saturated at 16 mm glucose. However, glucose utilization, glycerol release, triglyceride and glycogen contents, free fatty acid (FFA) content and release, and cholesterol and cholesterol esters increased linearly up to 25 mm glucose. Besides being oxidized, glucose was mainly metabolized via glycerol production and release and lipid synthesis (particularly FFA, triglycerides, and cholesterol), whereas glycogen production was comparatively low. Using targeted metabolomics in INS-1(832/13) cells, we found that several metabolites correlated well with GSIS, in particular some Krebs cycle intermediates, malonyl-CoA, and lower ADP levels. Glucose dose-dependently increased the dihydroxyacetone phosphate/glycerol 3-phosphate ratio in INS-1(832/13) cells, indicating a more oxidized state of NAD in the cytosol upon glucose stimulation. Overall, the data support a role for accelerated oxidative mitochondrial metabolism, anaplerosis, and malonyl-CoA/lipid signaling in β-cell metabolic signaling and suggest that a decrease in ADP levels is important in GSIS. The results also suggest that excess-fuel detoxification pathways in β-cells possibly comprise glycerol and FFA formation and release extracellularly and the diversion of glucose carbons to triglycerides and cholesterol esters. PMID:28280244

Association between carotid intima-media thickness and fasting blood glucose level: A population-based cross-sectional study among low-income adults in rural China.

PubMed

Gao, Liu; Bai, Lingling; Shi, Min; Ni, Jingxian; Lu, Hongyan; Wu, Yanan; Tu, Jun; Ning, Xianjia; Wang, Jinghua; Li, Yukun

2017-11-01

Carotid intima-media thickness (CIMT) is an established predictor of cardiovascular disease and stroke. We aimed to identify the association between CIMT and blood glucose, as well as the risk factors associated with increased CIMT in a low-income Chinese population. Stroke-free and cardiovascular disease-free residents aged ≥45 years were recruited. B-mode ultrasonography was carried out to measure CIMT. There were 2,643 participants (71.0%) in the normal group, 549 (14.7%) in the impaired fasting glucose group and 533 (14.3%) in the diabetes mellitus group. The determinants of increased CIMT were older age; male sex; low education; hypertension; smoking; high levels of systolic blood pressure, fasting blood glucose and low-density lipoprotein cholesterol; and low levels of diastolic blood pressure, triglycerides and high-density lipoprotein cholesterol, after adjusting for covariates. Age and hypertension were the common risk factors for increased CIMT in all three groups. Furthermore, male sex, smoking and high low-density lipoprotein cholesterol level were positively associated with the mean CIMT in the normal group; high triglycerides levels were negatively associated with the mean CIMT in the impaired fasting glucose group; and alcohol consumption was an independent risk factor for mean CIMT in the diabetes mellitus group. Hypertension was the greatest risk factor for increased CIMT. These findings suggest that it is crucial to manage and control traditional risk factors in low-income populations in China in order to decelerate the recent dramatic increase in stroke incidence, and to reduce the burden of stroke. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Antiobesity and Hypoglycaemic Effects of Aqueous Extract of Ibervillea sonorae in Mice Fed a High-Fat Diet with Fructose

PubMed Central

Rivera-Ramírez, Fabiola; Escalona-Cardoso, Gerardo N.; Garduño-Siciliano, Leticia; Galaviz-Hernández, Carlos; Paniagua-Castro, Norma

2011-01-01

Obesity, type II diabetes, and hyperlipidaemia, which frequently coexist and are strongly associated with oxidative stress, increase the risk of cardiovascular disease. An increase in carbohydrate intake, especially of fructose, and a high-fat diet are both factors that contribute to the development of these metabolic disorders. In recent studies carried out in diabetic rats, authors reported that Ibervillea sonorae had hypoglycaemic activity; saponins and monoglycerides present in the plant could be responsible for the effects observed. In the present study, we determined the effects of an aqueous I. sonorae extract on a murine model of obesity and hyperglycaemia, induced by a high-calorie diet, and the relationship of these effects with hepatic oxidation. A high-fat diet over a period of 8 weeks induced weight gain in the mice and increased triglycerides and blood glucose levels. Simultaneous treatment with I. sonorae aqueous extracts, at doses of 100, 200, and 400 mg/kg, decreased triglycerides and glycaemia levels, prevented an increase in body weight in a dose-dependent manner, and decreased hepatic lipid oxidation at a dose of 200 mg/kg. These data suggest that the aqueous extract from I. sonorae root prevents obesity, dyslipidaemia, and hyperglycaemia induced by a hypercaloric diet; however, high doses may induce toxicity. PMID:22174560

Antiobesity and hypoglycaemic effects of aqueous extract of Ibervillea sonorae in mice fed a high-fat diet with fructose.

PubMed

Rivera-Ramírez, Fabiola; Escalona-Cardoso, Gerardo N; Garduño-Siciliano, Leticia; Galaviz-Hernández, Carlos; Paniagua-Castro, Norma

2011-01-01

Obesity, type II diabetes, and hyperlipidaemia, which frequently coexist and are strongly associated with oxidative stress, increase the risk of cardiovascular disease. An increase in carbohydrate intake, especially of fructose, and a high-fat diet are both factors that contribute to the development of these metabolic disorders. In recent studies carried out in diabetic rats, authors reported that Ibervillea sonorae had hypoglycaemic activity; saponins and monoglycerides present in the plant could be responsible for the effects observed. In the present study, we determined the effects of an aqueous I. sonorae extract on a murine model of obesity and hyperglycaemia, induced by a high-calorie diet, and the relationship of these effects with hepatic oxidation. A high-fat diet over a period of 8 weeks induced weight gain in the mice and increased triglycerides and blood glucose levels. Simultaneous treatment with I. sonorae aqueous extracts, at doses of 100, 200, and 400 mg/kg, decreased triglycerides and glycaemia levels, prevented an increase in body weight in a dose-dependent manner, and decreased hepatic lipid oxidation at a dose of 200 mg/kg. These data suggest that the aqueous extract from I. sonorae root prevents obesity, dyslipidaemia, and hyperglycaemia induced by a hypercaloric diet; however, high doses may induce toxicity.

Low nonfasting triglycerides and reduced all-cause mortality: a mendelian randomization study.

PubMed

Thomsen, Mette; Varbo, Anette; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

2014-05-01

Increased nonfasting plasma triglycerides marking increased amounts of cholesterol in remnant lipoproteins are important risk factors for cardiovascular disease, but whether lifelong reduced concentrations of triglycerides on a genetic basis ultimately lead to reduced all-cause mortality is unknown. We tested this hypothesis. Using individuals from the Copenhagen City Heart Study in a mendelian randomization design, we first tested whether low concentrations of nonfasting triglycerides were associated with reduced all-cause mortality in observational analyses (n = 13 957); second, whether genetic variants in the triglyceride-degrading enzyme lipoprotein lipase, resulting in reduced nonfasting triglycerides and remnant cholesterol, were associated with reduced all-cause mortality (n = 10 208). During a median 24 and 17 years of 100% complete follow-up, 9991 and 4005 individuals died in observational and genetic analyses, respectively. In observational analyses compared to individuals with nonfasting plasma triglycerides of 266-442 mg/dL (3.00-4.99 mmol/L), multivariably adjusted hazard ratios for all-cause mortality were 0.89 (95% CI 0.78-1.02) for 177-265 mg/dL (2.00-2.99 mmol/L), 0.74 (0.65-0.84) for 89-176 mg/dL (1.00-1.99 mmol/L), and 0.59 (0.51-0.68) for individuals with nonfasting triglycerides <89 mg/dL (<1.00 mmol/L). The odds ratio for a genetically derived 89-mg/dL (1-mmol/L) lower concentration in nonfasting triglycerides was 0.50 (0.30-0.82), with a corresponding observational hazard ratio of 0.87 (0.85-0.89). Also, the odds ratio for a genetically derived 50% lower concentration in nonfasting triglycerides was 0.43 (0.23-0.80), with a corresponding observational hazard ratio of 0.73 (0.70-0.77). Genetically reduced concentrations of nonfasting plasma triglycerides are associated with reduced all-cause mortality, likely through reduced amounts of cholesterol in remnant lipoproteins.

Relation with HOMA-IR and thyroid hormones in obese Turkish women with metabolic syndrome.

PubMed

Topsakal, S; Yerlikaya, E; Akin, F; Kaptanoglu, B; Erürker, T

2012-03-01

The aim of this study was to investigate the relationship between insulin resistance and thyroid function in obese pre- and postmenopausal women with or without metabolic syndrome (MetS). 141 obese women were divided into two groups, HOMA-IR<2.7 and HOMA-IR>2.7, to evaluate relation with HOMA-IR and fatness, hormone and blood parameters. They were then divided into four groups as pre- and postmenopausal with or without MetS. Various fatness, hormone and blood parameters were examined. Statistically significant difference was found in weight, body mass index (BMI), waist circumference, fat%, fasting insulin, TSH, FT3, FT4, FSH, Anti-microsomal antibody (ANTIM) and triglycerides levels in HOMA-IR<2.7 and HOMA-IR>2.7 obese Turkish women. This study showed that age, weight, BMI, waist circumference, fat%, fasting insulin, FT3, ANTIM, FSH, LH, total cholesterol, triglycerides, HDL, HOMA-IR, systolic and diastolic blood pressure levels were related in preand post menopausal status in obese women with or without MetS. Obesity may influence the levels of thyroid hormones and increases the risk of MetS in women. Postmenopausal status with MetS is associated with an increased TSH, FT3 and FT4 levels and HOMA-IR in obese women. Strong relation was observed with MetS and TSH and FT3 levels.

Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies.

PubMed

Bays, Harold E; Ballantyne, Christie M; Doyle, Ralph T; Juliano, Rebecca A; Philip, Sephy

2016-09-01

Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis.

PubMed

Allen, Robert W; Schwartzman, Emmanuelle; Baker, William L; Coleman, Craig I; Phung, Olivia J

2013-01-01

Cinnamon has been studied in randomized controlled trials (RCTs) for its glycemic-lowering effects, but studies have been small and show conflicting results. A prior meta-analysis did not show significant results, but several RCTs have been published since then. We conducted an updated systematic review and meta-analysis of RCTs evaluating cinnamon's effect on glycemia and lipid levels. MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched through February 2012. Included RCTs evaluated cinnamon compared with control in patients with type 2 diabetes and reported at least one of the following: glycated hemoglobin (A1c), fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or triglycerides. Weighted mean differences (with 95% confidence intervals) for endpoints were calculated using random-effects models. In a meta-analysis of 10 RCTs (n = 543 patients), cinnamon doses of 120 mg/d to 6 g/d for 4 to 18 weeks reduced levels of fasting plasma glucose (-24.59 mg/dL; 95% CI, -40.52 to -8.67 mg/dL), total cholesterol (-15.60 mg/dL; 95% CI, -29.76 to -1.44 mg/dL), LDL-C (-9.42 mg/dL; 95% CI, -17.21 to -1.63 mg/dL), and triglycerides (-29.59 mg/dL; 95% CI, -48.27 to -10.91 mg/dL). Cinnamon also increased levels of HDL-C (1.66 mg/dL; 95% CI, 1.09 to 2.24 mg/dL). No significant effect on hemoglobin A1c levels (-0.16%; 95%, CI -0.39% to 0.02%) was seen. High degrees of heterogeneity were present for all analyses except HDL-C (I(2) ranging from 66.5% to 94.72%). The consumption of cinnamon is associated with a statistically significant decrease in levels of fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, and an increase in HDL-C levels; however, no significant effect on hemoglobin A1c was found. The high degree of heterogeneity may limit the ability to apply these results to patient care, because the preferred dose and duration of therapy are unclear.

Effects of climatic factors on plasma lipid levels: A 5-year longitudinal study in a large Chinese population.

PubMed

Zhou, Xiaoming; Lin, Haiyan; Zhang, Shigang; Ren, Jianwei; Wang, Zhe; Zhang, Yun; Wang, Mansen; Zhang, Qunye

2016-01-01

The rules and mechanisms of seasonal changes in plasma lipid levels, which may be related to annual rhythmicity of incidence and mortality of cardiovascular diseases, are still controversial. The objectives of this study were to study the effects of climatic factors on plasma lipid levels and to preliminarily reveal mechanisms of annual rhythmicity of plasma lipid levels. A longitudinal study was performed using health examination data of 5 consecutive years (47,270 subjects) in Jinan, China. The climate in Jinan is typical temperate continental monsoon climate with huge temperature difference between winter and summer (>30°C). After considering and adjusting those classical lipid-associated risk factors, such as age, gender, diet, exercise, blood pressure, body weight, change of body weight, body mass index, glycemia, alanine aminotransferase, and creatinine, only air temperature could still significantly affect plasma lipid levels among the main climatic factors (humidity, precipitation, and so forth). For men, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was decreased significantly 0.35, 0.18, and 0.06 mmol/L, respectively, whereas triglyceride was increased significantly 0.12 mmol/L for every 10°C increase in air temperature. For women, total cholesterol and high-density lipoprotein cholesterol were decreased notably 0.73 and 0.32 mmol/L, and low-density lipoprotein cholesterol was increased significantly 0.26 mmol/L for every 10°C increase in air temperature, whereas triglyceride was not significantly affected by air temperature. Air temperature is an independent risk factor for plasma lipid levels besides those classical lipid-associated risk factors. The annual air temperature fluctuations might be an important mechanism of the seasonal changes of lipids. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Identification of lipidomic markers of chronic 3,3',4,4',5-pentachlorobiphenyl (PCB 126) exposure in the male rat liver.

PubMed

Kania-Korwel, Izabela; Wu, Xianai; Wang, Kai; Lehmler, Hans-Joachim

2017-09-01

Exposure to PCB 126, an environmentally relevant aryl hydrocarbon receptor agonist, is an environmental factor causing hepatic steatosis in rodent models; however, the lipidome of PCB 126-exposed rats has not been investigated in-depth. The objective of the present study was therefore to characterize dose-dependent changes in the lipid profile in the liver of male Sprague-Dawley rats exposed to PCB 126. Rats were exposed for three month to intraperitoneal injections of 0.01, 0.05 and 0.2μmol/kg bw PCB 126 in corn oil. Control animals were exposed in parallel and received corn oil alone. Lipids were extracted from whole liver homogenate and levels of polar lipids and fatty acids incorporated into triglycerides (FA TAGs ) were determined with tandem mass spectrometry using electrospray ionization. PCB 126 exposure increased the hepatic content of polar lipids and FA TAGs . Protein adjusted levels of several polar lipid classes, in particular phosphatidylserine levels, decreased, whereas FA TAGs levels typically increased with increasing PCB 126 dose. Sensitive, dose-dependent endpoints of PCB 126 exposure included an increase in levels of adrenic acid incorporated into triglycerides and changes in levels of certain ether-linked phospholipid and 1-alkyl/1-alkenyldiacylglycerol species, as determined using partial least square discriminant analysis (PLS-DA) and ANOVA. These changes in the composition of polar lipids and fatty acid in the liver of PCB 126 exposed rats identified several novel markers of PCB 126-mediated fatty liver disease that need to be validated in further studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary oxidized linoleic acid lowers triglycerides via APOA5/APOClll dependent mechanisms

PubMed Central

Garelnabi, Mahdi; Selvarajan, Krithika; Litvinov, Dmitry; Santanam, Nalini; Parthasarathy, Sampath

2008-01-01

Previously we have shown that intestinal cells efficiently take up oxidized fatty acids (OxFAs) and that atherosclerosis is increased when animals are fed a high cholesterol diet in the presence of oxidized linoleic acid. Interestingly, we found that in the absence of dietary cholesterol, the oxidized fatty acid fed low-density lipoprotein (LDL) receptor negative mice appeared to have lower plasma triglyceride (TG) levels as compared to animals fed oleic acid. In the present study, we fed C57BL6 mice a normal mice diet supplemented with oleic acid or oxidized linoleic acid (at 18 mg/animal/day) for 2 weeks. After the mice were sacrificed, we measured the plasma lipids and collected livers for the isolation of RNA. The results showed that while there were no significant changes in the levels of total cholesterol and high-density lipoprotein cholesterol (HDLc), there was a significant decrease (41.14%) in the levels of plasma TG in the mice that were fed oxidized fatty acids. The decreases in plasma TG levels were accompanied by significant increases (P < 0.001) in the expressions of APOA5 and acetyl-CoA oxidase genes as well as a significant (P < 0.04) decrease in APOClll gene expression. Oxidized lipids have been suggested to be ligands for peroxisome proliferator-activated receptor (PPARα). However, there were no increases in the mRNA or protein levels of PPARα in the oxidized linoleic acid fed animals. These results suggest that oxidized fatty acids may act through an APOA5/APOClll mechanism that contributes to lowering of TG levels other than PPARα induction. PMID:18243209

Metabolic effects of dietary sugar beet pulp or wheat bran in growing female pigs.

PubMed

Weber, T E; Kerr, B J

2012-02-01

An experiment was conducted to determine the effects of feeding a moderate level of 2 different fiber sources on energy metabolites; mitochondrial biogenesis in the intestine, liver, and muscle; and the expression of some genes that regulate energy metabolism in intestine, liver, muscle, and adipose tissue. Female pigs (n = 36; BW = 15.0 ± 0.7 kg) were fed diets containing no added fiber, 12.5% sugar beet pulp (SBP), or 12.5% wheat bran (WB) for 24 d. Blood samples were collected on d 7 and 24 for cholesterol, glucose, NEFA, and triglyceride analyses. At completion of the experiment, ileum, colon, subcutaneous adipose, and LM samples were obtained from a subset (n = 6) of pigs fed each diet for analysis of tissue mitochondrial DNA (mtDNA) content and mRNA abundance by quantitative real-time reverse-transcription PCR. Glycogen and triglyceride content of liver and LM were determined, and colon content VFA was also determined. The addition of SBP or WB to the diet had no effect (P > 0.55) on ADG, ADFI, or G:F. Serum NEFA and triglycerides were increased (P < 0.05) in pigs fed SBP compared with pigs fed the control diet or WB on d 7, and NEFA remained increased (P < 0.05) on d 24 in pigs fed SBP. Dietary fiber had no effect (P > 0.24) on glycogen and triglyceride content of liver or LM, but colonic acetate concentrations were increased (P < 0.05) in pigs fed either SBP or WB. Pigs fed WB had an increased (P < 0.05) mtDNA content in ileum tissue and increased (P < 0.05) citrate synthase mRNA in colon tissue. In the liver, feeding either SBP or WB led to a decrease (P < 0.05) in mtDNA content, whereas feeding WB decreased (P < 0.05) mtDNA abundance in the LM, and feeding either SBP or WB decreased (P < 0.05) expression of citrate synthase mRNA. Quantitative reverse-transcription PCR revealed that feeding WB increased (P < 0.05) proliferating cell nuclear antigen mRNA abundance in the ileum and colon. Feeding WB increased (P < 0.05) mRNA abundance of a regulator of mitochondrial biogenesis, PPAR coactivator 1 α, in ileum tissue, and increased (P < 0.05) mRNA abundance of another mediator of mitochondrial biogensis, sirtuin 1, in colon tissue. Colonic mRNA expression of fasting-induced adipose factor was increased (P < 0.05) in pigs fed either SBP or WB, and adipose triglyceride lipase mRNA abundance was increased (P < 0.05) in adipose tissue of pigs fed SBP. These data indicate that increasing dietary fiber can increase the capacity of the intestine for oxidative metabolism and induce a repartitioning of energy metabolites depending on fiber source.

