Plasma folate levels and associated factors in women planning to become pregnant in a population with high prevalence of neural tube defects.

PubMed

Ma, Rui; Wang, Linlin; Jin, Lei; Li, Zhiwen; Ren, Aiguo

2017-07-17

Optimal blood folate levels of women before pregnancy are critical to the prevention of neural tube defects (NTDs). However, few studies have focused on blood folate levels of women planning to become pregnant. The aims of this study were to assess plasma folate levels in women who planned to become pregnant in a population with high prevalence of NTDs, to identify factors associated with plasma folate levels, and to evaluate the risk of NTDs at the population level. A total of 2065 women were enrolled at the time of premarital health check-up in two rural counties in northern China from November 2009 to December 2012. Fasting venous blood samples were collected and plasma folate concentrations were measured by microbiological method. The overall median of plasma folate was 10.5 nmol/L. 50% of the women had a plasma folate level below 10.5 nmol/L, a cutoff for megaloblastic anemia, and 88% below 18 nmol/L, a proposed optimal plasma folate level for the prevention of NTDs. Folic acid supplementation was the only factor to be associated with plasma folate concentrations, but only 1.9% of the women reported having taken folic acid supplements. A population risk of 29.3 NTD cases per 10,000 births was predicted. Women who planned to become pregnant had very low plasma folate in the population. Folic acid supplementation was the only factor to be associated with a high plasma folate concentration. High NTD risk would remain if women would get pregnant without having taken folic acid supplements. Birth Defects Research 109:1039-1047, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Plasma folate levels in early to mid pregnancy after a nation-wide folic acid supplementation program in areas with high and low prevalence of neural tube defects in China.

PubMed

Liu, Jufen; Gao, Lili; Zhang, Yali; Jin, Lei; Li, Zhiwen; Zhang, Le; Meng, Qinqin; Ye, Rongwei; Wang, Linlin; Ren, Aiguo

2015-06-01

Folic acid supplementation is recommended for all women of child-bearing age to prevent neural tube defects (NTDs). A nation-wide folic acid supplementation program was implemented in rural areas of China since 2009; however, changes in plasma folate levels in pregnant women were unknown. A cross-sectional survey was conducted in 2011 to 2012, with 1736 pregnant women enrolled, and results were compared with a previous survey in 2002 to 2004. A microbiological method was used to determine plasma folate levels. Preprogram and postprogram median plasma folate concentrations were compared while stratified by prevalence of NTDs and residence. In the high NTD prevalence population, plasma folate concentration increased to 33.4 (18.7, 58.4) nmol/L in the postprogram sample, which is 2.9 times of the preprogram. In the low NTD prevalence population, plasma folate increased to 67.9 (44.5, 101.9) nmol/L, which is 1.9 times of the preprogram. Gaps remained in plasma folate levels with respect to prevalence of NTDs and residence. Folic acid supplementation has a strong impact on plasma folate concentrations. Earlier supplementation (before the last menstrual period), increased supplementation frequency and more total days of supplementation were associated with a higher plasma folate concentration as demonstrated in both the high- and low-prevalence populations. Plasma folate levels among pregnant Chinese women increased dramatically after the nation-wide folic acid supplementation program in both rural and urban areas, and in populations of high and low NTD prevalence. The nation-wide program should have a component to ensure that supplementation begins before pregnancy. © 2015 Wiley Periodicals, Inc.

Elevated Prostaglandin E Metabolites and Abnormal Plasma Fatty Acids at Baseline in Pediatric Cystic Fibrosis Patients: A Pilot Study

PubMed Central

O’Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F.; Laposata, Michael; Seegmiller, Adam

2016-01-01

Background Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). Methods This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6 to 18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Results Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Conclusions Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. PMID:27720040

Elevated prostaglandin E metabolites and abnormal plasma fatty acids at baseline in pediatric cystic fibrosis patients: a pilot study.

PubMed

O'Connor, Michael Glenn; Thomsen, Kelly; Brown, Rebekah F; Laposata, Michael; Seegmiller, Adam

2016-10-01

Airway inflammation is a significant contributor to the morbidity of cystic fibrosis (CF) disease. One feature of this inflammation is the production of oxygenated metabolites, such as prostaglandins. Individuals with CF are known to have abnormal metabolism of fatty acids, typically resulting in reduced levels of linoleic acid (LA) and docosahexaenoic acid (DHA). This is a randomized, double-blind, cross-over clinical trial of DHA supplementation with endpoints of plasma fatty acid levels and prostaglandin E metabolite (PGE-M) levels. Patients with CF age 6-18 years with pancreatic insufficiency were recruited. Each participant completed 3 four-week study periods: DHA at two different doses (high dose and low dose) and placebo with a minimum 4 week wash-out between each period. Blood, urine, and exhaled breath condensate (EBC) were collected at baseline and after each study period for measurement of plasma fatty acids as well as prostaglandin E metabolites. Seventeen participants were enrolled, and 12 participants completed all 3 study periods. Overall, DHA supplementation was well tolerated without significant adverse events. There was a significant increase in plasma DHA levels with supplementation, but no significant change in arachidonic acid (AA) or LA levels. However, at baseline, AA levels were lower and LA levels were higher than previously reported for individuals with CF. Urine PGE-M levels were elevated in the majority of participants at baseline, and while levels decreased with DHA supplementation, they also decreased with placebo. Urine PGE-M levels are elevated at baseline in this cohort of pediatric CF patients, but there was no significant change in these levels with DHA supplementation compared to placebo. In addition, baseline plasma fatty acid levels for this cohort showed some difference to prior reports, including higher levels of LA and lower levels of AA, which may reflect changes in clinical care, and consequently warrants further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plasma Amino Acids Profiles in Children with Autism: Potential Risk of Nutritional Deficiencies.

ERIC Educational Resources Information Center

Arnold, Georgianne L.; Hyman, Susan L.; Mooney, Robert A.; Kirby, Russell S.

2003-01-01

The plasma amino acid profiles of 10 children with autism on gluten and casein restricted diets and 26 on unrestricted diets were reviewed. There was a trend for the children on restricted diets to have an increased prevalence of essential amino acid deficiencies and lower plasma levels of essential acids. (Contains references.) (Author/CR)

Increased plasma citrulline in mice marks diet-induced obesity and may predict the development of the metabolic syndrome.

PubMed

Sailer, Manuela; Dahlhoff, Christoph; Giesbertz, Pieter; Eidens, Mena K; de Wit, Nicole; Rubio-Aliaga, Isabel; Boekschoten, Mark V; Müller, Michael; Daniel, Hannelore

2013-01-01

In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ) to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF) feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline) is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the "diabetic fingerprint" of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic impairments.

[The clinical value of measuring plasma level of very long chain fatty acids in Addison disease].

PubMed

Chen, Jun; Zhang, Jian; Wang, De-Xin

2007-09-01

To determine the level of very long chain fatty acids (VLCFA) in plasma to find out X-linked adrenoleukodystrophy (X-ALD) in patients with Addison disease. By using gas chromatography measurement of plasma levels of C(26:0), ratios of C(26:0)/C(22:0) and C(24:0)/C(22:0) was carried out in 36 patients with Addison disease. Among the 36 cases, 6 had elevated plasma VLCFA levels; thus the presence of X-ALD was confirmed. Misdiagnosis of X-ALD can be reduced by measuring plasma level of VLCFA early in male patients with Addison disease, especially in young ones.

Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

PubMed

Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

2014-07-01

The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.

Associations between fatty acid oxidation, hepatic mitochondrial function, and plasma acylcarnitine levels in mice.

PubMed

Bjørndal, Bodil; Alterås, Eva Katrine; Lindquist, Carine; Svardal, Asbjørn; Skorve, Jon; Berge, Rolf K

2018-01-01

The 4-thia fatty acid tetradecylthiopropionic acid (TTP) is known to inhibit mitochondrial β-oxidation, and can be used as chemically induced hepatic steatosis-model in rodents, while 3-thia fatty acid tetradecylthioacetic acid (TTA) stimulates fatty acid oxidation through activation of peroxisome proliferator activated receptor alpha (PPARα). We wished to determine how these two compounds affected in vivo respiration and mitochondrial efficiency, with an additional goal to elucidate whether mitochondrial function is reflected in plasma acylcarnitine levels. C57BL/6 mice were divided in 4 groups of 10 mice and fed a control low-fat diet, low-fat diets with 0.4% ( w /w) TTP, 0.4% TTA or a combination of these two fatty acids for three weeks ( n  = 10). At sacrifice, β-oxidation and oxidative phosphorylation (OXPHOS) capacity was analysed in fresh liver samples. Hepatic mitochondria were studied using transmission electron microscopy. Lipid classes were measured in plasma, heart and liver, acylcarnitines were measured in plasma, and gene expression was measured in liver. The TTP diet resulted in hepatic lipid accumulation, plasma L-carnitine and acetylcarnitine depletion and elevated palmitoylcarnitine and non-esterified fatty acid levels. No significant lipid accumulation was observed in heart. The TTA supplement resulted in enhanced hepatic β-oxidation, accompanied by an increased level of acetylcarnitine and palmitoylcarnitine in plasma. Analysis of mitochondrial respiration showed that TTP reduced oxidative phosphorylation, while TTA increased the maximum respiratory capacity of the electron transport system. Combined treatment with TTP and TTA resulted in a profound stimulation of genes involved in the PPAR-response and L-carnitine metabolism, and partly prevented triacylglycerol accumulation in the liver concomitant with increased peroxisomal β-oxidation and depletion of plasma acetylcarnitines. Despite an increased number of mitochondria in the liver of TTA + TTP fed mice, the OXPHOS capacity was significantly reduced. This study indicates that fatty acid β-oxidation directly affects mitochondrial respiratory capacity in liver. As plasma acylcarnitines reflected the reduced mitochondrial β-oxidation in TTP-fed mice, they could be useful tools to monitor mitochondrial function. As mitochondrial dysfunction is a major determinant of metabolic disease, this supports their use as plasma markers of cardiovascular risk in humans. Results however indicate that high PPAR activation obscures the interpretation of plasma acylcarnitine levels.

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.

Myeloperoxidase-derived 2-chlorofatty acids contribute to human sepsis mortality via acute respiratory distress syndrome.

PubMed

Meyer, Nuala J; Reilly, John P; Feng, Rui; Christie, Jason D; Hazen, Stanley L; Albert, Carolyn J; Franke, Jacob D; Hartman, Celine L; McHowat, Jane; Ford, David A

2017-12-07

Sepsis-associated acute respiratory distress syndrome (ARDS) is characterized by neutrophilic inflammation and poor survival. Since neutrophil myeloperoxidase (MPO) activity leads to increased plasma 2-chlorofatty acid (2-ClFA) levels, we hypothesized that plasma concentrations of 2-ClFAs would associate with ARDS and mortality in subjects with sepsis. In sequential consenting patients with sepsis, free 2-ClFA levels were significantly associated with ARDS, and with 30-day mortality, for each log increase in free 2-chlorostearic acid. Plasma MPO was not associated with either ARDS or 30-day mortality but was correlated with 2-ClFA levels. Addition of plasma 2-ClFA levels to the APACHE III score improved prediction for ARDS. Plasma 2-ClFA levels correlated with plasma levels of angiopoietin-2, E selectin, and soluble thrombomodulin. Endothelial cells treated with 2-ClFA responded with increased adhesion molecule surface expression, increased angiopoietin-2 release, and dose-dependent endothelial permeability. Our results suggest that 2-ClFAs derived from neutrophil MPO-catalyzed oxidation contribute to pulmonary endothelial injury and have prognostic utility in sepsis-associated ARDS.

Marine n-3 polyunsaturated fatty acids in patients with end-stage renal failure and in subjects without kidney disease: a comparative study.

PubMed

Madsen, Trine; Christensen, Jeppe H; Svensson, My; Witt, Petra M; Toft, Egon; Schmidt, Erik B

2011-03-01

Patients with end-stage renal disease treated with chronic hemodialysis (HD) are reported to have low levels of marine n-3 polyunsaturated fatty acids (PUFA) in plasma and cell membranes compared with healthy subjects. The aim of this study was to investigate whether n-3 PUFA levels in plasma and cells are lower in HD patients as compared with subjects without kidney disease. A comparative study was carried out. This study was carried out at the Departments of Nephrology and Cardiology, Aalborg Hospital, Aarhus University Hospital, Denmark. This study consisted of 2 study populations comprising HD patients and 5 study populations comprising subjects without kidney disease. The fatty acid distribution in plasma phospholipids and platelet phospholipids was measured using gas chromatography. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA) levels in plasma or serum phospholipids and platelet phospholipids in HD patients were compared with n-3 PUFA levels in subjects without kidney disease. EPA and DHA were lower and AA/EPA was higher in plasma/serum phospholipids in HD patients than in subjects without kidney disease. Similarly, higher AA and AA/EPA and lower EPA and DHA levels were found in platelet phospholipids of HD patients. Adjustment for gender, age, and habitual intake of fish and fish oil supplements did not change these results. HD patients have lower n-3 PUFA levels in plasma and cells compared with subjects without kidney disease. Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Composition of plasma and atheromatous plaque among coronary artery disease subjects consuming coconut oil or sunflower oil as the cooking medium.

PubMed

Palazhy, Sabitha; Kamath, Prakash; Rajesh, P C; Vaidyanathan, Kannan; Nair, Shiv K; Vasudevan, D M

2012-12-01

Coconut oil, which is rich in medium-chain saturated fatty acids, is the principal cooking medium of the people of Kerala, India. Replacement of saturated fat with polyunsaturated fat is effective in reducing serum cholesterol levels. However, the effect of substituting coconut oil with sunflower oil on the fatty acid composition of plaque has not been thoroughly investigated. We therefore evaluated and compared the fatty acid composition of plasma and plaque among subjects consuming coconut oil or sunflower oil as the cooking medium. Endarterectomy samples and plasma samples were obtained from subjects who underwent coronary artery bypass grafts (n = 71). The subjects were grouped based on the type of oil they were using as their cooking medium (coconut oil or sunflower oil). The fatty acid composition in the plaques and the plasma was determined by HPLC and the data were analyzed statistically. Sunflower oil consumers had elevated concentrations of linoleic acid (p = 0.001) in plasma, while coconut oil users had higher myristic acid levels (p = 0.011) in plasma. Medium-chain fatty acids did not differ significantly between the two groups in the plasma. Medium-chain fatty acids were detected in the plaques in both groups of subjects. In contrast to previous reports, long-chain saturated fatty acids dominated the lipid content of plaque in this population, and the fatty acid composition of plaque was not significantly different between the two groups. No correlation between fatty acids of plasma and plaque was observed in either group. A change in cooking medium, although it altered the plasma fatty acid composition, was not reflected in the plaque composition.

Plasma Levels of Folates, Riboflavin, Vitamin B6, and Ascorbate in Severely Disturbed Children.

ERIC Educational Resources Information Center

Sankar, D. V. Siva

1979-01-01

The plasma levels of folic acid, ascorbic acid, pyridoxine, and riboflavin were studied in 125 severely emotionally disturbed children (ages 5-16 years) to determine whether they had overt vitamin deficiencies. (Author/DLS)

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.

Plasma chemistry in booted eagle (Hieraaetus pennatus) during breeding season.

PubMed

Casado, Eva; Balbontin, Javier; Ferrer, Miguel

2002-02-01

Most studies that have examined raptor plasma chemistry have been conducted on birds living in captivity. In this study, we describe typical plasma chemistry values indicators of body condition in free-living Booted Eagles, Hieraaetus pennatus, from Doñana National Park (Spain). Values are compared with those of other raptors. Mean concentrations of creatinine, uric acid and urea were lower in adults than in nestlings, while glucose, DAT and AAT were lower in nestlings than in adults. Interactions of age/sex affected plasma mean levels of creatine kinase, glucose, AAT, uric acid and urea. Adult females showed significantly lower levels of creatine kinase, uric acid and urea than adult males and nestlings. Adult males had significantly higher levels of AAT than the other groups. The lowest levels of glucose and the highest levels of uric acid were found in nestling females. We think the differences in blood parameters can be explained by differences in size of species, of individuals (because of both body condition and sexual dimorphism) and diet.

Changes in plasma osmolality, cortisol and amino acid levels of tongue sole ( Cynoglossus semilaevis) at different salinities

NASA Astrophysics Data System (ADS)

Wang, Guodong; Xu, Kefeng; Tian, Xiangli; Dong, Shuanglin; Fang, Ziheng

2015-10-01

A serial of salinity transferring treatments were performed to investigate the osmoregulation of tongue sole ( Cynoglossus semilaevis). Juvenile tongue sole were directly transferred from a salinity of 30 to 0, 10, 20, 30, 40 and 50. Blood sampling was performed for each treatment after 0, 1, 6 and 12 h, as well as after 1, 2, 4, 8, 16 and 32 d. The plasma osmolality, cortisol and free amino acids were assessed. Under the experimental conditions, no fish died after acute salinity transfer. The plasma cortisol level increased 1 h after the abrupt transfer from a salinity of 30 to that of 0, 40 and 50, and decreased from 6 h to 8 d after transfer. Similar trends were observed in the changes of plasma osmolality. The plasma free amino acids concentration showed a `U-shaped' relationship with salinity after being transferred to different salinities for 4 days. More obvious changes of plasma free amino acid concentration occurred under hyper-osmotic conditions than under hypo-osmotic conditions. The concentrations of valine, isoleucine, lysine, glutamic acid, glycine, proline and taurine increased with rising salinity. The plasma levels of threonine, leucine, arginine, serine, and alanine showed a `U-shaped' relationship with salinity. The results of this study suggested that free amino acids might have important effects on osmotic acclimation in tongue sole.

Uric acid levels in plasma and urine in rats chronically exposed to inorganic As (III) and As(V).

PubMed

Jauge, P; Del-Razo, L M

1985-07-01

The effect of inorganic arsenic (III) and arsenic (V) on renal excretion and plasma levels of uric acid was examined in rats. Oral administration of 1200 micrograms As/kg/day for 6 weeks diminished uric acid levels in plasma by 67.1% and 26.5% of control after the administration of As(III) and As(V), respectively. Renal excretion of uric acid was significantly reduced during the first 3 weeks following As (III) administration, with a subsequent increase to approach control values at the end of the treatment. When As(V) was administered, the diminution in renal excretion was significant at 6 weeks.

Acculturation and plasma fatty acid concentrations in Hispanic and Chinese-American adults: The Multi-Ethnic Study of Atherosclerosis

USDA-ARS?s Scientific Manuscript database

Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may...

Some amino acids levels: glutamine,glutamate, and homocysteine, in plasma of children with chronic kidney disease.

PubMed

Fadel, Fatina I; Elshamaa, Manal F; Essam, Rascha G; Elghoroury, Eman A; El-Saeed, Gamila S M; El-Toukhy, Safinaz E; Ibrahim, Mona Hamed

2014-03-01

The high prevalence of protein-energy malnutrition is a critical issue for patients with chronic kidney disease (CKD). Serum albumin is the most commonly used nutritional marker. Another index is plasma amino acid (AA) profile. Of these, the plasma levels of glutamine, glutamate and homocysteine, correlate well with nutritional status. We measured some plasma AAs in children with different stages CKD to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. Three amino acids were evaluated along with albumin and high sensitivity C-reactive protein (hs-CRP) in 30 patients with advanced CKD stages 4 and 5. They were divided into two groups undergoing conservative treatment (CT) (n=15) or hemodialysis (HD) (n=15). An additional group of patients with nephrotic syndrome [CKD stage 2] was also studied to assess the alterations of plasma free amino acids with the early stage of CKD. Another 30 age- and sex-matched healthy children served as controls. A significant increase in plasma concentration of amino acid glutamine was observed in children with advanced CKD stages 4 and 5 when compared with controls (P=0.02).Plasma glutamine level was significantly higher in ESRD children on HD than in children with nephrotic syndrome (P=0.02). We did not find a significant difference between HD children and CT children as regard to glutamine level. Notable differences were in the plasma homocysteine level detected in the CKD groups patients, which was greater than that in controls (P=0.0001). Plasma homocysteine level was significantly higher in children on HD than in children with nephrotic syndrome (P=0.01). A significant differences was observed in hs-CRP levels between the CKD groups and the controls (P=0.04). Albumin levels were lower in CKD groups than in controls (p=0.01). Glutamine showed significant positive correlations with blood urea level (r=0.84, P=0.002) and blood ammonia level (r=0.72, P=0.0001). On multiple linear regression, urea was the only variable independently associated with an elevated plasma glutamine level (Beta=0.77, P=0.02). This study indicates that the advanced stages of CKD are associated with increased plasma concentrations of glutamine and homocysteine. Glutamine retained in the plasma of children with CRF, possibly producing higher levels of the waste products (urea and NH3). Dialysis alone is insufficient to redress completely the abnormalities in AA metabolism in ESRD children. Careful consideration of dialysis and dietary measures are necessary.

Nicotinamide pharmacokinetics in humans: effect of gastric acid inhibition, comparison of rectal vs oral administration and the use of saliva for drug monitoring.

PubMed Central

Stratford, M. R.; Dennis, M. F.; Hoskin, P.; Phillips, H.; Hodgkiss, R. J.; Rojas, A.

1996-01-01

The effect of inhibiting gastric acid secretion on nicotinamide pharmacokinetics was studied in five volunteers with the intent of reducing the large variations observed previously in the time to and magnitude of peak plasma concentrations. Plasma levels were determined using a standard high-performance liquid chromatography (HPLC) method after an oral dose of 3 g of nicotinamide either alone or preceded by pretreatment with omeprazole. Suppression of gastric acid production had no significant effect on the rate of uptake or on the peak levels achieved. To bypass gastric acidity, the rectal route was also assessed using a suppository in four volunteers and one patient undergoing radiotherapy. Absorption was slow and variable and much lower plasma levels were observed than after oral dosing. Thus, no improvement in the pharmacokinetics of nicotinamide was observed using either of these two approaches. Parallel estimations were made using a novel and non-invasive method for monitoring nicotinamide pharmacokinetics in saliva. A large and variable fraction of the total amount of nicotinamide-related material in saliva was found to be nicotinic acid, a metabolite not normally found in human plasma. This conversion was inhibited by the use of a chlorhexidine mouthwash, indicating that the oral flora was responsible for its production. The time to peak levels of nicotinamide or of nicotinamide plus nicotinic acid in saliva correlated well with that in plasma. However, peak concentrations for nicotinamide alone were significantly lower than in plasma, and very variable, whereas for nicotinamide plus nicotinic acid saliva levels were 20-30% higher, but more consistent. Although there are some practical difficulties in quantitatively handling saliva, the method is very useful for monitoring nicotinamide pharmacokinetics and for assessment of compliance with nicotinamide treatment. PMID:8679452

Breast milk provides better antioxidant power than does formula.

PubMed

Aycicek, Ali; Erel, Ozcan; Kocyigit, Abdurrahim; Selek, Sahbettin; Demirkol, Mehmet Resit

2006-06-01

We examined the effect of breast milk on plasma total antioxidant capacity (TAC), total peroxide (TP), and oxidative stress index (OSI), which are biomarkers of oxidative status. Fifty-four healthy term infants 3 to 6 mo of age were fed breast milk or a cow's milk modified formula. Plasma TAC, vitamin C, albumin, bilirubin, and uric acid levels were measured as indexes of antioxidative markers. Plasma TP levels were measured as an oxidative stress marker. The OSI was calculated to assess oxidative status. No significant differences were observed between groups with respect to growth or anthropometric measurements. Plasma uric acid, total protein, and albumin concentrations were slightly higher in the breast-fed group than in the formula-fed group. There was a positive correlation between infant's age and serum albumin levels; between TAC and plasma uric acid, albumin, and total bilirubin; and between plasma iron and TP levels in both groups (r > 0.256, P < 0.05). In addition, there was a negative correlation between plasma iron and TAC (r = -0.267, P = 0.01). Plasma TAC and vitamin C levels were significantly higher in the breast-fed group than in the formula-fed group (P < 0.05). Plasma TP levels and the OSI were higher in the formula-fed group than those in the breast-fed group (P < 0.05). Our data suggest that breast milk provides better antioxidant power than does formula.

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

Association between polymorphisms in the fatty acid desaturase gene cluster and the plasma triacylglycerol response to an n-3 PUFA supplementation.

PubMed

Cormier, Hubert; Rudkowska, Iwona; Paradis, Ann-Marie; Thifault, Elisabeth; Garneau, Véronique; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2012-08-01

Eicosapentaenoic and docosahexaenoic acids have been reported to have a variety of beneficial effects on cardiovascular disease risk factors. However, a large inter-individual variability in the plasma lipid response to an omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation is observed in different studies. Genetic variations may influence plasma lipid responsiveness. The aim of the present study was to examine the effects of a supplementation with n-3 PUFA on the plasma lipid profile in relation to the presence of single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster. A total of 208 subjects from Quebec City area were supplemented with 3 g/day of n-3 PUFA, during six weeks. In a statistical model including the effect of the genotype, the supplementation and the genotype by supplementation interaction, SNP rs174546 was significantly associated (p = 0.02) with plasma triglyceride (TG) levels, pre- and post-supplementation. The n-3 supplementation had an independent effect on plasma TG levels and no significant genotype by supplementation interaction effects were observed. In summary, our data support the notion that the FADS gene cluster is a major determinant of plasma TG levels. SNP rs174546 may be an important SNP associated with plasma TG levels and FADS1 gene expression independently of a nutritional intervention with n-3 PUFA.

Association between Polymorphisms in the Fatty Acid Desaturase Gene Cluster and the Plasma Triacylglycerol Response to an n-3 PUFA Supplementation

PubMed Central

Cormier, Hubert; Rudkowska, Iwona; Paradis, Ann-Marie; Thifault, Elisabeth; Garneau, Véronique; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2012-01-01

Eicosapentaenoic and docosahexaenoic acids have been reported to have a variety of beneficial effects on cardiovascular disease risk factors. However, a large inter-individual variability in the plasma lipid response to an omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation is observed in different studies. Genetic variations may influence plasma lipid responsiveness. The aim of the present study was to examine the effects of a supplementation with n-3 PUFA on the plasma lipid profile in relation to the presence of single-nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene cluster. A total of 208 subjects from Quebec City area were supplemented with 3 g/day of n-3 PUFA, during six weeks. In a statistical model including the effect of the genotype, the supplementation and the genotype by supplementation interaction, SNP rs174546 was significantly associated (p = 0.02) with plasma triglyceride (TG) levels, pre- and post-supplementation. The n-3 supplementation had an independent effect on plasma TG levels and no significant genotype by supplementation interaction effects were observed. In summary, our data support the notion that the FADS gene cluster is a major determinant of plasma TG levels. SNP rs174546 may be an important SNP associated with plasma TG levels and FADS1 gene expression independently of a nutritional intervention with n-3 PUFA. PMID:23016130

Activity of xanthine oxidase in plasma correlates with indices of insulin resistance and liver dysfunction in Japanese patients with type 2 diabetes mellitus and metabolic syndrome: A pilot exploratory study.

PubMed

Sunagawa, Sumito; Shirakura, Takashi; Hokama, Noboru; Kozuka, Chisayo; Yonamine, Masato; Namba, Toyotaka; Morishima, Satoko; Nakachi, Sawako; Nishi, Yukiko; Ikema, Tomomi; Okamoto, Shiki; Matsui, Chieko; Hase, Naoki; Tamura, Mizuho; Shimabukuro, Michio; Masuzaki, Hiroaki

2018-06-03

There is a controversy whether hyperuricemia is an independent risk for cardiometabolic diseases. Serum level of uric acid is affected by a wide variety of factors involved in its production and excretion. On the other hand, evidence has accumulated that locally and systemically activated xanthine oxidase (XO), a rate limiting enzyme for production of uric acid, is linked to metabolic derangement in humans and rodents. We therefore explored the clinical implication of plasma XO activity in patients with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). We enrolled 60 patients with T2DM and MetS. MetS was defined according to the 2005 International Diabetes Federation guidelines. Plasma XO activity was measured by highly sensitive fluorometric assay measuring the conversion of pterin to isoxanthopterin, and explored associations between the value of plasma XO activity and metabolic parameters. Value of plasma XO activity was correlated with indices of insulin resistance and level of circulating liver transaminases. On the other hand, level of serum uric acid was not correlated with indices of insulin resistance. The value of plasma XO activity was not correlated with serum uric acid level. Plasma XO activity correlates with indices of insulin resistance and liver dysfunction in Japanese patients with T2DM and MetS. Through assessing the plasma XO activity, patients demonstrating normal level of serum uric acid with higher activity of XO can be screened, thereby possibly providing a clue to uncover metabolic risks in T2DM and MetS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Weight loss is associated with plasma free amino acid alterations in subjects with metabolic syndrome

PubMed Central

Tochikubo, O; Nakamura, H; Jinzu, H; Nagao, K; Yoshida, H; Kageyama, N; Miyano, H

2016-01-01

Objectives: The prevalence of metabolic syndrome is increasing worldwide, especially in Asian populations. Early detection and effective intervention are vital. Plasma free amino acid profile is a potential biomarker for the early detection for lifestyle-related diseases. However, little is known about whether the altered plasma free amino acid profiles in subjects with metabolic syndrome are related to the effectiveness of dietary and exercise interventions. Methods: Eighty-five Japanese subjects who fulfilled the Japanese diagnostic criteria for metabolic syndrome were enrolled in a 3-month diet and exercise intervention. The plasma free amino acid concentrations and metabolic variables were measured, and the relationships between plasma free amino acid profiles, metabolic variables and the extent of body weight reduction were investigated. Those who lost more than 3% of body weight were compared with those who lost less than 3%. Results: Baseline levels of most amino acids in the subset that went on to lose <3% body weight were markedly lower compared with the counterpart, although both groups showed similar proportional pattern of plasma amino acid profiles. The weight loss induced by the diet and exercise intervention normalized plasma free amino acid profiles. For those with a high degree of weight loss, those changes were also associated with improvement in blood pressure, triglyceride and hemoglobin A1c levels. Conclusions: These data suggest that among Japanese adults meeting the criteria for metabolic syndrome, baseline plasma free amino acid profiles may differ in ways that predict who will be more vs less beneficially responsive to a standard diet and exercise program. Plasma free amino acid profiles may also be useful as markers for monitoring the risks of developing lifestyle-related diseases and measuring improvement in physiological states. PMID:26926588

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.

Selective enrichment of n-3 fatty acids in human plasma lipid motifs following intake of marine fish

USDA-ARS?s Scientific Manuscript database

Plasma levels of n-3 long chain polyunsaturated fatty acids (LCPUFA) are associated with a reduction in risk of cardiovascular disease and other chronic, age-related diseases like Alzheimer’s disease. In this work, we tested the hypothesis that n-3 LCPUFA fatty acids in human plasma are incorporated...

Distinct Plasma Profile of Polar Neutral Amino Acids, Leucine, and Glutamate in Children with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Tirouvanziam, Rabindra; Obukhanych, Tetyana V.; Laval, Julie; Aronov, Pavel A.; Libove, Robin; Banerjee, Arpita Goswami; Parker, Karen J.; O'Hara, Ruth; Herzenberg, Leonard A.; Herzenberg, Leonore A.; Hardan, Antonio Y.

2012-01-01

The goal of this investigation was to examine plasma amino acid (AA) levels in children with Autism Spectrum Disorders (ASD, N = 27) and neuro-typically developing controls (N = 20). We observed reduced plasma levels of most polar neutral AA and leucine in children with ASD. This AA profile conferred significant post hoc power for discriminating…

Contribution of the blood glucose level in perinatal asphyxia.

PubMed

Basu, Pallab; Som, Sabbasachi; Choudhuri, Nabendu; Das, Harendranath

2009-07-01

This is a comparative study between 60 asphyxiated newborns (cases) and 60 normal neonates (controls) in respect of their plasma glucose and uric acid levels and also their clinical and neurological status. The mean plasma glucose level was significantly lower (35.1 +/- 11.4 mg/dl vs. 56.9 +/- 5.5 mg/dl; P < 0.001) and the mean serum uric acid level was higher (8.0 +/- 1.2 mg/dl vs. 4.5 +/- 0.83 mg/dl; P < 0.001) in the asphyxiated group when compared to the controls. Within the perinatal asphyxia group, the plasma glucose level and Apgar scores showed a significant positive linear correlation (r = 0.740, P < 0.001), whereas a significant negative linear correlation was observed between the glucose level and different stages of hypoxic ischemic encephalopathy (HIE) (r = -0.875, P < 0.001). Although a strong positive linear correlation was found between uric acid and HIE stages (r = 0.734, P < or = 0.001), the linear correlation between uric acid and Apgar scores (r = -0.885, P < 0.001) and uric acid and the plasma glucose level (r = -0.725, P < 0.001) were found to be significantly negative among the cases. The severity of encephalopathy and cellular damage varies with the severity of hypoglycemia.

[The profile of plasma non-esterified fatty acids in children with different terms of type 1 diabetes mellitus].

PubMed

Akmurzina, V A; Petryairina, E E; Saveliev, S V; Selishcheva, A A

2016-01-01

Composition and quantitative content of non-esterified fatty acids (NEFA) were investigated in plasma samples of healthy children (12) and children with type 1 diabetes mellitus (DM1) (31) by gas chromatography (GC) after preliminary NEFA solid-phase extraction from plasma lipids. There was a significant (p<0.001) 1.6-fold increase in the total level of NEFA regardless of the disease duration. In the group of DM1 children with the disease period less than 1 year there was an increase in the arachidonic acid (20:4) content (30%) and the oleic acid trans-isomer (18:1) content (82%), and also a decrease in the docosahexaenoic acid (22:6 n3) content (26% ) and the docosapentaenoic acids (22:5 n-6) content (60%). In the group of DM1 children with prolonged course of this disease the altered NEFA levels returned to the normal level.

Occurrence of the free and Peptide forms of pyroglutamic acid in plasma from the portal blood of rats that had ingested a wheat gluten hydrolysate containing pyroglutamyl peptides.