Changes in selected serum parameters of broiler chicken fed supplemental chromium.

PubMed

Króliczewska, B; Zawadzki, W; Dobrzanski, Z; Kaczmarek-Oliwa, A

2004-12-01

The present study was conducted to evaluate the effect of chromium (Cr) from Cr yeast on the growth performance and total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, total protein and Cr concentration in the serum of broiler chicken. The birds were fed a control diet or a control diet supplemented with Cr at a level of 300, 500 microg/kg Cr. The supplementation of 500 mug/kg Cr increased body weight, weight gain and feed efficiency (p < 0.05). In addition, supplementation with Cr decreased the serum total cholesterol, LDL cholesterol (p < 0.05), triglycerides (p < 0.05) and glucose (p < 0.05) concentrations whereas serum HDL cholesterol increased. Serum total protein and serum Cr concentration slightly but not significantly increased in both Cr groups. The study suggest that Cr supplementation particularly at 500 microg/kg Cr from Cr yeast can influence on carbohydrate and lipid metabolism of broiler chicken and can be used as additives in animal diet but it still needs more investigations.

Fructose impairs glucose-induced hepatic triglyceride synthesis

PubMed Central

2011-01-01

Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases. PMID:21261970

Triglyceride Treatment in the Age of Cholesterol Reduction

PubMed Central

Agrawal, Nidhi; Corradi, Patricia Freitas; Gumaste, Namrata; Goldberg, Ira J.

2017-01-01

Cholesterol reduction has markedly reduced major cardiovascular disease (CVD) events and shown regression of atherosclerosis in some studies. However, CVD has for decades also been associated with increased levels of circulating triglyceride (TG)-rich lipoproteins. Whether this is due to a direct toxic effect of these lipoproteins on arteries or whether this is merely an association is unresolved. More recent genetic analyses have linked genes that modulate TG metabolism with CVD. Moreover, analyses of subgroups of hypertriglyceridemic (HTG) subjects in clinical trials using fibric acid drugs have been interpreted as evidence that TG reduction reduces CVD events. This review will focus on how HTG might cause CVD, whether TG reduction makes a difference, what pathophysiological defects cause HTG, and what options are available for treatment. PMID:27544319

Daily Physical Activity Assessed by a Triaxial Accelerometer Is Beneficially Associated with Waist Circumference, Serum Triglycerides, and Insulin Resistance in Japanese Patients with Prediabetes or Untreated Early Type 2 Diabetes.

PubMed

Hamasaki, Hidetaka; Noda, Mitsuhiko; Moriyama, Sumie; Yoshikawa, Reo; Katsuyama, Hisayuki; Sako, Akahito; Mishima, Shuichi; Kakei, Masafumi; Ezaki, Osamu; Yanai, Hidekatsu

2015-01-01

To investigate the association between daily physical activity and metabolic risk factors in Japanese adults with prediabetes or untreated early type 2 diabetes (T2D). Daily physical activity level was measured using a triaxial accelerometer. We assessed correlations between physical activity level and waist circumference, blood pressure, fasting levels of plasma glucose, serum triglycerides, and insulin and homeostasis model assessment-insulin resistance (HOMA-IR). A total of 80 patients were studied. After adjustment for age and body mass index, in all subjects, physical activity level was negatively associated with waist circumference (β = -0.124, P = 0.018) and fasting serum triglycerides (β = -0.239, P = 0.035), insulin (β = -0.224, P = 0.022). In men, physical activity level was negatively associated with systolic blood pressure (β = -0.351, P = 0.044), fasting plasma glucose (β = -0.369, P = 0.025) and insulin (β = -0.362, P = 0.012), and HOMA-IR (β = -0.371, P = 0.011). No significant associations were found between physical activity level and metabolic risk factors in women. Objectively measured daily physical activity is beneficially associated with waist circumference, serum triglycerides, and insulin resistance in individuals with prediabetes or untreated early T2D. (This trial is registered with UMIN000015774.).

Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

PubMed

Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

2012-01-01

A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels <2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dL) off all medications were as follows: total cholesterol 222, triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease. Copyright © 2012. Published by Elsevier Inc.

Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

PubMed Central

Vega, Claudia C; Reyes-Castro, Luis A; Bautista, Claudia J; Larrea, Fernando; Nathanielsz, Peter W; Zambrano, Elena

2013-01-01

BACKGROUND Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO. HYPOTHESIS MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes. METHODS F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed. RESULTS Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise. CONCLUSIONS MEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status. PMID:23949616

Cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians: A cross sectional study

PubMed Central

Guptha, Soneil; Gupta, Rajeev; Deedwania, Prakash; Bhansali, Anil; Maheshwari, Anuj; Gupta, Arvind; Gupta, Balkishan; Saboo, Banshi; Singh, Jitendra; Achari, Vijay; Sharma, Krishna Kumar

2014-01-01

Objective To determine levels of cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians. Methods Population based 6123 subjects (men 3388) were evaluated. Mean±1SD of various cholesterol lipoproteins (total, HDL, LDL and non-HDL cholesterol) and triglycerides were reported. Subjects were classified according to US National Cholesterol Education Program. Results Age-adjusted levels in men and women were cholesterol total 178.4 ± 39 and 184.6 ± 39, HDL 44.9 ± 11 and 51.1 ± 11, LDL 102.5 ± 33 and 106.2 ± 33, total:HDL 4.15 ± 1.2 and 3.79 ± 1.0 and triglycerides 162.5 ± 83 and 143.7 ± 83 mg/dl. Age-adjusted prevalence (%) in men and women, respectively were, total cholesterol ≥200 mg/dl 25.1 and 24.9, LDL cholesterol ≥130 mg/dl 16.3 and 15.1 and ≥100 mg/dl 49.5 and 49.7, HDL cholesterol <40/<50 mg/dl 33.6 and 52.8, total:HDL cholesterol ≥4.5 29.4 and 16.8, and triglycerides ≥150 mg/dl 42.1 and 32.9%. Cholesterol level was significantly greater in subjects with better socioeconomic status, body mass index and waist circumference while triglycerides were more among those with high socioeconomic status, fat intake, body mass index and waist circumference (p < 0.05). Hypercholesterolemia awareness (15.6%), treatment (7.2%) and control (4.1%) were low. Conclusions Mean cholesterol and LDL cholesterol are low and triglycerides were high in urban Asian Indians. Most prevalent dyslipidemias are borderline high LDL, low HDL and high triglycerides. Subjects with high socioeconomic status, high fat intake and greater adiposity have higher total and LDL cholesterol and triglyceride and lower HDL cholesterol. PMID:24973832

The impact of carvedilol and metoprolol on serum lipid concentrations and symptoms in patients with hyperthyroidism.

PubMed

Ozbilen, Sabahattin; Eren, Mehmet Ali; Turan, Mehmet Nuri; Sabuncu, Tevfik

2012-01-01

Hyperthyroidism is associated with unpleasant symptoms and hypertension due to increased adrenergic tone. Therefore, beta-blockers are often used in hyperthyroid patients. While some beta-blockers (such as propronolol and metoprolol) may have unwanted effects on lipid profile, carvedilol, a new alpha- and beta-blocker, has been suggested to have some metabolic advantages with respect to lipid profiles in hypertensive patients. However, this has not been shown in hyperthyroid patients. We aimed to compare the effects of two beta-blockers (metoprolol and carvedilol) on the lipid profiles of hyperthyroid patients with hypertension. Thirty patients with hyperthyroidism and hypertension were randomly assigned to receive either carvedilol (n = 15) or metoprolol (n = 15). Thyroid-stimulating hormone (TSH), free T3, free T4, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and total cholesterol levels were measured before and following 3 months of treatment. Systolic and diastolic blood pressure, heart rate, TSH, and free T4 improved significantly in both treatment groups. There were no statistically significant changes in the lipid parameters in either of the two treatment groups; however, triglyceride levels slightly decreased with carvedilol treatment. There were also no differences between the two groups in terms of the typical symptoms of hyperthyroidism. Carvedilol might be a preferred agent to treat hyperthyroid patients who have hypertension and dyslipidemia. This is likely due to the possible beneficial effect of carvedilol on lipid parameters, especially on triglyceride levels.

Lipid regulation in lipodystrophy versus the obesity-associated metabolic syndrome: the dissociation of HDL-C and triglycerides.