PubMed

Higaki-Sato, Noriko; Sato, Kenji; Inoue, Naomi; Nawa, Yuko; Kido, Yasuhiro; Nakabou, Yukihiro; Hashimoto, Kaori; Nakamura, Yasushi; Ohtsuki, Kozo

2006-09-20

In order to determine pyroglutamic acid levels in plasma, we developed a method based on precolumn derivatization of the carboxyl group of pyroglutamic acid with 2-nitrophenylhydrazine. Eight-week-old male SD strain rats were administered 200 mg of an acidic peptide fraction obtained from a commercial wheat gluten hydrolysate containing 0.63 mmol/g pyroglutamyl peptide. After administration, significant amounts of free pyroglutamic acid were observed in the ethanol-soluble fraction of the plasma from the portal vein. In addition, pyroglutamate aminopeptidase digestion of the ethanol-soluble fraction liberated significant amounts of pyroglutamic acid, which indicated the presence of the pyroglutamyl peptide. The presence of the pyroglutamyl peptide in the plasma was further confirmed by size exclusion chromatography. The levels of free and peptide forms of pyroglutamic acid increased significantly and reached a maximum (approximately 40 nmol/mL) at 15 and 30 min after administration, respectively.

Influence of toll-like receptor 4 gene variants and plasma fatty acid profile on systemic inflammation: A population-based cross-sectional study.

PubMed

Norde, Marina Maintinguer; Oki, Erica; Carioca, Antonio A F; Castro, Inar A; Souza, José M P; Marchioni, Dirce M L; Fisberg, Regina M; Rogero, Marcelo M

2017-03-01

The aim of this study was to investigate the interaction of toll-like receptor 4 (TLR4) gene single nucleotide polymorphism (SNP) and plasma fatty acid (FA) profile in modulating risk for systemic inflammation. In all, 262 adult (19-59 y) participants of the Health Survey of São Paulo met the inclusion criteria. Anthropometric parameters, blood pressure, plasma inflammatory biomarker concentration, and fatty acid profile were measured and four SNPs of the TLR4 gene (rs4986790, rs4986791, rs11536889, and rs5030728) were genotyped. Multivariate cluster analysis was performed to stratify individuals based on levels of 11 plasma inflammatory biomarkers into two groups: inflammatory (INF) and noninflammatory (NINF). No association was found between any of the SNPs studied and systemic inflammation. The INF cluster had higher palmitic acid levels (P = 0.039) and estimated stearoyl coenzyme A desaturase activity (P = 0.045) and lower polyunsaturated fatty acid (P = 0.011), ω-6 fatty acid (P = 0.018), arachidonic acid (P = 0.002) levels, and estimated δ-5 desaturase activity (P = 0.025) compared with the NINF cluster. Statistically significant interaction between rs11536889 and arachidonic acid/eicosapentaenoic acid (AA/EPA) ratio (P = 0.034) was found to increase the odds of belonging to the INF cluster when individuals had the variant allele C and were at the higher percentile of AA/EPA plasma ratio. Plasma fatty acid profile modulated the odds of belonging to the INF cluster depending on genotypes of TRL4 gene polymorphisms. Copyright © 2016 Elsevier Inc. All rights reserved.

High Protein Intake Does Not Prevent Low Plasma Levels of Conditionally Essential Amino Acids in Very Preterm Infants Receiving Parenteral Nutrition.

PubMed

Morgan, Colin; Burgess, Laura

2017-03-01

We have shown that increasing protein intake using a standardized, concentrated, added macronutrients parenteral (SCAMP) nutrition regimen improves head growth in very preterm infants (VPIs) compared with a control parenteral nutrition (PN) regimen. VPIs are at risk of conditionally essential amino acid (CEAA) deficiencies because of current neonatal PN amino acid (AA) formulations. We hypothesized that the SCAMP regimen would prevent low plasma levels of CEAAs. To compare the plasma AA profiles at approximately day 9 of life in VPIs receiving SCAMP vs a control PN regimen. VPIs (<29 weeks' gestation) were randomized to receive SCAMP (30% more PN AA) or a control regimen. Data were collected to measure parenteral and enteral protein, energy, and individual AA intake and the first plasma AA profile. Plasma profiles of the 20 individual protogenic AA levels were measured using ion exchange chromatography. Plasma AA profiles were obtained at median (interquartile range [IQR]) age of 9 (8-10) days in both SCAMP (n = 59) and control (n = 67) groups after randomizing 150 VPIs. Median (IQR) plasma levels of individual essential AAs were higher than the reference population mean (RPM) in both groups, especially for threonine. SCAMP infants had higher plasma levels of essential AAs than did the controls. Median (IQR) plasma levels of glutamine, arginine, and cysteine (CEAAs) were lower than the RPM in both groups. Plasma AA levels in PN-dependent VPIs indicate there is an imbalance in essential and CEAA provision in neonatal PN AA formulations that is not improved by increasing protein intake.

Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment

PubMed Central

Saunders, Erika FH; Reider, Aubrey; Singh, Gagan; Gelenberg, Alan J; Rapoport, Stanley I

2015-01-01

Objectives Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFA) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFA would be lower and of n-6 PUFA higher in subjects with bipolar disorder (BD) compared to healthy controls (HC), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. Methods This observational, parallel group study compared biomarkers between HC (n = 31), and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFA [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], of two saturated fatty acids (palmitic acid and stearic acid) and of two monounsaturated fatty acids (palmitoleic acid, oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFA, ratios of n-3 PUFA (DHA:ALA, EPA:ALA, EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using Chi-square tests. Pearson’s r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. Results UE EPA was lower in BD than HC, with a large effect size (Cohen’s d = 0.86, p < 0.002), however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between BD and HC after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in BD than HC (p < 0.0001). At follow-up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported n-3 PUFA intake or use of medication by class. Conclusions A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be an important factor in vulnerability to a mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n-3 and decrease n-6 dietary PUFA intake. PMID:26424416

Fish oil and krill oil supplementations differentially regulate lipid catabolic and synthetic pathways in mice

PubMed Central

2014-01-01

Background Marine derived oils are rich in long-chain polyunsaturated omega-3 fatty acids, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have long been associated with health promoting effects such as reduced plasma lipid levels and anti-inflammatory effects. Krill oil (KO) is a novel marine oil on the market and is also rich in EPA and DHA, but the fatty acids are incorporated mainly into phospholipids (PLs) rather than triacylglycerols (TAG). This study compares the effects of fish oil (FO) and KO on gene regulation that influences plasma and liver lipids in a high fat diet mouse model. Methods Male C57BL/6J mice were fed either a high-fat diet (HF) containing 24% (wt/wt) fat (21.3% lard and 2.3% soy oil), or the HF diet supplemented with FO (15.7% lard, 2.3% soy oil and 5.8% FO) or KO (15.6% lard, 2.3% soy oil and 5.7% KO) for 6 weeks. Total levels of cholesterol, TAG, PLs, and fatty acid composition were measured in plasma and liver. Gene regulation was investigated using quantitative PCR in liver and intestinal epithelium. Results Plasma cholesterol (esterified and unesterified), TAG and PLs were significantly decreased with FO. Analysis of the plasma lipoprotein particles indicated that the lipid lowering effect by FO is at least in part due to decreased very low density lipoprotein (VLDL) content in plasma with subsequent liver lipid accumulation. KO lowered plasma non-esterified fatty acids (NEFA) with a minor effect on fatty acid accumulation in the liver. In spite of a lower omega-3 fatty acid content in the KO supplemented diet, plasma and liver PLs omega-3 levels were similar in the two groups, indicating a higher bioavailability of omega-3 fatty acids from KO. KO more efficiently decreased arachidonic acid and its elongation/desaturation products in plasma and liver. FO mainly increased the expression of several genes involved in fatty acid metabolism, while KO specifically decreased the expression of genes involved in the early steps of isoprenoid/cholesterol and lipid synthesis. Conclusions The data show that both FO and KO promote lowering of plasma lipids and regulate lipid homeostasis, but with different efficiency and partially via different mechanisms. PMID:24834104

Supplementation of arachidonic acid rich oil in European sea bass juveniles (Dicentrarchus labrax) diets: Effects on leucocytes and plasma fatty acid profiles, selected immune parameters and circulating prostaglandins levels.

PubMed

Torrecillas, S; Román, L; Rivero-Ramírez, F; Caballero, M J; Pascual, C; Robaina, L; Izquierdo, M S; Acosta, F; Montero, D

2017-05-01

The main objective of this study was to assess the effects of graded levels of dietary arachidonic acid (ARA), supplemented from alternative sources, on fatty acid composition of plasma and head kidney leucocytes of European sea bass (Dicentrarchus labrax). For that purpose, sea bass juveniles were fed four diets containing graded levels of ARA as follows: 0.5% (ARA0.5), 1% (ARA1), 2% (ARA2) and 4% (ARA4) during 60 days. At the end of the feeding trial fatty acid profiles of plasma and head kidney leucocytes were analyzed. Besides, plasma prostaglandins levels, head kidney leucocytes respiratory burst activity; peroxidase activity and phagocytic index were assayed. Reducing dietary ARA levels below 1% markedly reduced European sea bass growth performance. However, fish fed diet ARA0.5 tried to compensate this dietary ARA deficiency by a selective deposition of ARA on plasma and head kidney leucocytes, reaching similar levels to those fish fed diet ARA1 after 60 days of feeding. Nevertheless, head kidney phagocytic capacity was reduced as dietary ARA content in relation not only to variations on membrane composition but also to changes on fish basal prostaglandins levels. Results obtained demonstrated the importance to supply the necessary quantity n-6 LC-PUFA, and not only n-3 LC-PUFA levels, in European sea bass diets, in relation to not only growth performance but also immune system function. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of dairy fat on plasma phytanic acid in healthy volunteers - a randomized controlled study

PubMed Central

2011-01-01

Background Phytanic acid produced in ruminants from chlorophyll may have preventive effects on the metabolic syndrome, partly due to its reported RXR and PPAR- α agonist activity. Milk from cows fed increased levels of green plant material, contains increased phytanic acid concentrations, but it is unknown to what extent minor increases in phytanic acid content in dairy fat leads to higher circulating levels of phytanic acid in plasma of the consumers. Objective To investigate if cow feeding regimes affects concentration of plasma phytanic acid and risk markers of the metabolic syndrome in human. Design In a double-blind, randomized, 4 wk, parallel intervention study 14 healthy young subjects were given 45 g milk fat/d from test butter and cheese with 0.24 wt% phytanic acid or a control diet with 0.13 wt% phytanic acid. Difference in phytanic acid was obtained by feeding roughage with low or high content of chlorophyll. Results There tended to be a difference in plasma phytanic acid (P = 0.0730) concentration after the dietary intervention. Plasma phytanic acid increased significantly within both groups with the highest increase in control group (24%) compared to phytanic acid group (15%). There were no significant effects of phytanic acid on risk markers for the metabolic syndrome. Conclusions The results indicate that increased intake of dairy fat modify the plasma phytanic acid concentration, regardless of cows feeding regime and the minor difference in dietary phytanic acid. Whether the phytanic acid has potential to affects the risk markers of the metabolic syndrome in human still remain to be elucidated. Trial Registration ClinicalTrials.gov: NCT01343576 PMID:21663648

Effect of chronic diuretic treatment on the plasma renin-angiotensin-aldosterone system in essential hypertension.

PubMed Central

Lijnen, P; Fagard, R; Staessen, J; Amery, A

1981-01-01

1 Chronic treatment with a constant dose of hydrochlorothiazide or tienilic acid increases plasma renin activity (PRA) acutely to reach a maximum within the first week. 2 During chronic diuretic therapy from 1 month to 1 year, PRA remained elevated at a rather constant level, though this was somewhat lower than the maximum level reached after 1 week. 3 A significant (P less than 0.01) correlation (r = 0.74) between changes in plasma angiotensin II and renin activity provoked by chronic treatment for 3 months with hydrochlorothiazide and tienilic acid was found. 4 The increase in plasma aldosterone during chronic treatment with hydrochlorothiazide and tienilic acid (1000 mg) is related (r = 0.68; P less than 0.01) to the rise in plasma angiotensin II. PMID:7028060

Effect of Maillard browning reaction on protein utilization and plasma amino acid response by rainbow trout (Salmo gairdneri).

PubMed

Plakas, S M; Lee, T C; Wolke, R E; Meade, T L

1985-12-01

The effect of the Maillard browning reaction in the diet of rainbow trout (Salmo gairdneri) on growth and amino acid availability was investigated. Chemical and enzymatic hydrolysis methods were applied for the detection of the losses of amino acids in a model protein browning system. Arginine and lysine exhibited the greatest losses in the mixture of fish protein isolate and glucose stored for 40 d at 37 degrees C. The apparent digestibility and absorption of individual amino acids, particularly lysine, was lower in trout fed browned protein than in those fed the control protein. Plasma lysine levels were significantly depressed, while the plasma levels of glucose and most other amino acids were elevated in relation to the loss in nutritive value of dietary protein after browning. The early Maillard reaction derivative of lysine, epsilon-deoxy-fructosyl-lysine, was recovered from browned protein (by using the in vitro enzymatic hydrolysis procedure) and from the plasma of trout fed browned protein. Analysis of plasma free amino acids provided an indication of lysine bioavailability and identified lysine as the first-limiting amino acid in the diets containing browned protein.

Relation of soya bean meal level to the concentration of plasma free amino acids and body growth in white rats.

PubMed

Mandal, Tapas K; Parvin, Nargish; Mondal, Santanu; Saxena, Vijaylaxmi; Saxena, Ashok K; Sarkar, Sabyasachi; Saha, Mitali

2012-04-01

Amino acid (AA) levels in plasma and body growth were determined in rats (n20) fed diets with different soya bean meal levels. Free AA in plasma was determined by reversed-phase high-pressure liquid chromatography. We have used four levels of protein diets like 8%, 15%, 23% and 35% in this trial. Rats which were fed the low-protein (8%) diet with low percentage of soya bean meal were found to be growth-retarded. The body weight gain of high protein group (35%) was lower than that of the 23% groups. In the rats fed with the low-soya bean meal diet, some nonessential AA (NEAA) in plasma like asparagine, aspartic acid, cysteine, glutamic acid and serine increased, whereas the essential AA (EAA), with the exception of arginine, methionine and valine decreased. Here, plasma EAA-to-NEAA ratios were not correlated to growth and experimental diet. We hypothesize that AA metabolism is associated to changes in growth in rats on different protein intake. This study has showed the sensitivity of body mass gain, feed intake, feed conversion rate of rats to four levels of protein in the diet under controlled experimental conditions. © 2011 Blackwell Verlag GmbH.

Effect of dietary n-3 fatty acids supplementation on fatty acid metabolism in atorvastatin-administered SHR.Cg-Leprcp/NDmcr rats, a metabolic syndrome model.

PubMed

Al Mamun, Abdullah; Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Tsuchikura, Satoru; Hossain, Shahdat; Shido, Osamu

2017-01-01

The effects of cholesterol-lowering statins, which substantially benefit future cardiovascular events, on fatty acid metabolism have remained largely obscured. In this study, we investigated the effects of atorvastatin on fatty acid metabolism together with the effects of TAK-085 containing highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) ethyl ester on atorvastatin-induced n-3 polyunsaturated fatty acid lowering in SHR.Cg-Lepr cp /NDmcr (SHRcp) rats, as a metabolic syndrome model. Supplementation with 10mg/kg body weight/day of atorvastatin for 17 weeks significantly decreased plasma total cholesterol and very low density lipoprotein cholesterol. Atorvastatin alone caused a subtle change in fatty acid composition particularly of EPA and DHA in the plasma, liver or erythrocyte membranes. However, the TAK-085 consistently increased both the levels of EPA and DHA in the plasma, liver and erythrocyte membranes. After confirming the reduction of plasma total cholesterol, 300mg/kg body weight/day of TAK-085 was continuously administered for another 6 weeks. Supplementation with TAK-085 did not decrease plasma total cholesterol but significantly increased the EPA and DHA levels in both the plasma and liver compared with rats administered atorvastatin only. Supplementation with atorvastatin alone significantly decreased sterol regulatory element-binding protein-1c, Δ5- and Δ6-desaturases, elongase-5, and stearoyl-coenzyme A (CoA) desaturase-2 levels and increased 3-hydroxy-3-methylglutaryl-CoA reductase mRNA expression in the liver compared with control rats. TAK-085 supplementation significantly increased stearoyl-CoA desaturase-2 mRNA expression. These results suggest that long-term supplementation with atorvastatin decreases the EPA and DHA levels by inhibiting the desaturation and elongation of n-3 fatty acid metabolism, while TAK-085 supplementation effectively replenishes this effect in SHRcp rat liver. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Interactive effects of naphthalene treatment and the onset of vitellogenesis on energy metabolism in liver and gonad, and plasma steroid hormones of rainbow trout Oncorhynchus mykiss.

PubMed

Tintos, Adrián; Gesto, Manuel; Alvarez, Rosa; Míguez, Jesús M; Soengas, José L

2006-10-01

The purpose of the study was to assess in female fish the possible interaction between treatment with a polycyclic aromatic hydrocarbon (PAH) like naphthalene and the onset of vitellogenesis. In a first experiment, female rainbow trout (Oncorhynchus mykiss) at stages 2-3 (previtellogenesis) or 4 (early vitellogenesis) were intraperitoneally injected (2 microl g(-1)) with vegetable oil alone (control) or containing naphthalene (50 mg kg(-1)) to be sampled 3 h later. A second experiment was similarly designed but using fish intraperitoneally implanted (10 microl g(-1)) with slow-release coconut oil implants alone (control) or containing 50 mg naphthalene kg(-1) body mass that were sampled 3 days after injection. On each sampling time, plasma levels of cortisol and 17beta-estradiol, and several metabolic parameters in plasma, liver and gonad were assessed. In controls, early vitellogenic fish compared with previtellogenic fish displayed changes that in some cases are confirmatory of previous studies whereas in other cases provide new information in plasma (increased amino acid levels), liver (decreased capacity for exporting glucose and reduced amino acid levels) and gonad (decreased amino acid levels). Naphthalene treatment produced in previtellogenic fish decreased 17beta-estradiol levels in plasma, increased plasma glucose or decreased liver gluconeogenic capacity whereas no major effects were noticed on parameters involved in lipid, amino acid and lactate metabolism. Differential effects of naphthalene treatment were noticed in early vitellogenic fish such as decreased 17beta-estradiol and glucose levels in plasma, increased hexokinase and glucokinase and lack of changes in fructose 1,6-bisphosphatase activities in liver, and a lower decrease of amino acid levels in gonad. Those alterations produced by naphthalene treatment resulted in a decreased capacity for covering the energy demand of vitellogenesis in liver and gonad that could contribute to a delay and/or impairment of the onset of maturation.

Effect of 2-(4-aminophenylmethyl)-6-hydroxy-3, 4-dihydronaphthalen-1(2H)-one on all-trans and 13-cis-retinoic acid levels in plasma quantified by high perfomance liquid chromatography coupled to tandem mass spectrometry.

PubMed

Angotti, Marc; Hartmann, Rolf W; Kirby, Andrew J; Simons, Claire; Nicholls, Paul J; Sewell, Robert D E; Smith, H John

2005-06-01

The effect of the titled tetralone as a retinoic acid metabolism blocking agent (RAMBA) in vivo in comparison with ketoconazole, a well known cytochrome P450 inhibitor, was studied. Development of a HPLC/MS/MS method for the quantification of retinoic acid levels extracted from rat plasma was used to demonstrate that ketoconazole and the tetralone (100 mg/kg) enhanced the endogenous plasma concentration of retinoic acid. Levels of retinoid were raised from a control value of 0.11 to 0.15 and 0.17 ng/mL after treatment with tetralone and ketoconazole respectively showing that the tetralone and ketoconazole lead to comparable effects, indicating an inhibitory activity of the tetralone on retinoic acid metabolism.

Determination of GABA and vigabatrin in human plasma by a rapid and simple HPLC method: correlation between clinical response to vigabatrin and increase in plasma GABA.

PubMed

Löscher, W; Fassbender, C P; Gram, L; Gramer, M; Hörstermann, D; Zahner, B; Stefan, H

1993-03-01

The novel antiepileptic drug vigabatrin (Sabril) acts by inhibiting degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), increasing the GABA concentrations in the brain. Because the GABA degrading enzyme GABA aminotransferase (GABA-T) is also present in peripheral tissues, including blood platelets, measurement of plasma GABA levels might be a useful indication of the pharmacological response to vigabatrin during therapeutic monitoring. However, because of the very low concentrations of GABA in plasma, the few methods available for plasma GABA analysis are time-consuming, difficult to perform and/or not selective enough because of potential interference with other plasma constituents. In the present study, a rapid, selective and sensitive amino acid analysis HPLC method has been developed for plasma GABA determination with fluorescence detection, using o-phthaldialdehyde as a precolumn derivatizing agent. By employing a 3 microns particle size reversed-phase column and a multi-step gradient system of two solvents, the very low endogenous concentration of GABA in human plasma could be reproducibly quantitated without interference of other endogenous compounds. Incubation of human plasma samples with GABA degrading enzyme(s) resulted in an almost total loss of the GABA peak, thus demonstrating the specificity of the method for GABA analysis. In addition to GABA and other endogenous amino acids, the HPLC method could be used to quantitate plasma levels of vigabatrin. Thus, this improved HPLC amino acid assay might be used to examine whether concomitant monitoring of plasma GABA and vigabatrin is useful for clinical purposes. This was examined in 20 epileptic patients undergoing chronic treatment with vigabatrin. The average plasma GABA level of these 20 patients did not differ significantly from non-epileptic controls. However, when epileptic patients were subdivided according to their clinical response to vigabatrin, vigabatrin responders had significantly higher GABA levels than nonresponders or controls. In contrast to the difference in plasma GABA, vigabatrin responders and nonresponders did not differ in dose or plasma level of vigabatrin. These data may indicate that determination of plasma GABA is a valuable non-invasive method for therapeutic monitoring in patients on medication with vigabatrin.

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men

PubMed Central

Nakayama, Kyosuke; Sanbongi, Chiaki; Ikegami, Shuji

2018-01-01

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12–15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally. PMID:29671767

Effects of Whey Protein Hydrolysate Ingestion on Postprandial Aminoacidemia Compared with a Free Amino Acid Mixture in Young Men.

PubMed

Nakayama, Kyosuke; Sanbongi, Chiaki; Ikegami, Shuji

2018-04-19

To stimulate muscle protein synthesis, it is important to increase the plasma levels of essential amino acids (EAA), especially leucine, by ingesting proteins. Protein hydrolysate ingestion can induce postprandial hyperaminoacidemia; however, it is unclear whether protein hydrolysate is associated with higher levels of aminoacidemia compared with a free amino acid mixture when both are ingested orally. We assessed the effects of whey protein hydrolysate (WPH) ingestion on postprandial aminoacidemia, especially plasma leucine levels, compared to ingestion of a free amino acid mixture. This study was an open-label, randomized, 4 × 4 Latin square design. After 12⁻15 h of fasting, 11 healthy young men ingested the WPH (3.3, 5.0, or 7.5 g of protein) or the EAA mixture (2.5 g). Blood samples were collected before ingestion and at time points from 10 to 120 min after ingestion, and amino acids, insulin, glucose and insulin-like growth factor-1 (IGF-1) concentrations in plasma were measured. Even though the EAA mixture and 5.0 g of the WPH contained similar amounts of EAA and leucine, the WPH was associated with significantly higher plasma EAA and leucine levels. These results suggest that the WPH can induce a higher level of aminoacidemia compared with a free amino acid mixture when both are ingested orally.

Changes in plasma phenylalanine, isoleucine, leucine, and valine are associated with significant changes in intracranial pressure and jugular venous oxygen saturation in patients with severe traumatic brain injury.

PubMed

Vuille-Dit-Bille, Raphael N; Ha-Huy, Riem; Stover, John F

2012-09-01

Changes in plasma aromatic amino acids (AAA = phenylalanine, tryptophan, tyrosine) and branched chain amino acids (BCAA = isoleucine, leucine, valine) levels possibly influencing intracranial pressure (ICP) and cerebral oxygen consumption (SjvO(2)) were investigated in 19 sedated patients up to 14 days following severe traumatic brain injury (TBI). Compared to 44 healthy volunteers, jugular venous plasma BCAA were significantly decreased by 35% (p < 0.001) while AAA were markedly increased in TBI patients by 19% (p < 0.001). The BCAA to AAA ratio was significantly decreased by 55% (p < 0.001) which persisted during the entire study period. Elevated plasma phenylalanine was associated with decreased ICP and increased SjvO(2), while higher plasma isoleucine and leucine levels were associated with increased ICP and higher plasma leucine and valine were linked to decreased SjvO(2). The amount of enterally administered amino acids was associated with significantly increased plasma levels with the exception of phenylalanine. Contrary to the initial assumption that elevated AAA and decreased BCAA levels are detrimental, increased plasma phenylalanine levels were associated with beneficial signs in terms of decreased ICP and reduced cerebral oxygen consumption reflected by increased SjvO(2); concomitantly, elevated plasma isoleucine and leucine levels were associated with increased ICP while leucine and valine were associated with decreased SjvO(2) following severe TBI, respectively. The impact of enteral nutrition on this observed pattern must be examined prospectively to determine if higher amounts of phenylalanine should be administered to promote beneficial effects on brain metabolism and if normalization of plasma BCAA levels is without cerebral side effects.

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

PubMed

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

2016-09-01

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

Omega-3 fatty acids are inversely related to callous and unemotional traits in adolescent boys with attention deficit hyperactivity disorder.

PubMed

Gow, Rachel V; Vallee-Tourangeau, Frederic; Crawford, Michael Angus; Taylor, Eric; Ghebremeskel, Kebreab; Bueno, Allain A; Hibbeln, Joseph R; Sumich, Alexander; Rubia, Katya

2013-06-01

A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n-3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n=29) and without a clinical diagnosis of ADHD (n=43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous-unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels. Copyright © 2013 Elsevier Ltd. All rights reserved.

Low unesterified:esterified eicosapentaenoic acid (EPA) plasma concentration ratio is associated with bipolar disorder episodes, and omega-3 plasma concentrations are altered by treatment.

PubMed

Saunders, Erika Fh; Reider, Aubrey; Singh, Gagan; Gelenberg, Alan J; Rapoport, Stanley I

2015-11-01

Omega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids. This observational, parallel group study compared biomarkers between HCs (n = 31) and symptomatic subjects with BD (n = 27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, and between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using chi-square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis. UE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d = 0.86, p < 0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p < 0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p < 0.0001). At follow-up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p < 0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported n-3 PUFA intake or use of medication by class. A large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n-3 and decrease n-6 dietary PUFA intake. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Investigation into the plasma concentration of ω3 polyunsaturated fatty acids in Japanese attention-deficit hyperactivity disorder patients.

PubMed

Yonezawa, Ken; Nonaka, Shunsuke; Iwakura, Yuka; Kusano, Yuka; Funamoto, Yuko; Kanchi, Nobukazu; Yamaguchi, Naohiro; Kusumoto, Yuko; Imamura, Akira; Ozawa, Hiroki

2018-06-20

Several studies report that patients with attention-deficit hyperactivity disorder (ADHD) have a low plasma concentration of polyunsaturated fatty acids (PUFAs). Since fish intake varies among countries and is high in Japan, those results may not apply to Japanese patients with ADHD. However, there is currently not enough evidence to support this. We compared the plasma PUFAs levels of patients with ADHD with the standard reference levels for healthy subjects, and examined the relationship between those PUFAs levels and the subject's psychological evaluation. The subjects were 24 patients (age < 20 years) previously diagnosed with ADHD (according to the DSM-IV-TR criteria) at the psychiatric department of the Nagasaki University Hospital, between November 2010 and November 2015. The plasma concentrations of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) were measured using gas chromatography. Data pertaining to global assessment of functioning (GAF), clinical global impressions, ADHD Rating Scale-IV, and the drug used for treatment (atomoxetine or methylphenidate) were obtained from the medical records. The plasma concentrations of DHA, EPA, and EPA/AA were significantly lower than the normal reference range, indicating that ADHD patients present an imbalance in PUFAs levels. This trend is similar to ADHD patients in other countries and replacement therapy in Japanese ADHD patients may be useful.

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease.

PubMed

Blindauer, Claudia A; Khazaipoul, Siavash; Yu, Ruitao; Stewart, Alan J

2016-01-01

Human serum albumin (HSA) is the major protein in blood plasma and is responsible for circulatory transport of a range of small molecules including fatty acids, metal ions and drugs. We previously identified the major plasma Zn2+ transport site on HSA and revealed that fatty-acid binding (at a distinct site called the FA2 site) and Zn2+ binding are interdependent via an allosteric mechanism. Since binding affinities of long-chain fatty acids exceed those of plasma Zn2+, this means that under certain circumstances the binding of fatty acid molecules to HSA is likely to diminish HSA Zn2+-binding, and hence affects the control of circulatory and cellular Zn2+ dynamics. This relationship between circulatory fatty acid and Zn2+ dynamics is likely to have important physiological and pathological implications, especially since it has been recognised that Zn2+ acts as a signalling agent in many cell types. Fatty acid levels in the blood are dynamic, but most importantly, chronic elevation of plasma fatty acid levels is associated with some metabolic disorders and disease states - including myocardial infarction and other cardiovascular diseases. In this article, we briefly review the metal-binding properties of albumin and highlight the importance of their interplay with fatty acid binding. We also consider the impact of this dynamic link upon levels and speciation of plasma Zn2+, its effect upon cellular Zn2+ homeostasis and its relevance to cardiovascular and circulatory processes in health and disease.

Docosapentaenoic acid and docosahexaenoic acid are positively associated with insulin sensitivity in rats fed high-fat and high-fructose diets.

PubMed

Huang, Jiung-Pang; Cheng, Mei-Ling; Hung, Cheng-Yu; Wang, Chao-Hung; Hsieh, Po-Shiuan; Shiao, Ming-Shi; Chen, Jan-Kan; Li, Dai-Er; Hung, Li-Man

2017-10-01

The aim of the present study was to compare insulin resistance and metabolic changes using a global lipidomic approach. Rats were fed a high-fat diet (HFD) or a high-fructose diet (HFrD) for 12 weeks to induce insulin resistance (IR) syndrome. After 12 weeks feeding, physiological and biochemical parameters were examined. Insulin sensitivity and plasma metabolites were evaluated using a euglycemic-hyperinsulinemic clamp and mass spectrometry, respectively. Pearson's correlation coefficient was used to investigate the strength of correlations. Rats on both diets developed IR syndrome, characterized by hypertension, hyperlipidemia, hyperinsulinemia, impaired fasting glucose, and IR. Compared with HFrD-fed rats, non-esterified fatty acids were lower and body weight and plasma insulin levels were markedly higher in HFD-fed rats. Adiposity and plasma leptin levels were increased in both groups. However, the size of adipocytes was greater in HFD- than HFrD-fed rats. Notably, the lipidomic heat map revealed metabolites exhibiting greater differences in HFD- and HFrD-fed rats compared with controls. Plasma adrenic acid levels were higher in HFD- than HFrD-fed rats. Nevertheless, linoleic and arachidonic acid levels decreased in HFrD-fed rats compared with controls. Plasma concentrations of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) were significantly reduced after feeding of both diets, particularly the HFrD. There was a strong positive correlation between these two fatty acids and the insulin sensitivity index. The systemic lipidomic analysis indicated that a reduction in DHA and DPA was strongly correlated with IR in rats under long-term overnutrition. These results provide a potential therapeutic target for IR and metabolic syndrome. © 2016 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

On the suppression of plasma nonesterified fatty acids by insulin during enhanced intravascular lipolysis in humans.

PubMed

Carpentier, André C; Frisch, Frédérique; Cyr, Denis; Généreux, Philippe; Patterson, Bruce W; Giguère, Robert; Baillargeon, Jean-Patrice

2005-11-01

During the fasting state, insulin reduces nonesterified fatty acid (NEFA) appearance in the systemic circulation mostly by suppressing intracellular lipolysis in the adipose tissue. In the postprandial state, insulin may also control NEFA appearance through enhanced trapping into the adipose tissue of NEFA derived from intravascular triglyceride lipolysis. To determine the contribution of suppression of intracellular lipolysis in the modulation of plasma NEFA metabolism by insulin during enhanced intravascular triglyceride lipolysis, 10 healthy nonobese subjects underwent pancreatic clamps at fasting vs. high physiological insulin level with intravenous infusion of heparin plus Intralipid. Nicotinic acid was administered orally during the last 2 h of each 4-h clamp to inhibit intracellular lipolysis and assess insulin's effect on plasma NEFA metabolism independently of its effect on intracellular lipolysis. Stable isotope tracers of palmitate, acetate, and glycerol were used to assess plasma NEFA metabolism and total triglyceride lipolysis in each participant. The glycerol appearance rate was similar during fasting vs. high insulin level, but plasma NEFA levels were significantly lowered by insulin. Nicotinic acid significantly blunted the insulin-mediated suppression of plasma palmitate appearance and oxidation rates by approximately 60 and approximately 70%, respectively. In contrast, nicotinic acid did not affect the marked stimulation of palmitate clearance by insulin. Thus most of the insulin-mediated reduction of plasma NEFA appearance and oxidation can be explained by suppression of intracellular lipolysis during enhanced intravascular triglyceride lipolysis in healthy humans. Our results also suggest that insulin may affect plasma NEFA clearance independently of the suppression of intracellular lipolysis.

Effect of omega 3 and omega 6 fatty acid intakes from diet and supplements on plasma fatty acid levels in the first 3 years of life.

PubMed

Hoyos, Camilla; Almqvist, Catarina; Garden, Frances; Xuan, Wei; Oddy, Wendy H; Marks, Guy B; Webb, Karen L

2008-01-01

The optimal method for conducting omega (n-)3 polyunsaturated fatty acid (PUFA) supplementation trials in children is unknown. To assess the impact of n-3 and n-6 PUFA intake from the background diet on plasma levels of n-3 and n-6 PUFA in children aged 0-3 years, with and without n-3 supplementation. Subjects were randomised antenatally to receive either n-3 PUFA supplements and low n-6 PUFA cooking oils and spreads or a control intervention, designed to maintain usual fatty acid intake. Dietary intake was assessed at 18 months by 3-day weighed food record and at 3 years by food frequency questionnaire. Plasma phospholipids were measured at both time points. Associations were tested by regression. N-3 PUFA intake from background diet did not significantly affect plasma n-3 levels. In contrast, n-6 PUFA intake in background diet was positively related to plasma n-6 levels in both study groups. In addition, n-6 PUFA intake from diet was negatively associated with plasma n-3 levels at 18 months and 3 years (-0.16%/g n-6 intake, 95%CI -0.29 to -0.03 and -0.05%/g n-6 intake, 95%CI -0.09 to -0.01, respectively) in the active group, but not in the control group. Interventions intending to increase plasma n-3 PUFA in children by n-3 supplementation should also minimise n-6 PUFA intake in the background diet.