PubMed

Joseph, Jalaja; Shamburek, Robert D; Cochran, Elaine K; Gorden, Phillip; Brown, Rebecca J

2014-09-01

There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%). Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome. This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy. Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy. Serum triglycerides and HDL-C were measured. At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C. The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.

Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery.

PubMed

Verras, Christos G; Christou, Georgios A; Simos, Yannis V; Ayiomamitis, George D; Melidonis, Andreas J; Kiortsis, Dimitrios N

2017-07-01

The elucidation of the changes of fetuin-A in the context of bariatric surgery. Twenty obese patients (8 males, 12 females; body mass index = 42.5±3.4 kg/m2) were studied at baseline and 6 months after bariatric surgery. Serum fetuin-A levels did not differ with regard to the presence of each individual component of the Metabolic Syndrome (MetS) at baseline, except for hypertriglyceridaemia [increased serum fetuin-A levels (p=0.011)]. Circulating fetuin-A was positively correlated with serum triglycerides (TG) (r=0.461, p=0.047) and negatively correlated with serum globulins (r=-0.477, p=0.033) and C-reactive protein (CRP) (r=-0.604, p=0.010), while it independently predicted TG at baseline. Circulating fetuin-A did not change during the 6 months either in the whole population or in the subgroups of patients who were positive for each individual component of MetS at baseline and negative for this component at 6 months of follow-up, except for hypertriglyceridaemia [reduction of serum fetuin-A levels (p=0.046)]. The subgroup of patients with a decrease in circulating fetuin-A during the 6 months was characterized by a smaller reduction of serum globulins (p=0.003) and CRP (p=0.049). The change in serum fetuin-A levels over the 6 months was positively correlated with the change in TG (r=0.592, p=0.006) and negatively correlated with the change in serum globulins (r=-0.523, p=0.018) and CRP (r=-.494, p=0.037). Circulating fetuin-A predicted serum triglycerides before as well as 6 months after bariatric surgery.

The antioxidant status of coenzyme Q10 and vitamin E in children with type 1 diabetes.

PubMed

Alkholy, Usama M; Abdalmonem, Nermin; Zaki, Ahmed; Elkoumi, Mohamed A; Hashim, Mustafa I Abu; Basset, Maha A A; Salah, Hossam E

2018-02-07

The purpose of this study was to evaluate the antioxidant status of plasma vitamin E and plasma and intracellular coenzyme Q10 in children with type 1 diabetes. This case-control study was conducted on 72 children with type 1 diabetes and compared to 48 healthy children, who were age, sex, and ethnicity-matched. The diabetic children were divided according to their glycosylated hemoglobin (A1c %) into two groups: poor and good glycemic control groups. All children underwent full history taking, clinical examination, and laboratory measurement of complete blood count, A1c %, plasma cholesterol, triglycerides, and vitamin E levels and coenzyme Q10 levels in plasma, erythrocytes, and platelets. Children with poor glycemic control showed significantly higher plasma vitamin E, coenzyme Q10, triglycerides, low-density lipoproteins, waist circumference/height ratio, cholesterol levels, and lower high-density lipoproteins and platelet coenzyme Q10 redox status in comparison to those with good glycemic control and the control group (p<0.05). Plasma coenzyme Q10 showed a positive correlation with the duration of type 1 diabetes, triglycerides, cholesterol, vitamin E, and A1c %, and negative correlation with the age of the diabetic group (p<0.05). The platelet redox status showed a negative correlation with the A1c % levels (r=-0.31; p=0.022) and the duration of type 1 diabetes (r=-0.35, p=0.012). Patients with type 1 diabetes, especially poorly controlled, had elevation of plasma vitamin E and coenzyme Q10 levels and decreased platelet redox status of coenzyme Q10, which may be an indicator of increased oxidative stress. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly.

PubMed

Choi, Hyo Jung; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Sohn, Bo Kyung; Baek, Hye Won; Lee, Jun Ho; Kim, Hyun Jung; Han, Ji Young; Yoon, Eun Jin; Kim, Yu Kyeong; Woo, Jong Inn; Lee, Dong Young

2016-08-01

Although many preclinical studies have suggested the possible linkage between dyslipidemia and cerebral amyloid deposition, the association between serum lipid measures and cerebral amyloid-beta (Aβ) deposition in human brain is still poorly known. We aimed to investigate the association in cognitively normal (CN) elderly individuals. Cross-sectional study. University hospital dementia clinic. 59 CN elderly. The study measures included comprehensive clinical and neuropsychological assessment based on the CERAD protocol, magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B positron emission tomography scans, and quantification for serum lipid biomarkers. Multiple linear regression analyses showed that a higher serum triglycerides level was associated with heavier global cerebral Aβ deposition even after controlling age, sex, and apolipoprotein E ε4 genotype. Serum apolipoprotein B also showed significant positive association with global cerebral Aβ deposition, but the significance disappeared after controlling serum triglycerides level. No association was found between other lipid measures and global cerebral Aβ deposition. The findings suggest that serum triglycerides are closely associated with cerebral amyloidosis, although population-based prospective studies are needed to provide further evidence of the causative effect of triglycerides on cerebral amyloidosis. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Serum lipid levels for a multicultural population in Auckland, New Zealand: results from the Diabetes Heart and Health Survey (DHAH) 2002-2003.

PubMed

Gentles, Dudley; Metcalf, Patricia; Dyall, Lorna; Scragg, Robert; Sundborn, Gerhard; Schaaf, David; Black, Peter N; Jackson, Rodney T

2007-11-09

To describe mean serum lipid concentrations for Maori, Pacific people (mostly of Samoan, Tongan, Niuean, or Cook Islands origin), and Others (mostly New Zealand-born Europeans), and to identify risk factors for an adverse lipid profile. A cross-sectional survey of adults aged between 35-74 years within the Auckland area. There were 1006 Maori, 996 Pacific people, and 2021 'Others' Fasting blood samples were collected from participants, and total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), and triglycerides were measured. Maori and Pacific people had similar mean serum total and LDL cholesterol levels but lower HDL levels and higher total to HDL cholesterol ratios compared to Others (adjusted for age and gender). Maori also had higher triglycerides than Others. High BMI and cigarette smoking were positively associated with unfavourable lipid profiles, while current alcohol drinking and vigorous leisure time activity were associated with increased HDL cholesterol and lower total to HDL cholesterol ratios. Over 90% of all ethnic groups had total cholesterol levels above currently accepted optimal levels (>4 mmol/L) and two-thirds were above 5 mmol/L. While 30% of Others had a total to HDL cholesterol ratio above the 'optimal' threshold of 4.5, 40% of Maori and 44% of pacific people were above this level. This is the first study to simultaneously assess lipid levels in Maori, Pacific people, and Others in one population-based study. Despite similar total and LDL cholesterol levels in all ethnic groups; overweight, obesity, and current cigarette smoking were the main risk factors for their adverse lipid profiles. Engaging in leisure-time activity and alcohol consumption (and not surprisingly lipid-lowering drugs) were associated with better lipid profiles. We confirm that the main lipid-related cardiovascular disease risk in Maori and Pacific people is due to their low HDL and high triglyceride levels.

Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.

PubMed

Tentolouris, N; Kolia, M; Tselepis, A D; Perea, D; Kitsou, E; Kyriaki, D; Tambaki, A P; Karabina, S P; Sala, C; Fragoulopoulos, E; Katsilambros, N

2003-09-01

The effect of acute repaglinide administration (2 mg) on postprandial glycaemia and lipaemia has been examined in 20 subjects with type 2 diabetes mellitus. Each subject received in the morning, after a 12 to 14 h fast, a standard mixed meal (total energy 783 kcal), preceded by one tablet of 2 mg repaglinide or placebo. Chylomicrons and chylomicron-deficient plasma were prepared by ultracentrifugation. Triglyceride levels in CM fraction (CM-triglycerides) in total plasma as well as in CM-deficient plasma (non-CM-triglycerides) were determined. A significant reduction in postprandial glycaemia was observed after repaglinide administration compared to placebo ( p < 0.001). Plasma concentrations of total triglycerides, CM-triglycerides, non-CM-triglycerides, free fatty acids and the other plasma lipids measured, were not significantly different between the two phases of the study. It is concluded that, in contrast to sulphonylureas, acute repaglinide administration does not improve postprandial lipaemia in patients with type 2 diabetes.

Prevalence of metabolic syndrome and associated cardiovascular risk factors in Guatemalan school children

PubMed Central

Mbowe, Omar; Diaz, Alicia; Wallace, Jana; Mazariegos, Manolo; Jolly, Pauline

2014-01-01

Objectives Guatemala is experiencing a nutritional and lifestyle transition. While chronic malnutrition is prevalent, overweight, obesity and chronic diseases have increased substantially in the country. This study was conducted to investigate the prevalence of metabolic syndrome and the associated cardiovascular risk factors in the pre-adolescent Guatemalan population. Methods A cross-sectional study was conducted among 302 Guatemalan children (8–13 years old) attending public and private schools in the Municipality of Chimaltenango. Demographic data and anthropometric and blood pressure measurements were collected. A blood sample was taken after an 8-hour overnight fast and analyzed for glucose, triglyceride and high-density lipoprotein cholesterol levels. The data were analyzed to identify factors associated with metabolic syndrome and with its components. Results The prevalence of metabolic syndrome in the study population was 2.0%. However, approximately 54% of the children had at least one component of metabolic syndrome, while none had four or five of the components. The three most prevalent risk factors were high triglycerides (43.4%), low HDL cholesterol (17.2%) and obesity (12.3%). Boys were more likely to be obese than girls and rural children were more likely to have higher triglyceride levels than urban children. Conclusions Although the prevalence of metabolic syndrome is low, the fact that majority of the children already have at least one component of metabolic syndrome is cause for concern since components of metabolic syndrome can continue into adulthood and increase the risk for chronic diseases later in life. Therefore, immediate action should be taken to address the problem. PMID:24337775

Prevalence of metabolic syndrome and associated cardiovascular risk factors in Guatemalan school children.