Albumin dialysis has a favorable effect on amino acid profile in hepatic encephalopathy.

PubMed

Koivusalo, Anna-Maria; Teikari, Taru; Höckerstedt, Krister; Isoniemi, Helena

2008-12-01

According to one popular theory, hepatic encephalopathy (HE) is partly caused by an imbalance in plasma amino acid levels. The Fischer's ratio between branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) correlates with the degree of HE; the lower Fischer's ratio, the higher the grade of HE. Extra-corporeal liver support systems, like MARS(R)-albumin dialysis (Molecular Adsorbents Recirculating System), can improve HE. The MARS(R) system uses a hyperosmolar albumin circuit to remove both water-soluble and albumin-bound substances. Plasma levels of neuroactive amino acids were analyzed in 82 consecutive patients with life-threatening liver failure admitted to our ICU. All patients fulfilled our indications for MARS treatment and most also fulfilled the criteria for liver transplantation (LTx). In patients with acute liver failure (ALF), as compared to those with acute decompensation of chronic liver failure (AcOChr), levels of leucine and isoleucine were significantly higher before MARS(R) treatment. In all patients, before MARS(R) treatment the higher the grade of HE grade the lower was the Fischer's ratio and higher were the levels of inhibitory neuroactive amino acids. During MARS(R) treatments the Fischer's ratio increased, and the grade of HE decreased. The increase in Fischer's ratio was mainly due to the decrease in AAAs. The plasma levels of neuroactive amino acids, methionine, glutamine, glutamate, histidine and taurine decreased during MARS(R)-treatment. In this study MARS(R)-albumin dialysis had a favorable effect on the plasma amino acid profile of patients with HE.

Tryptophan, kynurenine, and kynurenine metabolites: Relationship to lifetime aggression and inflammatory markers in human subjects

PubMed Central

Coccaro, Emil F.; Lee, Royce; Fanning, Jennifer R.; Fuchs, Dietmar; Goiny, Michel; Erhardt, Sophie; Christensen, Kyle; Brundin, Lena; Coussons-Read, Mary

2017-01-01

Inflammatory proteins are thought to be causally involved in the generation of aggression, possibly due to direct effects of cytokines in the central nervous system and/or by generation of inflammatory metabolites along the tryptophan-kynurenine (TRP/KYN) pathway, including KYN and its active metabolites kynurenic acid (KA), quinolinic acid (QA), and picolinic acid (PA). We examined plasma levels of TRP, KYN, KA, QA, and PA in 172 medication-free, medically healthy, human subjects to determine if plasma levels of these substances are altered as a function of trait aggression, and if they correlate with current plasma levels of inflammatory markers. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble interleukin-1 receptor-II (sIL-1RII) protein were also available in these subjects. We found normal levels of TRP but reduced plasma levels of KYN (by 48%), QA (by 6%), and a QA/KA (by 5%) ratio in subjects with Intermittent Explosive Disorder (IED) compared to healthy controls and psychiatric controls. Moreover, the metabolites were not associated with any of the inflammatory markers studied. These data do not support the hypothesis that elevated levels of KYN metabolites would be present in plasma of subjects with IED, and associated with plasma inflammation. However, our data do point to a dysregulation of the KYN pathway metabolites in these subjects. Further work will be necessary to replicate these findings and to understand their role in inflammation and aggression in these subjects. PMID:27318828

Plasma metabolic profiling of dairy cows affected with clinical ketosis using LC/MS technology.

PubMed

Li, Y; Xu, C; Xia, C; Zhang, Hy; Sun, Lw; Gao, Y

2014-01-01

Ketosis in dairy cattle is an important metabolic disorder. Currently, the plasma metabolic profile of ketosis as determined using liquid chromatography-mass spectrometry (LC/MS) has not been reported. To investigate plasma metabolic profiles from cows with clinical ketosis in comparison to control cows. Twenty Holstein dairy cows were divided into two groups based on clinical signs and plasma β-hydroxybutyric acid and glucose concentrations 7-21 days postpartum: clinical ketosis and control cows. Plasma metabolic profiles were analyzed using LC/MS. Data were processed using principal component analysis and orthogonal partial least-squares discriminant analysis. Compared to control cows, the levels of valine, glycine, glycocholic, tetradecenoic acid, and palmitoleic acid increased significantly in clinical ketosis. On the other hand, the levels of arginine, aminobutyric acid, leucine/isoleucine, tryptophan, creatinine, lysine, norcotinine, and undecanoic acid decreased markedly. Our results showed that the metabolic changes in cows with clinical ketosis involve complex metabolic networks and signal transduction. These results are important for future studies elucidating the pathogenesis, diagnosis, and prevention of clinical ketosis in dairy cows.

Interaction of Atmospheric-Pressure Air Microplasmas with Amino Acids as Fundamental Processes in Aqueous Solution

PubMed Central

Zhou, Renwu; Zhou, Rusen; Zhuang, Jinxing; Zong, Zichao; Zhang, Xianhui; Liu, Dongping; Bazaka, Kateryna; Ostrikov, Kostya

2016-01-01

Plasma medicine is a relatively new field that investigates potential applications of cold atmospheric-pressure plasmas in bioengineering, such as for bacterial inactivation and degradation of organic molecules in water. In order to enunciate mechanisms of bacterial inactivation at molecular or atomic levels, we investigated the interaction of atmospheric-pressure air microplasmas with amino acids in aqueous solution by using high-resolution mass spectrometry (HRMS). Results show that the oxidation effect of plasma-induced species on the side chains of the amino acids can be categorized into four types, namely hydroxylation, nitration, dehydrogenation and dimerization. In addition, relative activities of amino acids resulting from plasma treatment come in descending order as follows: sulfur-containing carbon-chain amino acids > aromatic amino acids > five-membered ring amino acids > basic carbon-chain amino acids. Since amino acids are building blocks of proteins vital to the growth and reproduction of bacteria, these results provide an insight into the mechanism of bacterial inactivation by plasma. PMID:27183129

Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats.

PubMed

Latha, M; Pari, L

2005-02-01

The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect.

Effects of Alpha-Lipoic Acid Supplementation on Plasma Adiponectin Levels and Some Metabolic Risk Factors in Patients with Schizophrenia.

PubMed

Vidović, Bojana; Milovanović, Srđan; Stefanović, Aleksandra; Kotur-Stevuljević, Jelena; Takić, Marija; Debeljak-Martačić, Jasmina; Pantović, Maja; Đorđević, Brižita

2017-01-01

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

Alteration in plasma free amino acid levels and its association with gout.

PubMed

Mahbub, M H; Yamaguchi, Natsu; Takahashi, Hidekazu; Hase, Ryosuke; Amano, Hiroki; Kobayashi-Miura, Mikiko; Kanda, Hideyuki; Fujita, Yasuyuki; Yamamoto, Hiroshi; Yamamoto, Mai; Kikuchi, Shinya; Ikeda, Atsuko; Kageyama, Naoko; Nakamura, Mina; Ishimaru, Yasutaka; Sunagawa, Hiroshi; Tanabe, Tsuyoshi

2017-03-16

Studies on the association of plasma-free amino acids with gout are very limited and produced conflicting results. Therefore, we sought to explore and characterize the plasma-free amino acid (PFAA) profile in patients with gout and evaluate its association with the latter. Data from a total of 819 subjects (including 34 patients with gout) undergoing an annual health examination program in Shimane, Japan were considered for this study. Venous blood samples were collected from the subjects and concentrations of 19 plasma amino acids were determined by high-performance liquid chromatography-electrospray ionization-mass spectrometry. Student's t-test was applied for comparison of variables between patient and control groups. The relationships between the presence or absence of gout and individual amino acids were investigated by logistic regression analysis controlling for the effects of potential demographic confounders. Among 19 amino acids, the levels of 10 amino acids (alanine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, serine, tryptophan, valine) differed significantly (P < .001 to .05) between the patient and control groups. Univariate logistic regression analysis revealed that plasma levels of alanine, isoleucine, leucine, phenylalanine, tryptophan and valine had significant positive associations (P < .005 to .05) whereas glycine and serine had significant inverse association (P < .05) with gout. The observed significant changes in PFAA profiles may have important implications for improving our understanding of pathophysiology, diagnosis and prevention of gout. The findings of this study need further confirmation in future large-scale studies involving a larger number of patients with gout.

Protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine induced acute liver injury in rats.

PubMed

Akashi, Iwao; Kagami, Keisuke; Hirano, Toshihiko; Oka, Kitaro

2009-04-01

The protective effects of coffee-derived compounds on lipopolysaccharide/D-galactosamine (LPS/D-GalN) induced acute liver injury in rats were investigated. Wistar rats were orally administered saline (control) or one of the test compounds (caffeine, chlorogenic acid, trigonelline, nicotinic acid or eight pyrazinoic acids) at a dose of 100 mg/kg, respectively. This was followed by intraperitoneal injection with LPS (100 mug/kg)/D-GalN (250 mg/kg) 1 h after administration of the test compounds. Blood samples were collected up to 12 h after LPS/D-GalN injection, followed by determination of plasma aspartate aminotransferase, alanine aminotransferase, tumour necrosis factor alpha (TNF-alpha) and interleukin 10 (IL-10) levels. Plasma aspartate aminotransferase and alanine aminotransferase levels were significantly increased after LPS/D-GalN-treatment, but were suppressed by pretreatment with caffeine (n = 5), nicotinic acid, non-substituted pyrazinoic acid or 5-methylpyrazinoic acid (n = 6, respectively) 12 h after LPS/D-GalN-treatment (P < 0.01, respectively). Moreover, the animals pretreated with these test compounds showed significantly higher survival rates (83-100%) compared with the control (23%). Only pretreatment with caffeine significantly suppressed the LPS/D-GalN induced elevation of plasma TNF-alpha levels 1 and 2 h after LPS/D-GalN-treatment (P < 0.01, respectively). Pretreatment with caffeine, nicotinic acid or non-substituted pyrazinoic acid activated the LPS/D-GalN induced elevation of plasma IL-10 levels at 1 and 2 h, although there were no statistically significant differences in IL-10 levels between control and nicotinic acid or non-substituted pyrazinoic acid treated rats. The results suggest that caffeine, nicotinic acid, non-substituted pyrazinoic acid and 5-methylpyrazinoic acid can protect against LPS/D-GalN induced acute liver injury, which may be mediated by the reduction of TNF-alpha production and/or increasing IL-10 production.

Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

PubMed

van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

2016-07-01

Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined.

Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters.

PubMed

Wilson, Thomas A; Nicolosi, Robert J; Woolfrey, Benjamin; Kritchevsky, David

2007-02-01

Our laboratory has reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Because RBO has a greater content of the unsaponifiables, which also lower cholesterol compared to most vegetable oils, we wanted to know whether oryzanol or ferulic acid, two major unsaponifiables in RBO, has a greater cholesterol-lowering activity. Forty-eight F(1)B Golden Syrian hamsters (Mesocricetus auratus) (BioBreeders, Watertown, MA) were group housed (three per cage) in cages with bedding in an air-conditioned facility maintained on a 12-h light/dark cycle. The hamsters were fed a chow-based hypercholesterolemic diet (HCD) containing 10% coconut oil and 0.1% cholesterol for 2 weeks, at which time they were bled after an overnight fast (16 h) and segregated into 4 groups of 12 with similar plasma cholesterol concentrations. Group 1 (control) continued on the HCD, group 2 was fed the HCD containing 10% RBO in place of coconut oil, group 3 was fed the HCD plus 0.5% ferulic acid and group 4 was fed the HCD plus 0.5% oryzanol for an additional 10 weeks. After 10 weeks on the diets, plasma total cholesterol (TC) and non-high-density lipoprotein cholesterol (HDL-C) (very low- and low-density lipoprotein) concentrations were significantly lower in the RBO (-64% and -70%, respectively), the ferulic acid (-22% and -24%, respectively) and the oryzanol (-70% and -77%, respectively) diets compared to control. Plasma TC and non-HDL-C concentrations were also significantly lower in the RBO (-53% and -61%, respectively) and oryzanol (-61% and -70%, respectively) diets compared to the ferulic acid. Compared to control and ferulic acid, plasma HDL-C concentrations were significantly higher in the RBO (10% and 20%, respectively) and oryzanol (13% and 24%, respectively) diets. The ferulic acid diet had significantly lower plasma HDL-C concentrations compared to the control (-9%). The RBO and oryzanol diets were significantly lower for plasma triglyceride concentrations compared to the control (-53% and -65%, respectively) and ferulic acid (-47% and -60%, respectively) diets. Hamsters fed the control and ferulic acid diets had significantly higher plasma vitamin E concentrations compared to the RBO (201% and 161%, respectively) and oryzanol (548% and 462%, respectively) diets; the ferulic acid and oryzanol diets had significantly lower plasma lipid hydroperoxide levels than the control (-57% and -46%, respectively) diet. The oryzanol-fed hamsters excreted significantly more coprostenol and cholesterol in their feces than the ferulic acid (127% and 120%, respectively) diet. The control diet had significantly greater aortic TC and FC accumulation compared to the RBO (115% and 89%, respectively), ferulic acid (48% and 58%, respectively) and the oryzanol (74% and 70%, respectively) diets. However, only the RBO and oryzanol diets had significantly lower aortic cholesterol ester accumulation compared to the control (-73% and -46%, respectively) diet. The present study suggests that at equal dietary levels, oryzanol has a greater effect on lowering plasma non-HDL-C levels and raising plasma HDL-C than ferulic acid, possibly through a greater extent to increase fecal excretion of cholesterol and its metabolites. However, ferulic acid may have a greater antioxidant capacity via its ability to maintain serum vitamin E levels compared to RBO and oryzanol. Thus, both oryzanol and ferulic acid may exert similar antiatherogenic properties, but through different mechanisms.

A fish protein hydrolysate alters fatty acid composition in liver and adipose tissue and increases plasma carnitine levels in a mouse model of chronic inflammation.

PubMed

Bjørndal, Bodil; Berge, Christ; Ramsvik, Marie Sannes; Svardal, Asbjørn; Bohov, Pavol; Skorve, Jon; Berge, Rolf K

2013-10-07

There is growing evidence that fish protein hydrolysate (FPH) diets affect mitochondrial fatty acid metabolism in animals. The aim of the study was to determine if FPH could influence fatty acid metabolism and inflammation in transgene mice expressing human tumor necrosis factor alpha (hTNFα). hTNFα mice (C57BL/6 hTNFα) were given a high-fat (23%, w/w) diet containing 20% casein (control group) or 15% FPH and 5% casein (FPH group) for two weeks. After an overnight fast, blood, adipose tissue, and liver samples were collected. Gene expression and enzyme activity was analysed in liver, fatty acid composition was analyzed in liver and ovarian white adipose tissue, and inflammatory parameters, carnitine, and acylcarnitines were analyzed in plasma. The n-3/n-6 fatty acid ratio was higher in mice fed the FPH diet than in mice fed the control diet in both adipose tissue and liver, and the FPH diet affected the gene expression of ∆6 and ∆9 desaturases. Mice fed this diet also demonstrated lower hepatic activity of fatty acid synthase. Concomitantly, a lower plasma INF-γ level was observed. Plasma carnitine and the carnitine precursor γ-butyrobetaine was higher in the FPH-group compared to control, as was plasma short-chained and medium-chained acylcarnitine esters. The higher level of plasma acetylcarnitine may reflect a stimulated mitochondrial and peroxisomal β-oxidation of fatty acids, as the hepatic activities of peroxisomal acyl-CoA oxidase 1 and mitochondrial carnitine palmitoyltransferase-II were higher in the FPH-fed mice. The FPH diet was shown to influence hepatic fatty acid metabolism and fatty acid composition. This indicates that effects on fatty acid metabolism are important for the bioactivity of protein hydrolysates of marine origin.