PubMed

Mbowe, Omar; Diaz, Alicia; Wallace, Jana; Mazariegos, Manolo; Jolly, Pauline

2014-09-01

Guatemala is experiencing a nutritional and lifestyle transition. While chronic malnutrition is prevalent, overweight, obesity and chronic diseases have increased substantially in the country. This study was conducted to investigate the prevalence of metabolic syndrome and the associated cardiovascular risk factors in the pre-adolescent Guatemalan population. A cross-sectional study was conducted among 302 Guatemalan children (8-13 years old) attending public and private schools in the Municipality of Chimaltenango. Demographic data and anthropometric and blood pressure measurements were collected. A blood sample was taken after an 8 h overnight fast and analyzed for glucose, triglyceride and high-density lipoprotein cholesterol levels. The data were analyzed to identify factors associated with metabolic syndrome and with its components. The prevalence of metabolic syndrome in the study population was 2.0 %. However, approximately 54 % of the children had at least one component of metabolic syndrome, while none had four or five of the components. The three most prevalent risk factors were high triglycerides (43.4 %), low HDL cholesterol (17.2 %) and obesity (12.3 %). Boys were more likely to be obese than girls and rural children were more likely to have higher triglyceride levels than urban children. Although the prevalence of metabolic syndrome is low, the fact that majority of the children already have at least one component of metabolic syndrome is cause for concern since components of metabolic syndrome can continue into adulthood and increase the risk for chronic diseases later in life. Therefore, immediate action should be taken to address the problem.

Lipid emulsions – Guidelines on Parenteral Nutrition, Chapter 6

PubMed Central

Adolph, M.; Heller, A. R.; Koch, T.; Koletzko, B.; Kreymann, K. G.; Krohn, K.; Pscheidl, E.; Senkal, M.

2009-01-01

The infusion of lipid emulsions allows a high energy supply, facilitates the prevention of high glucose infusion rates and is indispensable for the supply with essential fatty acids. The administration of lipid emulsions is recommended within ≤7 days after starting PN (parenteral nutrition) to avoid deficiency of essential fatty acids. Low-fat PN with a high glucose intake increases the risk of hyperglycaemia. In parenterally fed patients with a tendency to hyperglycaemia, an increase in the lipid-glucose ratio should be considered. In critically ill patients the glucose infusion should not exceed 50% of energy intake. The use of lipid emulsions with a low phospholipid/triglyceride ratio is recommended and should be provided with the usual PN to prevent depletion of essential fatty acids, lower the risk of hyperglycaemia, and prevent hepatic steatosis. Biologically active vitamin E (α-tocopherol) should continuously be administered along with lipid emulsions to reduce lipid peroxidation. Parenteral lipids should provide about 25–40% of the parenteral non-protein energy supply. In certain situations (i.e. critically ill, respiratory insufficiency) a lipid intake of up to 50 or 60% of non-protein energy may be reasonable. The recommended daily dose for parenteral lipids in adults is 0.7–1.3 g triglycerides/kg body weight. Serum triglyceride concentrations should be monitored regularly with dosage reduction at levels >400 mg/dl (>4.6 mmol/l) and interruption of lipid infusion at levels >1000 mg/dl (>11.4 mmol/l). There is little evidence at this time that the choice of different available lipid emulsions affects clinical endpoints. PMID:20049078

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.

Cranberry juice increases antioxidant status without affecting cholesterol homeostasis in orchidectomized rats.

PubMed

Deyhim, Farzad; Patil, Bhimanagouda S; Villarreal, Arnulfo; Lopez, Erica; Garcia, Kristi; Rios, Ryan; Garcia, Claudia; Gonzales, Cheri; Mandadi, Kranthi

2007-03-01

Oxidative stress and hypogonadism are linked to the increased incidence of cardiovascular disease in males. The objective of this research was to delineate whether drinking cranberry juice for 4 months affects antioxidant capacity and lipid profile in orchidectomized rats. Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n = 8) and an orchidectomized group (n = 24). The orchidectomized group was divided into three groups of eight and assigned to one of the following treatments: orchidectomy, orchidectomy plus 27% cranberry juice, and orchidectomy plus 45% cranberry juice. At 120 days after initiation of the study, all rats were killed, blood was collected, and plasma was harvested for total antioxidant status, malondialdehyde, nitrate + nitrite, and superoxide dismutase (SOD) activity in liver, and concentrations of cholesterol and triglyceride in liver and in plasma. Orchidectomy depressed (P < .05) plasma antioxidant capacity and SOD activity, elevated (P < .05) nitrate + nitrite and malondialdehyde in plasma, and increased (P < .05) triglyceride and cholesterol values in liver and in plasma. Cranberry juice increased (P < .05) plasma antioxidant capacity and SOD activity and reduced (P < .05) nitrate + nitrite and malondialdehyde concentrations. Drinking cranberry juice did not affect cholesterol concentrations in liver and in plasma. Triglyceride concentration in plasma of orchidectomized rats that were drinking cranberry juice increased (P < .05), but its concentration in liver decreased (P < .05) to the level of shams. The protective effect of cranberry juice from oxidative damage may be mediated by a decrease in nitrate + nitrite and dose-dependent decrease in peroxidation.

Ambient and at-the-ear occupational noise exposure and serum lipid levels.

PubMed

Arlien-Søborg, Mai C; Schmedes, Astrid S; Stokholm, Z A; Grynderup, M B; Bonde, J P; Jensen, C S; Hansen, Å M; Frederiksen, T W; Kristiansen, J; Christensen, K L; Vestergaard, J M; Lund, S P; Kolstad, H A

2016-10-01

Occupational and residential noise exposure has been related to increased risk of cardiovascular disease. Alteration of serum lipid levels has been proposed as a possible causal pathway. The objective of this study was to investigate the relation between ambient and at-the-ear occupational noise exposure and serum levels of total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and triglycerides when accounting for well-established predictors of lipid levels. This cross-sectional study included 424 industrial workers and 84 financial workers to obtain contrast in noise exposure levels. They provided a serum sample and wore portable dosimeters that every 5-s recorded ambient noise exposure levels during a 24-h period. We extracted measurements obtained during work and calculated the full-shift mean ambient noise level. For 331 workers who kept a diary on the use of a hearing protection device (HPD), we subtracted 10 dB from every noise recording obtained during HPD use and estimated the mean full-shift noise exposure level at the ear. Mean ambient noise level was 79.9 dB (A) [range 55.0-98.9] and the mean estimated level at the ear 77.8 dB (A) [range 55.0-94.2]. Ambient and at-the-ear noise levels were strongly associated with increasing levels of triglycerides, cholesterol-HDL ratio, and decreasing levels of HDL-cholesterol, but only in unadjusted analyses that did not account for HPD use and other risk factors. No associations between ambient or at-the-ear occupational noise exposure and serum lipid levels were observed. This indicates that a causal pathway between occupational and residential noise exposure and cardiovascular disease does not include alteration of lipid levels.

Myocardial potency of Bio-tea against Isoproterenol induced myocardial damage in rats.

PubMed

Lobo, Reema Orison; Shenoy, Chandrakala K

2015-07-01

Kombucha (Bio-tea) is a beverage produced by the fermentation of sugared black tea using a symbiotic association of bacteria and yeasts. Traditional claims about Kombucha report beneficial effects such as antibiotic properties, gastric regulation, relief from joint rheumatism and positive influence on the cholesterol level, arteriosclerosis, diabetes, and aging problems. The present investigation was carried out to understand the preventive effect of Kombucha on heart weight, blood glucose, total protein, lipid profile and cardiac markers in rats with myocardial damage induced using Isoproterenol. As Bio-tea is produced by fermenting tea, the parameters were compared in rats pre-treated with normal black tea and Bio-tea for 30 days followed by subcutaneous injection of Isoproterenol (85 mg/kg body weight). Normal rats as well as Isoproterenol induced myocardial infarcted rats were also used, which served as controls. Isoproterenol induced myocardial infarcted control rats showed a significant increase in heart weight, blood glucose and cardiac markers and a decrease in plasma protein. Increased levels of cholesterol, triglycerides, low density lipids (LDL) and very low density lipids (VLDL) were also observed, while the high density lipid (HDL) content decreased. Bio-tea showed a higher preventive effect against myocardial infarction when compared to tea, as was observed by the significant reduction in heart weight, and blood glucose and increase in plasma albumin levels. Bio-tea significantly decreased cholesterol, triglycerides, LDL and VLDL while simultaneously increasing the levels of HDL. Similarly a decrease in leakage of cardiac markers from the myocardium was also observed.

Fasting Lipoprotein Lipase Protein Levels Can Predict a Postmeal Increment of Triglyceride Levels in Fasting Normohypertriglyceridemic Subjects.

PubMed

Tsuzaki, Kokoro; Kotani, Kazuhiko; Yamada, Kazunori; Sakane, Naoki

2016-09-01

Although a postprandial increment in triglyceride (TG) levels is considered to be a risk factor for atherogenesis, tests (e.g., fat load) to assess postprandial changes in TG levels cannot be easily applied to clinical practice. Therefore, fasting markers that predict postprandial TG states are needed to be developed. One current candidate is lipoprotein lipase (LPL) protein, a molecule that hydrides TGs. This study investigated whether fasting LPL levels could predict postprandial TG levels. A total of 17 subjects (11 men, 6 women, mean age 52 ± 11 years) with normotriglyceridemia during fasting underwent the meal test. Several fasting parameters, including LPL, were measured for the area under the curve of postprandial TGs (AUC-TG). The subjects' mean fasting TG level was 1.30 mmol/l, and their mean LPL level was 41.6 ng/ml. The subjects' TG levels increased after loading (they peaked after two postprandial hours). Stepwise multiple regression analysis demonstrated that fasting TG levels were a predictor of the AUC-TG. In addition, fasting LPL mass levels were found to be a predictor of the AUC-TG (β = 0.65, P < 0.01), and this relationship was independent of fasting TG levels. Fasting LPL levels may be useful to predict postprandial TG increment in this population. © 2015 Wiley Periodicals, Inc.

Adenovirus 36 Seropositivity is Strongly Associated With Race and Gender, But Not Obesity, Among U.S. Military Personnel

DTIC Science & Technology

2010-01-01

relationship between Ad-36 exposure and (1) obesity, and (2) levels of serum cholesterol and triglycerides . In this study there was no association in...value 0.0075), female gender (P-value 0.036), and a lower frequency of high levels of low- density lipoproteins (P-value 0.013). Logistic regression...levels of / cholesterol and triglycerides . There was no association in either case. Unanticipated relationships between Ad-36 exposure and age, race

Circadian disruption promotes tumor growth by anabolic host metabolism; experimental evidence in a rat model.

PubMed

Guerrero-Vargas, Natalí N; Navarro-Espíndola, Raful; Guzmán-Ruíz, Mara A; Basualdo, María Del Carmen; Espitia-Bautista, Estefania; López-Bago, Ana; Lascurain, Ricardo; Córdoba-Manilla, Cinthya; Buijs, Ruud M; Escobar, Carolina

2017-09-06

Light at night creates a conflicting signal to the biological clock and disrupts circadian physiology. In rodents, light at night increases the risk to develop mood disorders, overweight, disrupted energy metabolism, immune dysfunction and cancer. We hypothesized that constant light (LL) in rats may facilitate tumor growth via disrupted metabolism and increased inflammatory response in the host, inducing a propitious microenvironment for tumor cells. Male Wistar rats were exposed to LL or a regular light-dark cycle (LD) for 5 weeks. Body weight gain, food consumption, triglycerides and glucose blood levels were evaluated; a glucose tolerance test was also performed. Inflammation and sickness behavior were evaluated after the administration of intravenous lipopolysaccharide. Tumors were induced by subcutaneous inoculation of glioma cells (C6). In tumor-bearing rats, the metabolic state and immune cells infiltration to the tumor was investigated by using immunohistochemistry and flow cytometry. The mRNA expression of genes involved metabolic, growth, angiogenes and inflammatory pathways was measured in the tumor microenvironment by qPCR. Tumor growth was also evaluated in animals fed with a high sugar diet. We found that LL induced overweight, high plasma triglycerides and glucose levels as well as reduced glucose clearance. In response to an LPS challenge, LL rats responded with higher pro-inflammatory cytokines and exacerbated sickness behavior. Tumor cell inoculation resulted in increased tumor volume in LL as compared with LD rats, associated with high blood glucose levels and decreased triglycerides levels in the host. More macrophages were recruited in the LL tumor and the microenvironment was characterized by upregulation of genes involved in lipogenesis (Acaca, Fasn, and Pparγ), glucose uptake (Glut-1), and tumor growth (Vegfα, Myc, Ir) suggesting that LL tumors rely on these processes in order to support their enhanced growth. Genes related with the inflammatory state in the tumor microenvironment were not different between LL and LD conditions. In rats fed a high caloric diet tumor growth was similar to LL conditions. Data indicates that circadian disruption by LL provides a favorable condition for tumor growth by promoting an anabolic metabolism in the host.

Lipids analysis in hemolymph of African giant Achatina fulica (Bowdich, 1822) exposed to different photoperiods.

PubMed

Lustrino, D; Tunholi-Alves, V M; Tunholi, V M; Marassi, M P; Pinheiro, J

2010-02-01

The influence of different photophases (0, 6, 12, 18 and 24 hours) on the triglycerides and total cholesterol contents in the hemolymph of A. fulica was evaluated, since there is no information in the literature about the influence of this factor on lipids metabolism in mollusks. After 2 and 4 weeks of exposure the snails were dissected. The cholesterol content at the 2nd and 4th weeks post exposure only varied significantly in the groups exposed at 24 hours and 0 hour of photophase, respectively. Probably, such increase may be a result of a rise in cholesterol biosynthesis and/or remodelling of cell membranes. There were no significant differences among the content of triglycerides in the snails exposed to 6, 12, 18 and 24 hours of photophase during two weeks. The snails exposed to intermediate photophase (6 and 12 hours) had the triglycerides content increased, ranging over values near to those observed in the group exposed to 0 hour. Results showed that triglycerides metabolism in A. fulica are more influenced by photoperiod than cholesterol metabolism. A negative relation is maintained between the triglycerides content in the hemolymph and the different photophases, with lower mobilisation of triglycerides under shorter photophases.

Factors Related to Urinary Incontinence among the Malaysian Elderly.

PubMed

Eshkoor, S A; Hamid, T A; Shahar, S; Mun, C Y

2017-01-01

Urinary incontinence is a prevalent condition in the elderly that is the spontaneous leakage of urine. It is an age-related problem and increases especially in people aged above 65 years. It can cause many psychological, behavioral, biological, economic and social effects. The treatment of urinary incontinence can reduce morbidity and mortality. Thus, this study aimed to determine the effects of variables including age, ethnicity, gender, education, marital status, body weight, blood elements and nutritional parameters on urinary incontinence among the Malaysian elderly. The study was on 2322 non-institutionalized Malaysian elderly. The hierarchy logistic regression analysis was applied to estimate the risk of independent variables for urinary incontinence among respondents. The findings indicated that approximately 3.80% of subjects had urinary incontinence. In addition, constipation was found a significant factor that increased the risk of urinary incontinence in samples (p=0.006; OR=3.77). The increase in dietary monounsaturated fat (p=0.038; OR=0.59) and plasma triglyceride levels (p=0.029; OR=0.56) significantly reduced the risk of incontinence in subjects. Many of suspected variables including socio-demographic factors, diseases, nutritional minerals, blood components and body weight were non-relevant factors to urinary incontinence in respondents. Constipation increased the risk of urinary incontinence in subjects, and increase in dietary monounsaturated fat and plasma triglyceride levels decreased the risk.

Significance of platelet-activating factor acetylhydrolase in patients with non-insulin-dependent (type 2) diabetes mellitus.

PubMed

Serban, M; Tanaseanu, Cristina; Kosaka, T; Vidulescu, Cristina; Stoian, Irina; Marta, Daciana S; Tanaseanu, S; Moldoveanu, Elena

2002-01-01

Non-insulin dependent diabetes mellitus (NIDDM) represents an independent risk factor for cardiovascular diseases (CVD), being characterized by a continuous low-grade inflammation and endothelial activation state. Plasma platelet - activating factor - acetylhydrolases (PAF-AHs) are a subgroup of Ca(2+)-independent phospholipase A(2) family (also known as lipoprotein-associated phospholipases A(2)) that hydrolyze and inactivate the lipid mediator platelet-activating factor (PAF) and/or oxidized phospholipids. This enzyme is considered to play an important role in inflammatory diseases and atherosclerosis. The present study aims to investigate the relations between the levels of PAF-AH activity and LDL-cholesterol / HDL-cholesterol (LDL-ch / HDL-ch) ratio in NIDDM patients as compared to controls. serum PAF-AH activity was measured in 50 patients with dyslipidemia, in 50 NIDDM patients and in 50 controls (normal lipid and glucose levels). Total cholesterol, LDL-ch, HDL-ch, triglyceride and blood glucose were determined in all subjects. All NIDDM patients display hiperlipidemia, with increased LDL-ch and triglyceride levels. There is a significant correlation between LDL-ch levels (especially LDL-ch / HDL-ch ratio) and PAF-AH activity in dyslipidemic and NIDDM patients. Diabetic and dyslipidemic patients have an increased plasma PAF-AH activity correlated with their LDL-ch levels and mainly with LDL-ch / HDL-ch ratio. Plasma PAF-AH high levels appear to be important as a risk marker for endothelial dysfunction in patients with NIDDM.

Fasting energy homeostasis in mice with adipose deficiency of desnutrin/adipose triglyceride lipase.