Hyperuricemia Is a Risk Factor for the Onset of Impaired Fasting Glucose in Men with a High Plasma Glucose Level: A Community-Based Study

PubMed Central

Miyake, Teruki; Kumagi, Teru; Furukawa, Shinya; Hirooka, Masashi; Kawasaki, Keitarou; Koizumi, Mitsuhito; Todo, Yasuhiko; Yamamoto, Shin; Abe, Masanori; Kitai, Kohichiro; Matsuura, Bunzo; Hiasa, Yoichi

2014-01-01

Background It is not clear whether elevated uric acid is a risk factor for the onset of impaired fasting glucose after stratifying by baseline fasting plasma glucose levels. We conducted a community-based retrospective longitudinal cohort study to clarify the relationship between uric acid levels and the onset of impaired fasting glucose, according to baseline fasting plasma glucose levels. Methods We enrolled 6,403 persons (3,194 men and 3,209 women), each of whom was 18–80 years old and had >2 annual check-ups during 2003–2010. After excluding persons who had fasting plasma glucose levels ≥6.11 mM and/or were currently taking anti-diabetic agents, the remaining 5,924 subjects were classified into quartiles according to baseline fasting plasma glucose levels. The onset of impaired fasting glucose was defined as fasting plasma glucose ≥6.11 mM during the observation period. Results In the quartile groups, 0.9%, 2.1%, 3.4%, and 20.2% of the men developed impaired fasting glucose, respectively, and 0.1%, 0.3%, 0.5%, and 5.6% of the women developed impaired fasting glucose, respectively (P trend <0.001). After adjusting for age, body mass index, systolic blood pressure, triacylglycerols, high density lipoprotein-cholesterol, creatinine, fatty liver, family history of diabetes, alcohol consumption, and current smoking, uric acid levels were positively associated with onset of impaired fasting glucose in men with highest-quartile fasting plasma glucose levels (adjusted hazard ratio, 1.003; 95% confidence interval, 1.0001–1.005, P = 0.041). Conclusions Among men with high fasting plasma glucose, hyperuricemia may be independently associated with an elevated risk of developing impaired fasting glucose. PMID:25237894

Urinary Phenylacetylglutamine as Dosing Biomarker for Patients with Urea Cycle Disorders

PubMed Central

Mokhtarani, M; Diaz, GA; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, SA; Gallagher, R; Bartholomew, D; Harding, CO; Korson, MS; McCandless, SE; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, JL; Sreenath-Nagamani, Sandesh; Summar, M; LeMons, C; Dickinson, K; Coakley, DF; Moors, TL; Lee, B; Scharschmidt, BF

2013-01-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). Study Design These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6–17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Results Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5–31.8 g/day and of sodium phenylbutyrate ranging from 1.3–31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% –5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% -to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r=0.730, p<0.001) or as total 24-hour excretion (r=0.791 p<0.001), followed by plasma phenylacetylglutamine AUC24-hour, plasma phenylacetic acid AUC24-hour and phenylbutyric acid AUC24-hour. Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. Conclusion The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. PMID:22958974

Urinary phenylacetylglutamine as dosing biomarker for patients with urea cycle disorders.

PubMed

Mokhtarani, M; Diaz, G A; Rhead, W; Lichter-Konecki, U; Bartley, J; Feigenbaum, A; Longo, N; Berquist, W; Berry, S A; Gallagher, R; Bartholomew, D; Harding, C O; Korson, M S; McCandless, S E; Smith, W; Vockley, J; Bart, S; Kronn, D; Zori, R; Cederbaum, S; Dorrani, N; Merritt, J L; Sreenath-Nagamani, Sandesh; Summar, M; Lemons, C; Dickinson, K; Coakley, D F; Moors, T L; Lee, B; Scharschmidt, B F

2012-11-01

We have analyzed pharmacokinetic data for glycerol phenylbutyrate (also GT4P or HPN-100) and sodium phenylbutyrate with respect to possible dosing biomarkers in patients with urea cycle disorders (UCD). These analyses are based on over 3000 urine and plasma data points from 54 adult and 11 pediatric UCD patients (ages 6-17) who participated in three clinical studies comparing ammonia control and pharmacokinetics during steady state treatment with glycerol phenylbutyrate or sodium phenylbutyrate. All patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate or sodium phenylbutyrate in a cross over fashion and underwent 24-hour blood samples and urine sampling for phenylbutyric acid, phenylacetic acid and phenylacetylglutamine. Patients received phenylbutyric acid equivalent doses of glycerol phenylbutyrate ranging from 1.5 to 31.8 g/day and of sodium phenylbutyrate ranging from 1.3 to 31.7 g/day. Plasma metabolite levels varied widely, with average fluctuation indices ranging from 1979% to 5690% for phenylbutyric acid, 843% to 3931% for phenylacetic acid, and 881% to 1434% for phenylacetylglutamine. Mean percent recovery of phenylbutyric acid as urinary phenylacetylglutamine was 66.4 and 69.0 for pediatric patients and 68.7 and 71.4 for adult patients on glycerol phenylbutyrate and sodium phenylbutyrate, respectively. The correlation with dose was strongest for urinary phenylacetylglutamine excretion, either as morning spot urine (r = 0.730, p < 0.001) or as total 24-hour excretion (r = 0.791 p<0.001), followed by plasma phenylacetylglutamine AUC(24-hour), plasma phenylacetic acid AUC(24-hour) and phenylbutyric acid AUC(24-hour). Plasma phenylacetic acid levels in adult and pediatric patients did not show a consistent relationship with either urinary phenylacetylglutamine or ammonia control. The findings are collectively consistent with substantial yet variable pre-systemic (1st pass) conversion of phenylbutyric acid to phenylacetic acid and/or phenylacetylglutamine. The variability of blood metabolite levels during the day, their weaker correlation with dose, the need for multiple blood samples to capture trough and peak, and the inconsistency between phenylacetic acid and urinary phenylacetylglutamine as a marker of waste nitrogen scavenging limit the utility of plasma levels for therapeutic monitoring. By contrast, 24-hour urinary phenylacetylglutamine and morning spot urine phenylacetylglutamine correlate strongly with dose and appear to be clinically useful non-invasive biomarkers for compliance and therapeutic monitoring. Copyright © 2012 Elsevier Inc. All rights reserved.

Modulation of C-reactive protein and plasma omega-6 fatty acid levels by phospholipase A2 gene polymorphisms following a 6-week supplementation with fish oil.

PubMed

Tremblay, B L; Rudkowska, I; Couture, P; Lemieux, S; Julien, P; Vohl, M C

2015-12-01

This clinical trial investigated the impact of a six-week supplementation with fish oil and single nucleotide polymorphisms (SNPs) in PLA2G4A and PLA2G6 genes on total omega-6 fatty acid (n-6 FA) levels in plasma phospholipids (PL) and plasma C-reactive protein (CRP) levels in 191 subjects. Interaction effects between SNPs and supplementation modulated total n-6 FAs and CRP levels in both men and women. Associations between SNPs and total n-6 FA levels and between SNPs and CRP levels were identified in men, independently of supplementation. Supplementation decreased total n-6 FAs without affecting plasma CRP levels. Changes in CRP levels correlated positively with changes in total n-6 FAs in men (r=0.25 p=0.01), but not in women. In conclusion, total n-6 FA levels in plasma PL and plasma CRP levels are modulated by SNPs within PLA2G4A and PLA2G6 genes alone or in combination with fish oil supplementation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Arginine supplementation modulates pig plasma lipids, but not hepatic fatty acids, depending on dietary protein level with or without leucine.

PubMed

Madeira, Marta Sofia Morgado Dos Santos; Rolo, Eva Sofia Alves; Pires, Virgínia Maria Rico; Alfaia, Cristina Maria Riscado Pereira Mateus; Coelho, Diogo Francisco Maurício; Lopes, Paula Alexandra Antunes Brás; Martins, Susana Isabel Vargas; Pinto, Rui Manuel Amaro; Prates, José António Mestre

2017-05-30

In the present study, the effect of arginine and leucine supplementation, and dietary protein level, were investigated in commercial crossbred pigs to clarify their individual or combined impact on plasma metabolites, hepatic fatty acid composition and mRNA levels of lipid sensitive factors. The experiment was conducted on fifty-four entire male pigs (Duroc × Pietrain × Large White × Landrace crossbred) from 59 to 92 kg of live weight. Each pig was randomly assigned to one of six experimental treatments (n = 9). The treatments followed a 2 × 3 factorial arrangement, providing two levels of arginine supplementation (0 vs. 1%) and three levels of basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet with 2% of leucine, RPDL). Significant interactions between arginine supplementation and protein level were observed across plasma lipids. While dietary arginine increased total lipids, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol and triacylglycerols in NPD, the inverse effect was observed in RPD. Overall, dietary treatments had a minor impact on hepatic fatty acid composition. RPD increased 18:1c9 fatty acid while the combination of leucine and RPD reduced 18:0 fatty acid. Arginine supplementation increased the gene expression of FABP1, which contributes for triacylglycerols synthesis without affecting hepatic fatty acids content. RPD, with or without leucine addition, upregulated the lipogenic gene CEBPA but downregulated the fat oxidation gene LPIN1. Arginine supplementation was responsible for a modulated effect on plasma lipids, which is dependent on dietary protein level. It consistently increased lipaemia in NPD, while reducing the correspondent metabolites in RPD. In contrast, arginine had no major impact, neither on hepatic fatty acids content nor on fatty acid composition. Likewise, leucine supplementation of RPD, regardless the presence of arginine, promoted no changes on total fatty acids in the liver. Ultimately, arginine, leucine and dietary protein reduction seem to be unrelated with fatty liver development.

Effect of mental stress on plasma homovanillic acid in healthy human subjects.

PubMed

Sumiyoshi, T; Yotsutsuji, T; Kurachi, M; Itoh, H; Kurokawa, K; Saitoh, O

1998-07-01

Plasma levels of homovanillic acid (pHVA) have been suggested to provide a measure of dopaminergic activity in the central nervous system. The present study investigated the effect of mental stress by the Kraepelin test, a test of continuous arithmetic addition of single-digit figures for 30 min, on pHVA levels in 13 male psychiatrically normal healthy volunteers. Following an overnight fast and restricted physical activity, plasma samples were collected immediately before and after the administration of the Kraepelin test. Plasma HVA levels following the administration of the Kraepelin test were significantly lower than the pretest pHVA levels. The percent change in pHVA levels by the Kraepelin test positively correlated with pretest pHVA levels. The observed reduction in pHVA levels by mental stress in normal subjects may reflect some aspects of a dopamine-dependent restitutive system in the brain.

Composition of fatty acids in plasma and erythrocytes and eicosanoids level in patients with metabolic syndrome

PubMed Central

2011-01-01

Background Disturbances of the fatty acids composition in plasma and red blood cells and eicosanoid synthesis play an important role in the metabolic syndrome (MS) formation. Methods The observation group included 61 people with metabolic syndrome (30 patients with MS and normal levels of insulin, 31 people with MS and insulin resistance - IR). The parameters of carbohydrate and lipid metabolism in blood serum were examined. The composition of nonesterified fatty acids (NEFA), fatty acid (FA) of red blood cells lipids was analyzed by gas-liquid chromatography. Eicosanoids level in MS patients blood serum was studied by enzyme immunoassay. Results In MS patients in the absence of glucose-insulin homeostasis disturbances and in patients with IR the accumulation of polyunsaturated fatty acids (18:2 n6, 18:3 n3, 22:4 n6) and lower pool of saturated FA (12:0, 14:0, 16: 0, 17:0) in plasma were discovered. A deficit of polyunsaturated FA (18:3 n3, 20:4 n6) with a predominance of on-saturated FA (14:0, 18:0) in erythrocyte membranes was revealed. In MS patients regardless of the carbohydrate metabolism status high levels of leukotriene B4 and 6-keto-prostaglandin-F1α in serum were found. The development of IR in MS patients leads to increased synthesis of thromboxane A2. Conclusion The results revealed a disturbance in nonesterified fatty acids of plasma lipids and red blood cells, eicosanoid synthesis in MS patients. The breach of the plasma and cell membranes fatty acids compositions, synthesis of vasoactive and proinflammatory eicosanoids is an important pathogenetic part of the MS development. PMID:21595891

Plasma Levels of Eicosapentaenoic Acid Are Associated with Anti-TNF Responsiveness in Rheumatoid Arthritis and Inhibit the Etanercept-driven Rise in Th17 Cell Differentiation in Vitro.

PubMed

Jeffery, Louisa; Fisk, Helena L; Calder, Philip C; Filer, Andrew; Raza, Karim; Buckley, Christopher D; McInnes, Iain; Taylor, Peter C; Fisher, Benjamin A

2017-06-01

To determine whether levels of plasma n-3 polyunsaturated fatty acids are associated with response to antitumor necrosis factor (anti-TNF) agents in rheumatoid arthritis (RA), and whether this putative effect may have its basis in altering anti-TNF-driven Th17 cell differentiation. Plasma was collected at baseline and after 3 months of anti-TNF treatment in 22 patients with established RA, and fatty acid composition of the phosphatidylcholine (PC) component was measured. CD4+CD25- T cells and monocytes were purified from the blood of healthy donors and cocultured in the presence of anti-CD3, with or without etanercept (ETN), eicosapentaenoic acid (EPA), or the control fatty acid, linoleic acid (LA). Expression of interleukin 17 and interferon-γ was measured by intracellular staining and flow cytometry. Plasma PC EPA levels and the EPA/arachidonic acid ratio correlated inversely with change in the Disease Activity Score at 28 joints (DAS28) at 3 months (-0.51, p = 0.007 and -0.48, p = 0.01, respectively), indicating that higher plasma EPA was associated with a greater reduction in DAS28. Plasma PC EPA was positively associated with European League Against Rheumatism response (p = 0.02). An increase in Th17 cells post-therapy has been associated with nonresponse to anti-TNF. ETN increased Th17 frequencies in vitro . Physiological concentrations of EPA, but not LA, prevented this. EPA status was associated with clinical improvements to anti-TNF therapy in vivo and prevented the effect of ETN on Th17 cells in vitro . EPA supplementation might be a simple way to improve anti-TNF outcomes in patients with RA by suppressing Th17 frequencies.

Flying-fox (Pteropus spp.) sperm membrane fatty acid composition, its relationship to cold shock injury and implications for cryopreservation success.

PubMed

Melville, D F; Johnston, S D; Miller, R R

2012-12-01

The very large acrosome of Pteropus species spermatozoa is prone to damage during cooling procedures. Cryogenic succuss has been linked to membrane composition, therefore the lipid composition of five Pteropus species sperm acrosomal and plasma membranes were investigated to provide insight into reasons for cold shock susceptibility. Rapid chilling and re-warming of spermatozoa from three Pteropus species resulted in a decrease (P<0.05) in acrosomal integrity. Biochemical analysis of lipids revealed that stearic acid (18:0) was the predominant saturated fatty acid and oleic acid (18:1, n-9) the predominant unsaturated fatty acid in both acrosomal and plasma membranes. Linolenic acid (18:3, n-3) was only detected in plasma membranes of Pteropus hypomelanus and was detected in acrosomal membranes of all Pteropus spp. studied (except Pteropus giganteus). Although detected in both plasma and acrosomal membranes of Pteropus vampyrus, docosahexaenoic acid (22:6) was not detected at all in Pteropus poliocephalus, only in trace levels in the acrosomal and plasma membranes of P. giganteus and P. hypomelanus and not in acrosomal membranes of Pteropus rodricensis. No difference was seen in the levels of polyunsaturated fatty acids (PUFAs) within plasma membranes, however PUFAs were lower (P<0.05) in acrosomal membranes of P. giganteus compared with P. vampyrus. Pteropus spp. spermatozoa have a very low ratio of unsaturated/saturated membrane fatty acids (<0.5). Membranes containing more PUFAs are more fluid, so the use of cryogenic media which improves membrane fluidity should improve Pteropus spp. spermatozoal viability post-thaw. Copyright © 2012 Elsevier Inc. All rights reserved.

[Resorption of hydrocyanic acid from linseed].

PubMed

Schulz, V; Löffler, A; Gheorghiu, T

1983-01-01

Resorption of hydrocyanic acid after ingestion of linseed was investigated in 20 healthy volunteers and 5 patients. The persons investigated took a single dose of 30 g or of 100 g of linseed or they received throughout several weeks 15 g. t.i.d. One volunteer also took for purposes of comparison bitter almonds or potassium cyanide. Before, during and after the periods of ingestion plasma levels of hydrocyanic acid and of thiocyanate were normal. During long-term trials urinary excretion of thiocyanate was monitored regularly. Intake of linseed even in extremely high dosages never caused significant rises of plasma thiocyanate levels; this, however, was the case after intake of bitter almonds or potassium cyanide. Thus, it can be excluded, that intoxication by hydrocyanic acid can be caused by linseed. Long-term intake of linseed however, raised plasma levels of thiocyanate significantly; at the same time urinary excretion of thiocyanate increased.

Uric acid but not apple polyphenols is responsible for the rise of plasma antioxidant activity after apple juice consumption in healthy subjects.

PubMed

Godycki-Cwirko, Maciek; Krol, Maciej; Krol, Bogusław; Zwolinska, Anna; Kolodziejczyk, Krzysztof; Kasielski, Marek; Padula, Gianluca; Grebowski, Jacek; Grębocki, Jacek; Kazmierska, Paulina; Kazimierska, Paulina; Miatkowski, Marcin; Markowski, Jarosław; Nowak, Dariusz

2010-08-01

To determine whether (1) rapid consumption of 1 L of apple juice increases blood antioxidant capacity, measured as ferric-reducing ability of plasma (FRAP) and serum 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity, and (2) apple polyphenols or fructose-induced elevation of plasma uric acid contributes to post-juice increase of blood antioxidant activity. The study involved 12 (mean age 32 ± 5 years, mean body weight 73 ± 7 kg) healthy nonsmoking subjects. Tested subjects consumed 1 L of clear apple juice and then FRAP; serum DPPH-scavenging activity, serum uric acid, and total plasma phenolics and quercetin levels were measured just before juice ingestion and 1, 2.5, and 4 hours after ingestion. This was repeated 3 times with 4-day intervals, but volunteers drank either 1 L of clear apple juice without polyphenols (placebo), or 1 L of cloudy apple juice (positive control), or 1 L of water (negative control) at the time. All juices had similar content of sugars (i.e., saccharose, glucose, and fructose) and precisely defined composition of phenolics and antioxidant activity. Consumption of all 3 juices transiently increased FRAP and serum DPPH-scavenging activity, with peak values at 1 hour post-juice ingestion. This was paralleled by the rise of serum uric acid, but no significant changes in plasma total phenolics and quercetin levels were observed after all dietary interventions. At the same time, no substantial differences were found between juices (especially between clear apple juice and clear apple juice without polyphenols) concerning the measured variables. A strong significant correlation was noted instead between serum uric acid and plasma antioxidant activity at all analyzed time points, before and after juice ingestion. Plasma total phenolics and quercetin levels were not associated with FRAP and serum DPPH radical-scavenging activity. We have demonstrated that rapid consumption of apple juice increased plasma antioxidant activity in healthy subjects; this was caused by the fructose-induced rise of serum uric acid levels, but was not due to the presence of antioxidant polyphenols in juice. Thus, short-term consumption of apple juice seems not to be the effective dietary intervention to augment plasma antioxidant activity due to the concomitant possibility for uric acid to be a risk factor for several diseases, as verified by other authors.