PubMed

Wu, Jiang Wei; Wang, Shu Pei; Casavant, Stéphanie; Moreau, Alain; Yang, Gong She; Mitchell, Grant A

2012-05-01

Adipose triglyceride lipase (ATGL) catalyzes the first step of lipolysis of cytoplasmic triacylglycerols in white adipose tissue (WAT) and several other organs. We created adipose-specific ATGL-deficient (ATGLAKO) mice. In these mice, in vivo lipolysis, measured as the increase of plasma nonesterified fatty acid and glycerol levels after injection of a β3-adrenergic agonist, was undetectable. In isolated ATGLAKO adipocytes, β3-adrenergic-stimulated glycerol release was 10-fold less than in controls. Under fed conditions, ATGLAKO mice had normal viability, mild obesity, low plasma nonesterified fatty acid levels, increased insulin sensitivity, and increased daytime food intake. After 5 h of fasting, ATGLAKO WAT showed phosphorylation of the major protein kinase A-mediated targets hormone-sensitive lipase and perilipin A and ATGLAKO liver showed low glycogen and triacylglycerol contents. During a 48-h fast, ATGLAKO mice developed striking and complex differences from controls: progressive reduction of oxygen consumption, high respiratory exchange ratio, consistent with reduced fatty acid availability for energy production, lethargy, hypothermia, and undiminished fat mass, but greater loss of lean mass than controls. Plasma of 48 h-fasted ATGLAKO mice had a unique pattern: low 3-hydroxybutyrate, insulin, adiponectin, and fibroblast growth factor 21 with elevated leptin and corticosterone. ATGLAKO WAT, liver, skeletal muscle, and heart showed increased levels of mRNA related to autophagy and proteolysis. In murine ATGL deficiency, adipose lipolysis is critical for fasting energy homeostasis, and fasting imposes proteolytic stress on many organs, including heart and skeletal muscle.

Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

PubMed Central

Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C.; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B.

2016-01-01

The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID:27399766

Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice.

PubMed

Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B

2016-07-07

The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 10⁸ cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions.

Plasma lipid metabolites and refueling performance of Semi palmated Sandpipers at migratory stopovers

USGS Publications Warehouse

Lyons, J.E.; Collazo, J.A.; Guglielmo, C.

2005-01-01

Assessing stopover habitat quality and refueling performance of individual birds is crucial to the conservation and management of migratory shorebirds. Plasma lipid metabolites indicate the trajectory of mass change in individuals and may be a more accurate measure of refueling performance at a particular site than static measures such as nutrient reserves. We measured lipid metabolites of Semipalmated Sandpipers at 4 coastal stopover sites during northward migration: Merritt Island, FL; Georgetown, SC; Pea Island, NC; and Delaware Bay, NJ. We described spatial and temporal variation in metabolic profiles among the 4 stopovers and evaluated the effects of body mass, age, and date on metabolite concentrations. Triglyceride concentration, an indicator of fat deposition, declined during the migration, whereas B-OH-Butyrate, a measure of fasting, increased. Triglyceride concentration correlated with phospholipids and inversely related to B-OH-butyrate, but was not related to body mass or age. Triglyceride levels and estimated percent fat were greater at Delaware Bay than at any stopovers to the south. Plasma metabolite profiles accurately reflected stopover refueling performance and provide an important new technique for assessing stopover habitat quality for migratory shorebirds.

Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

PubMed Central

Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F.

2011-01-01

Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743

Antilipogenic and hypolipidemic effects of ethanol extracts from two variants of Artemisia princeps Pampanini in obese diabetic mice.

PubMed

Jung, Un Ju; Baek, Nam-In; Chung, Hae-Gon; Jeong, Tae-Sook; Lee, Kyung Tae; Lee, Mi-Kyung; Choi, Myung-Sook

2009-12-01

The objective of this study was to determine the effects of the ethanol extract of two variants of Artemisia princeps Pampanini, Sajabalssuk (SB) and Sajuarissuk (SS), on lipid metabolism in type 2 diabetic animals. Male C57BL/KsJ-db/db mice were divided into control, SB ethanol extract (SBE) (0.171 g/100 g of diet), SS ethanol extract (SSE) (0.154 g/100 g of diet), and rosiglitazone (RG) (0.005 g/100 g of diet) groups. Supplementation of SBE and SSE significantly lowered the plasma levels of free fatty acid, triglyceride, and total cholesterol compared to the control group. The hepatic triglyceride and cholesterol contents and hepatic lipid droplets accumulation were also significantly lower in the SBE- and SSE-supplemented db/db mice than in the control or RG-supplemented db/db mice. Reductions of hepatic triglyceride and cholesterol contents in the SBE and SSE groups were related to the suppression of hepatic lipogenic enzyme activities, fatty acid synthesis (fatty acid synthase and malic enzyme), triglyceride synthesis (phosphatidate phosphohydrolase), and cholesterol synthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase) and esterification (acyl-coenzyme A:cholesterol acyltransferase). The RG supplement lowered plasma and hepatic lipid levels compared to the control group. However, RG significantly increased the white and brown adipose tissue weight and epididymal adipocyte size, whereas SBE and SSE lowered the brown adipose tissue weight and epididymal adipocyte size compared to the RG group. Together, these data suggest that supplementation of SBE and SSE partly improves lipid dysregulation and fatty liver in db/db mice by suppressing hepatic lipogenic enzyme activities.

Effect of weight loss on the postprandial response to high-fat and high-carbohydrate meals in obese women.

PubMed

Dallongeville, J; Gruson, E; Dallinga-Thie, G; Pigeyre, M; Gomila, S; Romon, M

2007-06-01

To assess the effect of weight loss on the plasma lipid and remnant-like lipoprotein cholesterol (RLPc) response to a high-fat or a high-carbohydrate meal in a population of obese women. Nutritional intervention study. Sixteen obese women (mean body mass index (BMI): 37.6+/-5 kg/m(2)). Subjects were asked to follow an energy-restricted diet (800 kcal/day) for 7 weeks, followed by a 1-week maintenance diet. Before and after weight loss, each participant was given (in random order) two iso-energetic meals containing either 80% fat and 20% protein (the high-fat meal) or 80% carbohydrate and 20% protein (the high-carbohydrate meal). Blood samples were collected over the following 10-h period. A two-way analysis of variance with repeated measures was used to assess the effect of the meal and postprandial time on biological variables and postprandial responses (notably RLPc levels). Weight loss was associated with a significant decrease in fasting triglyceride (P=0.0102), cholesterol (P<0.0001), low-density lipoprotein cholesterol (P=0.0003), high-density lipoprotein-cholesterol (P=0.0009) and RLPc (P=0.0015) levels. The triglyceride response to the high-fat meal was less intense after weight reduction than before (interaction P<0.002). This effect persisted after adjustment on baseline triglyceride levels. The triglyceride response to the high-carbohydrate meal was biphasic (i.e. with two peaks, 1 and 6 h after carbohydrate intake). After adjustment on baseline values, weight reduction was associated with a trend towards a reduction in the magnitude of the second triglyceride peak (interaction P<0.054). In contrast, there was no difference in postprandial RLPc responses before and after weight loss, again after adjustment on baseline levels. Our data suggest that weight loss preferentially affects postprandial triglyceride metabolism.

Plasma thyroxine changes of the Apollo Crewman.

PubMed

Sheinfeld, M; Leach, C S; Johnson, P C

1975-01-01

Blood drawn from Apollo crew member; to the mission, at recovery, and postmission was used to examine the effect Apollo mission activities have on tyroid hormone levels. At recovery, statistically significant increases in thyroxine and the free thyroxine index were found. Serum cholesterol and triglycerides were decreased. No change of statistical significance was found in the T3 binding percentage, total serum proteins, and albumin. We conclude that apollo activities and environment caused the postmission increase in serum cholesterol may be one result of the increased thyroxine activity.

Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease.

PubMed

Croteau, Etienne; Castellano, Christian-Alexandre; Richard, Marie Anne; Fortier, Mélanie; Nugent, Scott; Lepage, Martin; Duchesne, Simon; Whittingstall, Kevin; Turcotte, Éric E; Bocti, Christian; Fülöp, Tamàs; Cunnane, Stephen C

2018-06-09

In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement. To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults. Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (11C-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention. Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization. Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.

Moderate alcohol consumption and changes in postprandial lipoproteins of premenopausal and postmenopausal women: a diet-controlled, randomized intervention study.

PubMed

van der Gaag, M S; Sierksma, A; Schaafsma, G; van Tol, A; Geelhoed-Mieras, T; Bakker, M; Hendriks, H F

2000-01-01

Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Earlier studies in men have shown that moderate alcohol consumption affects lipoprotein metabolism and hemostasis. In this diet-controlled, randomized, crossover trial, we investigated the effect on lipoprotein metabolism of moderate consumption of red wine or red grape juice with evening dinner for 3 weeks in premenopausal women using oral contraceptives and in postmenopausal women. After 3 weeks, blood samples were collected 1 hour before dinner up to 19 hours after starting dinner at 2-hour or 4-hour intervals. Plasma triglyceride concentrations and very low density lipoprotein (VLDL) triglyceride levels peaked 3 hours after dinner with wine in both premenopausal and postmenopausal women. After wine consumption, the overall high-density lipoprotein (HDL) cholesterol level was increased in postmenopausal women (mean increase 0.17 mmol/L, or 12%, p = 0.03), and the plasma low-density lipoprotein (LDL) cholesterol level was reduced in premenopausal women (mean reduction 0.35 mmol/L, or 12%, p = 0.01) as compared with grape juice consumption. The findings suggest that postprandial lipoprotein metabolism after moderate alcohol consumption differs between oral contraceptive-using premenopausal women and postmenopausal women. The response of postmenopausal women to alcohol resembled the response found in earlier studies in men.

Evaluation of Lipid Profile in Patients with Cherry Angioma: A Case-Control Study in Guilan, Iran.