Caffeic acid as active principle from the fruit of Xanthium strumarium to lower plasma glucose in diabetic rats.

PubMed

Hsu, F L; Chen, Y C; Cheng, J T

2000-04-01

The antihyperglycemic effect of caffeic acid, one of the phenolic compounds contained in the fruit of Xanthium strumarium, was investigated. After an intravenous injection of caffeic acid into diabetic rats of both streptozotocin-induced and insulin-resistant models, a dose-dependent decrease of plasma glucose was observed. However, a similar effect was not produced in normal rats. An insulin-independent action of caffeic acid can thus be considered. Otherwise, this compound reduced the elevation of plasma glucose level in insulin-resistant rats receiving a glucose challenge test. Also, glucose uptake into the isolated adipocytes was raised by caffeic acid in a concentration-dependent manner. Increase of glucose utilization by caffeic acid seems to be responsible for the lowering of plasma glucose.

Small, qualitative changes in fatty acid intake decrease plasma low-density lipoprotein-cholesterol levels in mildly hypercholesterolemic outpatients on their usual high-fat diets.

PubMed

Lecerf, Jean-Michel; Luc, Gérald; Marécaux, Nadine; Bal, Sylvie; Bonte, Jean-Paul; Lacroix, Brigitte; Cayzeele, Amélie

2009-01-01

The diet is the first step in managing hypercholesterolemia. The objective of the present study is to assess whether moderate changes in dietary fatty acids improve plasma lipid parameters in mildly hypercholesterolemic outpatients. Using a randomized double-blind study, 121 outpatients within two groups received an isocaloric amount of unsaturated margarine or butter. Clinical and anthropometric measurements and a 3-day food record were made. Chi-square and Fisher's tests were used to compare qualitative variables and the general linear procedure was used to compare the groups. Additional analyses were performed after adjustment. There was a significant difference (P <0.03) in low-density lipoprotein-cholesterol levels between the groups. Total cholesterol, low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol and apolipoprotein B values decreased in the unsaturated group in comparison with the saturated group. Low-density lipoprotein-cholesterol changes were correlated with the variation in polyunsaturated fatty acid intake and with plasma phospholipid linoleic acid levels. A small change in saturated by polyunsaturated fatty acid intake may improve plasma lipid parameters in mildly hypercholesterolemic subjects.

Lower Concentrations of Circulating Medium and Long-Chain Acylcarnitines Characterize Insulin Resistance in Persons with HIV.

PubMed

Bailin, Samuel S; Jenkins, Cathy A; Petucci, Christopher; Culver, Jeffrey A; Shepherd, Bryan E; Fessel, Joshua P; Hulgan, Todd; Koethe, John R

2018-05-02

In human immunodeficiency virus (HIV)-negative individuals, a plasma metabolite profile, characterized by higher levels of branched-chain amino acids (BCAA), aromatic amino acids, and C3/C5 acylcarnitines, is associated with insulin resistance and increased risk of diabetes. We sought to characterize the metabolite profile accompanying insulin resistance in HIV-positive persons to assess whether the same or different bioenergetics pathways might be implicated. We performed an observational cohort study of 70 nondiabetic, HIV-positive individuals (50% with body mass index ≥30 kg/m 2 ) on efavirenz, tenofovir, and emtricitabine with suppressed HIV-1 RNA levels (<50 copies/mL) for at least 2 years and a CD4 + count over 350 cells/μL. We measured fasting insulin resistance using the homeostatic model assessment 2, plasma free fatty acids (FFA) using gas chromatography, and amino acids, acylcarnitines, and organic acids using liquid chromatography/mass spectrometry. We assessed the relationship of plasma metabolites with insulin resistance using multivariable linear regression. The median age was 45 years, median CD4 + count was 701 cells/μL, and median hemoglobin A1c was 5.2%. Insulin resistance was associated with higher plasma C3 acylcarnitines (p = .01), but not BCAA or C5 acylcarnitines. However, insulin resistance was associated with lower plasma levels of C18, C16, C12, and C2 acylcarnitines (p ≤ .03 for all), and lower C18 and C16 acylcarnitine:FFA ratios (p = .002, and p = .03, respectively). In HIV-positive persons, lower levels of plasma acylcarnitines, including the C2 product of complete fatty acid oxidation, are a more prominent feature of insulin resistance than changes in BCAA, suggesting impaired fatty acid uptake and/or mitochondrial oxidation is a central aspect of glucose intolerance in this population.

Mechanism of insulin-stimulated clearance of plasma nonesterified fatty acids in humans.

PubMed

Carpentier, André C; Frisch, Frédérique; Brassard, Pascal; Lavoie, François; Bourbonnais, Annie; Cyr, Denis; Giguère, Robert; Baillargeon, Jean-Patrice

2007-03-01

Insulin increases plasma nonesterified fatty acid (NEFA) clearance in humans, but whether this is independent of change in plasma NEFA appearance is currently unknown. Nine nondiabetic men (age: 28+/-3 yr, body mass index: 27.2+/-1.7 kg/m2) underwent euglycemic clamps to maintain low (LINS) vs. high (HINS) physiological insulin levels for 6 h. An intravenous infusion of heparin+Intralipid (HI) was performed during 4 of the 6 h of the clamps (in the last 4 h at LINS and in the first 4 h at HINS), whereas saline infusion (SAL) was administered in the remaining 2 h to modulate plasma NEFA levels independently of plasma insulin levels. Four experimental conditions were obtained in each individual: LINS with saline (LINS/SAL) and with HI infusion (LINS/HI) and HINS with saline (HINS/SAL) and with HI infusion (HINS/HI). Plasma palmitate appearance during HINS/SAL was lower than during the three other experimental conditions (P<0.05). In contrast, plasma linoleate appearance, as expected, was increased by HI independently of insulin level (P<0.02). Plasma palmitate clearance during HINS/SAL was higher than LINS/SAL and LINS/HI (P<0.008), and this increase was blunted during HINS/HI. We observed a linear decrease in plasma palmitate clearance with increasing plasma NEFA appearance independent of insulin levels. Plasma NEFA levels increased exponentially with increase in plasma NEFA appearance. We conclude that insulin stimulates plasma NEFA clearance by reducing the endogenous appearance rate of NEFA. The relationship between plasma NEFA level and appearance rate is nonlinear.

Relationship Between Circulating Fatty Acids and Fatty Acid Ethanolamide Levels After a Single 2-h Dietary Fat Feeding in Male Sprague-Dawley Rats : Elevated levels of oleoylethanolamide, palmitoylethanolamide, linoleoylethanolamide, arachidonoylethanolamide and docosahexanoylethanolamide after a single 2 h dietary fat feeding in male Sprague Dawley rats.

PubMed

Olatinsu, Anthonia O; Sihag, Jyoti; Jones, Peter J H

2017-11-01

Previous studies show that long term variations in dietary fat consumption impact circulating fatty acid ethanolamide (FAE) concentrations, however, few studies have investigated short term effects of dietary fat feeding on FAE levels. The trial's objective was to explore the effect of acute feeding of varying amounts of dietary n-9 and n-3 fatty acids on plasma and organ levels of FAE. Sixty-four rats were assigned to four groups fed meals containing 40% of energy as either safflower oil (control), canola oil (CO), or DHA rich oil (DRO), each consumed as a bolus within a 2-h window. Plasma and tissue FAE levels were measured at 3, 6, 12 and 24 h following the bolus. FAE profiles over time exhibited patterns that were specific both to FAE and to dietary fat type provided. At 3 h, plasma and liver OEA levels were higher (p < 0.05) in the 95% CO:5% DRO compared with other groups. At 12 h, plasma PEA levels were lower (p < 0.05) in the 50% CO:50% DRO group compared to the 95% CO group. Plasma DEA levels showed an increase (p < 0.05) only after 24 h of feeding. All four dietary groups manifested increased DEA levels in a dose-dependent manner. Data demonstrate that a single meal feeding of diets with different ratios of fat types impacts tissue levels of FAE within a short time frame, which could further influence the physiological roles of FAE on appetite regulation and energy expenditure.

Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation.

PubMed

Liu, Yuguan; Weisberg, Lawrence S; Langman, Craig B; Logan, Amanda; Hunter, Krystal; Prasad, Deepali; Avila, Jose; Venkatchalam, Thaliga; Berns, Jeffrey S; Handelman, Garry J; Sirover, William D

2016-10-01

Ascorbic acid (AA) supplementation may increase hemoglobin levels and decrease erythropoiesis-stimulating agent dose requirement in patients with end stage renal disease (ESRD). While plasma AA levels >100μM may be supratherapeutic, levels of at least 30μM may be needed to improve wound healing and levels may need to reach 70μM to optimize erythropoiesis. Of concern, oxalate (Ox), an AA metabolite, can accumulate in ESRD. Historically, if plasma Ox levels remain ≥30μM, oxalosis was of concern. Contemporary hemodialysis (HD) efficiencies may decrease the risk of oxalosis by maintaining pre-HD Ox levels <30μM. This study focuses on the plasma Ox levels in HD patients. A prospective, observational study of 197 HD patients with pre-HD AA levels and pre-HD and post-HD Ox levels. Mean plasma Ox levels decreased 71% during the intradialytic period (22.3±11.1μM to 6.4±3.2μM, P<0.001). In regression analysis, pre-HD plasma AA levels ≤100μM were not associated with a pre-HD plasma Ox level≥30μM, even if ferritin levels were increased. Pre-HD plasma Ox levels ≥20 or ≥30μM were not associated with lower cumulative 4-year survival. Pre-HD plasma AA levels up to 100μM in HD patients do not appear to be associated with an increased risk of developing secondary oxalosis, as the corresponding pre-HD plasma Ox level appears to be maintained at tolerable levels. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Plasma Nervonic Acid Is a Potential Biomarker for Major Depressive Disorder: A Pilot Study.

PubMed

Kageyama, Yuki; Kasahara, Takaoki; Nakamura, Takemichi; Hattori, Kotaro; Deguchi, Yasuhiko; Tani, Munehide; Kuroda, Kenji; Yoshida, Sumiko; Goto, Yu-Ichi; Inoue, Koki; Kato, Tadafumi

2018-03-01

Diagnostic biomarkers of major depressive disorder, bipolar disorder, and schizophrenia are urgently needed, because none are currently available. We performed a comprehensive metabolome analysis of plasma samples from drug-free patients with major depressive disorder (n=9), bipolar disorder (n=6), schizophrenia (n=17), and matched healthy controls (n=19) (cohort 1) using liquid chromatography time-of-flight mass spectrometry. A significant effect of diagnosis was found for 2 metabolites: nervonic acid and cortisone, with nervonic acid being the most significantly altered. The reproducibility of the results and effects of psychotropic medication on nervonic acid were verified in cohort 2, an independent sample set of medicated patients [major depressive disorder (n=45), bipolar disorder (n=71), schizophrenia (n=115)], and controls (n=90) using gas chromatography time-of-flight mass spectrometry. The increased levels of nervonic acid in patients with major depressive disorder compared with controls and patients with bipolar disorder in cohort 1 were replicated in the independent sample set (cohort 2). In cohort 2, plasma nervonic acid levels were also increased in the patients with major depressive disorder compared with the patients with schizophrenia. In cohort 2, nervonic acid levels were increased in the depressive state in patients with major depressive disorder compared with the levels in the remission state in patients with major depressive disorder and the depressive state in patients with bipolar disorder. These results suggested that plasma nervonic acid is a good candidate biomarker for the depressive state of major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Interactions between dietary oil treatments and genetic variants modulate fatty acid ethanolamides in plasma and body weight composition.

PubMed

Pu, Shuaihua; Eck, Peter; Jenkins, David J A; Connelly, Philip W; Lamarche, Benoît; Kris-Etherton, Penny M; West, Sheila G; Liu, Xiaoran; Jones, Peter J H

2016-03-28

Fatty acid ethanolamides (FAE), a group of lipid mediators derived from long-chain fatty acids (FA), mediate biological activities including activation of cannabinoid receptors, stimulation of fat oxidation and regulation of satiety. However, how circulating FAE levels are influenced by FA intake in humans remains unclear. The objective of the present study was to investigate the response of six major circulating FAE to various dietary oil treatments in a five-period, cross-over, randomised, double-blind, clinical study in volunteers with abdominal obesity. The treatment oils (60 g/12 552 kJ per d (60 g/3000 kcal per d)) provided for 30 d were as follows: conventional canola oil, high oleic canola oil, high oleic canola oil enriched with DHA, flax/safflower oil blend and corn/safflower oil blend. Two SNP associated with FAE degradation and synthesis were studied. Post-treatment results showed overall that plasma FAE levels were modulated by dietary FA and were positively correlated with corresponding plasma FA levels; minor allele (A) carriers of SNP rs324420 in gene fatty acid amide hydrolase produced higher circulating oleoylethanolamide (OEA) (P=0·0209) and docosahexaenoylethanolamide (DHEA) levels (P=0·0002). In addition, elevated plasma DHEA levels in response to DHA intake tended to be associated with lower plasma OEA levels and an increased gynoid fat mass. In summary, data suggest that the metabolic and physiological responses to dietary FA may be influenced via circulating FAE. Genetic analysis of rs324420 might help identify a sub-population that appears to benefit from increased consumption of DHA and oleic acid.

Pea Fiber and Wheat Bran Fiber Show Distinct Metabolic Profiles in Rats as Investigated by a 1H NMR-Based Metabolomic Approach

PubMed Central

Liu, Guangmang; Xiao, Liang; Fang, Tingting; Cai, Yimin; Jia, Gang; Zhao, Hua; Wang, Jing; Chen, Xiaoling; Wu, Caimei

2014-01-01

This study aimed to examine the effect of pea fiber (PF) and wheat bran fiber (WF) supplementation in rat metabolism. Rats were assigned randomly to one of three dietary groups and were given a basal diet containing 15% PF, 15% WF, or no supplemental fiber. Urine and plasma samples were analyzed by NMR-based metabolomics. PF significantly increased the plasma levels of 3-hydroxybutyrate, and myo-inositol as well as the urine levels of alanine, hydroxyphenylacetate, phenylacetyglycine, and α-ketoglutarate. However, PF significantly decreased the plasma levels of isoleucine, leucine, lactate, and pyruvate as well as the urine levels of allantoin, bile acids, and trigonelline. WF significantly increased the plasma levels of acetone, isobutyrate, lactate, myo-inositol, and lipids as well as the urine levels of alanine, lactate, dimethylglycine, N-methylniconamide, and α-ketoglutarate. However, WF significantly decreased the plasma levels of amino acids, and glucose as well as the urine levels of acetate, allantoin, citrate, creatine, hippurate, hydroxyphenylacetate, and trigonelline. Results suggest that PF and WF exposure can promote antioxidant activity and can exhibit common systemic metabolic changes, including lipid metabolism, energy metabolism, glycogenolysis and glycolysis metabolism, protein biosynthesis, and gut microbiota metabolism. PF can also decrease bile acid metabolism. These findings indicate that different fiber diet may cause differences in the biofluid profile in rats. PMID:25541729

Plasma total antioxidant capacity is associated with dietary intake and plasma level of antioxidants in postmenopausal women.

PubMed

Wang, Ying; Yang, Meng; Lee, Sang-Gil; Davis, Catherine G; Kenny, Anne; Koo, Sung I; Chun, Ock K

2012-12-01

Increased plasma total antioxidant capacity (TAC) has been associated with a high consumption of fruits and vegetables. However, limited information is available on whether plasma TAC reflects the dietary intake of antioxidants and the levels of individual antioxidants in plasma. By using three different assays, the study aimed to determine if plasma TAC can effectively predict dietary intake of antioxidants and plasma antioxidant status. Forty overweight and apparently healthy postmenopausal women were recruited. Seven-day food records and 12-h fasting blood samples were collected for dietary and plasma antioxidant assessments. Plasma TAC was determined by vitamin C equivalent antioxidant capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly correlated with FRAP (r=0.79, P<.01) and moderately correlated with ORAC (r=0.34, P<.05). Pearson correlation analyses showed that plasma TAC values by VCEAC and ORAC had positive correlation with plasma uric acid (r=0.56 for VCEAC; r=0.49 for ORAC) and total phenolics (r=0.63 for VCEAC; r=0.36 for ORAC). However, TAC measured by FRAP was correlated only with uric acid (r=0.69). After multivariate adjustment, plasma TAC determined by VCEAC was positively associated with dietary intakes of γ-tocopherol (P<.001), β-carotene (P<.05), anthocyanidins (P<.05), flavones (P<.05), proanthocyanidins (P<.01) and TAC (P<.05), as well as with plasma total phenolics (P<.05), α-tocopherol (P<.001), β-cryptoxanthin (P<.05) and uric acid (P<.05). The findings indicate that plasma TAC measured by VCEAC reflects both dietary and plasma antioxidants and represents more closely the plasma antioxidant levels than ORAC and FRAP. Copyright © 2012 Elsevier Inc. All rights reserved.