PubMed

Darjani, Abbas; Rafiei, Rana; Shafaei, Sareh; Rafiei, Elahe; Eftekhari, Hojat; Alizade, Narges; Gharaei Nejad, Kaveh; Rafiee, Behnam; Najirad, Sara

2018-01-01

Cherry angioma is the most common type of acquired cutaneous vascular proliferation which would increase with aging due to some angiogenic factors but the exact pathogenesis is unknown. Usually angiogenic factors are synthesized in human body to compensate occlusive effects of atherogenic agents such as serum lipids. Our hypothesis was that increased levels of these angiogenic factors could be a trigger for development of cherry angioma. This study has been designed to compare frequency of dyslipidemia in subjects with and without cutaneous cherry angioma. In this case-control study, 122 cases with cherry angioma and 122 control subjects without cherry angioma were enrolled. Demographic characteristics, number of the cherry angioma lesions, and serum lipid profile were collected for all subjects. The data was analyzed using SPSS 18 software. Mean levels of the total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were higher in patients with cherry angioma compared to control subjects in which differences were significant for total cholesterol, low-density lipoprotein, and triglyceride ( P < 0.05) but not for high-density lipoprotein level. Serum lipids may have a role in producing angiogenic factors and development of cherry angioma and it seems logical to evaluate lipid profile in these cases.

[Postprandial lipemia as an atherosclerotic risk factor and fat tolerance test].

PubMed

Ishikawa, T

1999-12-01

Most of our lives are spent in the postprandial state, during which vessel walls are exposed to triglyceride rich lipoproteins-namely, chylomicron and chylomicron remnants. Recent studies showed that coronary artery disease patients even with normal fasting lipid levels had higher concentrations of postprandial lipoproteins than patients without coronary artery disease. Postprandial lipoprotein responses are influenced by various factors such as the postabsorptive concentrations of plasma triglycerides, lipoprotein lipase activity, polymorphisms of apolipoprotein B and apolipoprotein E, dietary fatty acid contents. Oral fat tolerance test is performed to see the postprandial lipoprotein responses. Triglycerides, apolipoprotein B, retinyl-palmitate and remnant like particles in plasma and subfractionated triglyceride rich lipoproteins are measured.

Effects of a westernized lifestyle on the association between fasting serum nonesterified fatty acids and insulin secretion in Japanese men.

PubMed

Kamei, Nozomu; Yamane, Kiminori; Nakanishi, Shuhei; Ishida, Kazufumi; Ohtaki, Megu; Okubo, Masamichi; Kohno, Nobuoki

2005-06-01

The effects of the prolonged elevation of nonesterified fatty acid (NEFA) levels on insulin secretion have been controversial and thought to be sex-specific. To investigate the association between a westernized lifestyle and the effects of NEFA on insulin secretion in Japanese men, we examined 67 nondiabetic Japanese-American men and 220 nondiabetic native Japanese men who underwent a 75-g oral glucose tolerance test (OGTT). Most Japanese Americans we surveyed are genetically identical to Japanese living in Japan, but their lifestyle is more westernized. Sets of multiple regression analyses were performed to evaluate the relationship between the sum of the immunoreactive insulin (IRI) levels during the OGTT ((Sigma)IRI) and clinical parameters. Japanese Americans had higher levels of fasting IRI, (Sigma)IRI, and a higher insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]) than native Japanese, whereas there were no significant differences in fasting NEFA and triglyceride levels. A multiple regression analysis adjusted for age, fasting triglycerides, and body mass index (BMI) demonstrated that the fasting NEFA level was an independent determinant of the (Sigma)IRI only in Japanese-American men ( P = .001), but not in native Japanese men ( P = .054). Even when HOMA-IR was included in models instead of BMI, the NEFA level was a significant variable of (Sigma)IRI only in Japanese Americans ( P < .001), and not in native Japanese ( P = .098). In addition, a multiple regression analysis adjusted for age, fasting triglycerides, and BMI demonstrated that the fasting NEFA level was the only independent determinant of (Sigma)C-peptide in Japanese-American men ( P = .041). In conclusion, NEFA seems to be associated with insulin secretion independent of obesity or HOMA-IR. A westernized lifestyle may increase the effects of serum fasting NEFA levels on total insulin secretion after a glucose load in Japanese men.

[Abnormal metabolism of triglycerides fractions in chronic pancreatitis and results after the operation treatment].

PubMed

Diakowska, Dorota; Knast, Witold; Diakowski, Witold; Grabowski, Krzysztof; Szelachowski, Piotr; Pelczar, Piotr

2005-06-01

This study was undertaken to determine how fats digestion processes were damaged due to chronic pancreatitis, and identify, whether lipid metabolism improved after surgical treatment the patients with chronic pancreatitis. Total lipids, triglycerides, diglycerides and free fatty acids levels in serum and stool were analysed, using chemical tests, thin-layer chromatography and electrophoresis of serum lipoproteins. The patients before the operations showed higher total lipids and triglycerides concentrations, and lower concentrations of diglycerides and free fatty acids in stool. These patients had high triglycerides, chylomicrons, VLDL, LDL-CH concentrations, and low-diglycerides, free fatty acids, HDL-CH concentrations in serum. These data were statistically significant. After the operations and substitution therapy it was observed normalization of the total lipids and lipids fractions levels in stool and in serum. Concentrations of LDL-CH and HDL-CH fractions were irregular. We conclude, that these lipids parameters could be used in diagnosing and monitoring the results of chronic pancreatitis surgical treatment.

Effect of aqueous bark extract of Garuga pinnata Roxb. in streptozotocin-nicotinamide induced type-II diabetes mellitus.

PubMed

Shirwaikar, Annie; Rajendran, K; Barik, Rakesh

2006-09-19

A study was undertaken to evaluate the antihyperglycemic activity of aqueous extract of bark of Garuga pinnata Roxb. (Burseraceae). The various parameters studied included fasting blood sugar levels, serum lipid levels, liver glycogen content, serum insulin level and glycated hemoglobin in diabetic and normal rats. Streptozotocin-nicotinamide was used to induce type-II diabetes mellitus. Treatment with the extract at two dose levels showed a significant increase in the liver glycogen and serum insulin level and a significant decrease in fasting blood glucose and glycated hemoglobin levels. The total cholesterol and serum triglycerides levels were also significantly reduced and the HDL cholesterol levels were significantly increased upon treatment with the extract thus proving the potent antidiabetic property of the plant.

Biomechanism of chlorogenic acid complex mediated plasma free fatty acid metabolism in rat liver.

PubMed

H V, Sudeep; K, Venkatakrishna; Patel, Dipak; K, Shyamprasad

2016-08-05

Plasma free fatty acids (FFA) are involved in blood lipid metabolism as well as many health complications. The present study was conducted to evaluate the potential role of chlorogenic acid complex from green coffee bean (CGA7) on FFA metabolism in high fat diet fed rats. Hyperlipidemia was induced in Wistar rats using high-fat diet. The animals were given CGA7/orlistat concurrently for 42 days. The parameters analysed during the study include plasma and liver total cholesterol (TC), Triglycerides (TG) and FFA. AMPK activation in the liver was analysed through ELISA. The multiple factors involved in AMPK mediated FFA metabolism were analysed using western blotting. CGA7 (50, 100, 150 mg/kg BW) decreased triglycerides (TG) and FFA levels in plasma and liver. CGA7 administration led to the activation of AMP-activated protein kinase (AMPK) and a subsequent increase in the levels of carnitine palmitoyltransferase 1 (CPT-1). There was a decrease in acetyl-CoA carboxylase (ACC) activity as evident by the increase in its phosphorylation level. Chlorogenic acids improved the blood lipid metabolism in rats by alleviating the levels of FFA and TG, modulating the multiple factors in liver through AMPK pathway. The study concludes that CGA7 complex can be promoted as an active ingredient in nutrition for obesity management.

Novel natural food colourant G8000 benefits LDL- and HDL-cholesterol in humans.

PubMed

Peres, Rogerio Correa; Gollücke, Andrea Pitelli Boiago; Soares, Clayton; Machado, Patricia; Viveiros Filho, Vitor; Rocha, Silvana; Morais, Damila Rodrigues; Bataglion, Giovana Anceski; Eberlin, Marcos Nogueira; Ribeiro, Daniel Araki

2015-01-01

The aim of this study was to investigate the phenolic composition of a natural food colourant (G8000™) as well as its effects on plasma markers after 28-day consumption by healthy individuals at a dietary dose (70 g). Parameters of total cholesterol and its fractions, triglycerides and plasma enzymes biomarkers of muscle injury were measured. Major compounds identified in G8000™ by ESI-MS showed the presence of anthocyanins, organic acids, phenolic acids as well as monosaccharides. HDL levels significantly increased from 43 ± 10.2 mg/dL to 95 ± 16.9 mg/dL. LDL levels significantly decreased from 110 ± 40.9 mg/dL to 69 ± 39 mg/dL (p < 0.001). No significant statistical differences (p > 0.05) were observed for total cholesterol, triglycerides and VLDL. After the intake, plasma enzyme CK-MB decreased from 20 ± 12.1 U/L to 10 ± 1.9 U/L while LDH levels increased from 275 ± 124.4 U/L to 317 ± 114.7 U/L (p < 0.005). No significant differences were observed for CK levels. Taken together, dietary intake of natural colourant G8000™ was able to exert beneficial effects on atherosclerosis biomarkers.