Normal postprandial nonesterified fatty acid uptake in muscles despite increased circulating fatty acids in type 2 diabetes.

PubMed

Labbé, Sébastien M; Croteau, Etienne; Grenier-Larouche, Thomas; Frisch, Frédérique; Ouellet, René; Langlois, Réjean; Guérin, Brigitte; Turcotte, Eric E; Carpentier, André C

2011-02-01

Postprandial plasma nonesterified fatty acid (NEFA) appearance is increased in type 2 diabetes. Our objective was to determine whether skeletal muscle uptake of plasma NEFA is abnormal during the postprandial state in type 2 diabetes. Thigh muscle blood flow and oxidative metabolism indexes and NEFA uptake were determined using positron emission tomography coupled with computed tomography (PET/CT) with [(11)C]acetate and 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid ((18)FTHA) in seven healthy control subjects (CON) and seven subjects with type 2 diabetes during continuous oral intake of a liquid meal to achieve steady postprandial NEFA levels with insulin infusion to maintain similar plasma glucose levels in both groups. In the postprandial state, plasma NEFA level was higher in type 2 diabetic subjects versus CON (P < 0.01), whereas plasma glucose was at the same level in both groups. Muscle NEFA fractional extraction and blood flow index levels were 56% (P < 0.05) and 24% (P = 0.27) lower in type 2 diabetes, respectively. However, muscle NEFA uptake was similar to that of CON (quadriceps femoris [QF] 1.47 ± 0.23 vs. 1.37 ± 0.24 nmol·g(-1)·min(-1), P = 0.77; biceps femoris [BF] 1.54 ± 0.26 vs. 1.46 ± 0.28 nmol·g(-1)·min(-1), P = 0.85). Muscle oxidative metabolism was similar in both groups. Muscle NEFA fractional extraction and blood flow index were strongly and positively correlated (r = 0.79, P < 0.005). Postprandial muscle NEFA uptake is normal despite elevated systemic NEFA levels and acute normalization of plasma glucose in type 2 diabetes. Lower postprandial muscle blood flow with resulting reduction in muscle NEFA fractional extraction may explain this phenomenon.

Repaglinide has more beneficial effect on cardiovascular risk factors than glimepiride: data from meal-test study.

PubMed

Rizzo, M R; Barbieri, M; Grella, R; Passariello, N; Paolisso, G

2005-06-01

Aim our study is to compare the effects of repaglinide vs glimepiride administration on cardiovascular risk factors after meal test. Thus, after 2 weeks washout period, a 3-month randomised, cross-over parallel group trial of repaglinide (1 mg x 2/day) vs glimepiride (2 mg/day) in 14 patients with type 2 diabetes "naive" on diet treatment was made. Both treatments significantly declined plasma glucose, total-cholesterol, LDL-cholesterol, triglycerides, PAI-1, PAP levels and increased HDL-cholesterol. Lowering in plasma PAI-1 and PAP levels was significantly greater in repaglinide group. Furthermore, repaglinide administration resulted in a significant decrease in fasting plasma free fatty acids, fibrinogen, thrombin-antithrombin complex and reaction product of malondialdehyde with thiobarbituric acid (TBARS) levels, in absence of significant difference in fasting plasma insulin levels. Decrease in plasma TBARS levels correlated with the decrease in Plasminogen Activator Inhibitor-1 (r = 0.72; P < 0.003) and free fatty acids concentrations (r = 0.62; P < 0.01). Analysis of the insulin and glucose concentrations throughout the meal test revealed that AUC for glucose (758 +/- 19 vs 780 +/- 28 mg/Lxmin; P = 0.02) was significantly lower after repaglinide than glimepiride administration despite similar AUC for insulin (2327 +/- 269 vs 2148 +/- 292 mU/Lxmin; P = 0.105). At time 120' of meal test, repaglinide vs glimepiride administration was associated with a significant decline in plasma triglycerides, free fatty acids, fibrinogen, Plasminogen Activator Inhibitor-1, plasmin-alpha(2)-antiplasmin complex, thrombin-antithrombin complex, TBARS levels and increase in plasma HDL-cholesterol levels. In repaglinide group a negative correlation between insulin secretion during 1st phase of meal-test and plasma TBARS levels (r = -0.55; P < 0.03) at time 120' was found. Such correlation was lost after adjusting for changes in postprandial hyperglycaemia (r = -0.48; P < 0.09). In conclusion, our results support the hypothesis that repaglinide is more efficient than glimepiride on controlling for postprandial glucose excursion and may have beneficial effect on reducing cardiovascular risk factors.

Reduced Plasma Nonesterified Fatty Acid Levels and the Advent of an Acute Lung Injury in Mice after Intravenous or Enteral Oleic Acid Administration

PubMed Central

Gonçalves de Albuquerque, Cassiano Felippe; Burth, Patrícia; Younes Ibrahim, Mauricio; Garcia, Diogo Gomes; Bozza, Patrícia Torres; Castro Faria Neto, Hugo Caire; Castro Faria, Mauro Velho

2012-01-01

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets. PMID:22529526

Reduced plasma nonesterified fatty acid levels and the advent of an acute lung injury in mice after intravenous or enteral oleic acid administration.

PubMed

Gonçalves de Albuquerque, Cassiano Felippe; Burth, Patrícia; Younes Ibrahim, Mauricio; Garcia, Diogo Gomes; Bozza, Patrícia Torres; Castro Faria Neto, Hugo Caire; Castro Faria, Mauro Velho

2012-01-01

Although exerting valuable functions in living organisms, nonesterified fatty acids (NEFAs) can be toxic to cells. Increased blood concentration of oleic acid (OLA) and other fatty acids is detected in many pathological conditions. In sepsis and leptospirosis, high plasma levels of NEFA and low albumin concentrations are correlated to the disease severity. Surprisingly, 24 h after intravenous or intragastric administration of OLA, main NEFA levels (OLA inclusive) were dose dependently decreased. However, lung injury was detected in intravenously treated mice, and highest dose killed all mice. When administered by the enteral route, OLA was not toxic in any tested conditions. Results indicate that OLA has important regulatory properties on fatty acid metabolism, possibly lowering circulating fatty acid through activation of peroxisome proliferator-activated receptors. The significant reduction in blood NEFA levels detected after OLA enteral administration can contribute to the already known health benefits brought about by unsaturated-fatty-acid-enriched diets.

Optimisation of the dosage of tranexamic acid in trauma patients with population pharmacokinetic analysis.

PubMed

Grassin-Delyle, S; Theusinger, O M; Albrecht, R; Mueller, S; Spahn, D R; Urien, S; Stein, P

2018-06-01

Tranexamic acid is used both pre-hospital and in-hospital as an antifibrinolytic drug to treat or prevent hyperfibrinolysis in trauma patients; dosing, however, remains empirical. We aimed to measure plasma levels of tranexamic acid in patients receiving pre-hospital anti-hyperfibrinolytic therapy and to build a population pharmacokinetic model to propose an optimised dosing regimen. Seventy-three trauma patients were enrolled and each received tranexamic acid 1 g intravenously pre-hospital. A blood sample was drawn after arrival in the emergency department, and we measured the plasma tranexamic acid concentration using liquid chromatography-mass spectrometry, and modelled the data using non-linear mixed effect modelling. Tranexamic acid was administered at a median (IQR [range]) time of 43 (30-55 [5-135]) min after trauma. Plasma tranexamic acid levels were determined on arrival at hospital, 57 (43-70 [20-148]) min after pre-hospital administration of the drug. The measured concentration was 28.7 (21.5-38.5 [8.7-89.0]) μg.ml -1 . Our subjects had sustained severe trauma; injury severity score 20 (16-29 [5-75]), including penetrating injury in 2.8% and isolated traumatic brain injury in 19.7%. The pharmacokinetics were ascribed a two-compartment open model with body-weight as the main covariate. As tranexamic acid concentrations may fall below therapeutic levels during initial hospital treatment, we propose additional dosing schemes to maintain a specific target blood concentration for as long as required. This is the first study to investigate plasma level and pharmacokinetics of tranexamic acid after pre-hospital administration in trauma patients. Our proposed dosing regimen could be used in subsequent clinical trials to better study efficacy and tolerance profiles with controlled blood concentrations. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

Meal composition and plasma amino acid ratios: Effect of various proteins or carbohydrates, and of various protein concentrations

NASA Technical Reports Server (NTRS)

Yokogoshi, Hidehiko; Wurtman, Richard J.

1986-01-01

The effects of meals containing various proteins and carbohydrates, and of those containing various proportions of protein (0 percent to 20 percent of a meal, by weight) or of carbohydrate (0 percent to 75 percent), on plasma levels of certain large neutral amino acids (LNAA) in rats previously fasted for 19 hours were examined. Also the plasma tryptophan ratios (the ratio of the plasma trytophan concentration to the summed concentrations of the other large neutral amino acids) and other plasma amino acid ratios were calculated. (The plasma tryptophan ratio has been shown to determine brain tryptophan levels and, thereby, to affect the synthesis and release of the neurotransmitter serotonin). A meal containing 70 percent to 75 percent of an insulin-secreting carbohydrate (dextrose or dextrin) increased plasma insulin levels and the tryptophan ratio; those containing 0 percent or 25 percent carbohydrate failed to do so. Addition of as little as 5 percent casein to a 70 percent carbohydrate meal fully blocked the increase in the plasma tryptophan ratio without affecting the secretion of insulin - probably by contributing much larger quantities of the other LNAA than of tryptophan to the blood. Dietary proteins differed in their ability to suppress the carbohydrate-induced rise in the plasma tryptophan ratio. Addition of 10 percent casein, peanut meal, or gelatin fully blocked this increase, but lactalbumin failed to do so, and egg white did so only partially. (Consumption of the 10 percent gelatin meal also produced a major reduction in the plasma tyrosine ratio, and may thereby have affected brain tyrosine levels and catecholamine synthesis.) These observations suggest that serotonin-releasing neurons in brains of fasted rats are capable of distinguishing (by their metabolic effects) between meals poor in protein but rich in carbohydrates that elicit insulin secretion, and all other meals. The changes in brain serotonin caused by carbohydrate-rich, protein-poor meals may affect subsequent food choice and various serotonin-mediated behaviors.

Improved plasma amino acids pattern following 12 months of supplemented low-protein diet in peritoneal dialysis patients.

PubMed

Jiang, Na; Qian, Jiaqi; Lin, Aiwu; Fang, Wei; Cao, Liou; Wang, Qin; Ni, Zhaohui; Lindholm, Bengt; Axelsson, Jonas; Yao, Qiang

2010-07-01

Decreased plasma essential amino acid (EAA) levels, increased nonessential amino acid (NEAA) levels, and low EAA to NEAA ratio (E/NEAA) are common in peritoneal dialysis (PD) patients and may impact uremic complications. In the present study, we investigate the impact of keto acids-supplemented low-protein (sLP) diet on plasma amino acids (AAs) patterns in stable PD patients. This is a supplemental analysis of a previously published prospective and randomized trial. Thirty-nine PD patients selected from the original population were divided to receive either low (LP: 0.6-0.8 g/kg ideal body weight [IBW]/d, n = 13), keto acids-supplemented low- (sLP: 0.6-0.8 g/kg IBW/d + 0.12 g/kg IBW/d of keto acids, n = 12), or high- (HP: 1.0-1.2 g/kg IBW/d, n = 14) protein diets and followed for 1 year. Plasma AA patterns were assessed at baseline and 12 months using high-performance liquid chromatography. Whereas there were no significant differences between the three groups at baseline, following 12 months, the E/NEAA had increased significantly in group sLP (0.58 +/- 0.16 to 0.83 +/- 0.20, p < 0.05), but was not different in either LP (0.62 +/- 0.20 to 0.72 +/- 0.13, p = ns) or HP (0.66 +/- 0.14 to 0.74 +/- 0.12, p = ns) group. This change in E/NEAA in group sLP was due to a significant decrease in NEAA concomitantly with maintained EAA levels, whereas in the other two groups, neither EAA nor NEAA changed significantly. A low-protein diet supplemented with keto acids significantly improved the pattern of plasma AA in prevalent PD patients.

Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease

PubMed Central

Kawanaka, Miwa; Nishino, Ken; Oka, Takahito; Urata, Noriyo; Nakamura, Jun; Suehiro, Mitsuhiko; Kawamoto, Hirofumi; Chiba, Yasutaka; Yamada, Gotaro

2015-01-01

Objective Amino acid imbalance is often found in patients with cirrhosis, and this imbalance is associated with insulin resistance. However, the mechanism underlying the relationship between amino acid imbalance and insulin resistance remains unclear. We evaluated serum amino acid concentrations in patients with nonalcoholic fatty liver disease to determine if any of the levels of amino acids were associated with the biochemical markers and fibrosis stage of nonalcoholic steatohepatitis (NASH). Methods In 137 patients with nonalcoholic fatty liver disease who underwent liver biopsy, plasma levels of branched-chain amino acid (BCAA), tyrosine (Tyr), and the BCAA-to-Tyr ratio values were determined using mass spectroscopy. These values were then assessed for associations with fibrosis stage, anthropometric markers (age, sex, and body mass index), biochemical markers (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, albumin, platelet count, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and glycosylated hemoglobin), and relevant disease-specific biomarkers (homeostasis model assessment of insulin resistance [HOMA-IR], serum iron, ferritin, leptin, adiponectin, high-sensitivity C-reactive protein, and hyaluronic acid). Results Serum albumin levels, plasma BCAA levels, and BCAA-to-Tyr ratio values were negatively associated with the fibrosis stage. In contrast, Tyr levels increased with increasing fibrotic staging. Tyr levels were also correlated with HOMA-IR results. Conclusion Plasma BCAA levels in patients with NASH decreased with increasing liver fibrosis, while Tyr levels increased with increasing fibrotic stage. These results suggest that amino acid imbalance and insulin resistance are intimately involved in a complex pathogenic mechanism for NASH. PMID:26082668

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.

Plasma homovanillic acid in schizophrenics: supportive evidence for the two-subtype hypothesis.

PubMed

Chen, T Y; Lee, C F; Lung, F W; Lee, T C; Lin, W L; Hu, W H; Yeh, E K; Chang, W H

1989-06-01

Plasma levels of homovanillic acid (pHVA), a major metabolite of dopamine (DA), were measured in a group of 51 schizophrenic inpatients before and during 6 weeks of neuroleptic treatment. Steady-state plasma drug concentrations were monitored in parallel with pHVA. Good responders (n = 22) had higher pretreatment pHVA levels as compared to poor responders (n = 22). Differential pHVA changes during neuroleptic treatment were also found between each group. The two groups did not differ significantly in terms of age, duration of illness, severity of presenting symptoms, neuroleptic, dose, or plasma drug concentration. Two hypothetical subtypes in the group of schizophrenics were proposed.

Ursolic acid and luteolin-7-glucoside improve lipid profiles and increase liver glycogen content through glycogen synthase kinase-3.

PubMed

Azevedo, Marisa F; Camsari, Cagri; Sá, Carla M; Lima, Cristovao F; Fernandes-Ferreira, Manuel; Pereira-Wilson, Cristina

2010-06-01

In the present study, two phytochemicals - ursolic acid (UA) and luteolin-7-glucoside (L7G) - were assessed in vivo in healthy rats regarding effects on plasma glucose and lipid profile (total cholesterol, HDL and LDL), as well as liver glycogen content, in view of their importance in the aetiology of diabetes and associated complications. Both UA and L7G significantly decreased plasma glucose concentration. UA also significantly increased liver glycogen levels accompanied by phosphorylation of glycogen synthase kinase-3 (GSK3). The increase in glycogen deposition induced by UA (mediated by GSK3) could have contributed to the lower plasma glucose levels observed. Both compounds significantly lowered total plasma cholesterol and low-density lipoprotein levels, and, in addition, UA increased plasma high-density lipoprotein levels. Our results show that UA particularly may be useful in preventable strategies for people at risk of developing diabetes and associated cardiovascular complications by improving plasma glucose levels and lipid profile, as well as by promoting liver glycogen deposition.

Variation in plasma lipids during the reproductive cycle of male and female desert tortoises, Gopherus agassizii.

PubMed

Lance, Valentine A; Place, Allen R; Grumbles, Janice S; Rostal, David C

2002-12-01

Plasma triacylglycerol, phospholipid, cholesterol, cholesterol esters, fatty acids, and total lipids were measured in 30 female and 20 male desert tortoises (Gopherus agassizii) during the annual reproductive cycle in the eastern Mojave desert, Nevada. Blood samples were collected at monthly intervals from April to October. All lipid fractions, with the exception of free fatty acids, were significantly higher in female plasma than in male plasma in all months of the year. In contrast, free fatty acids were higher in male plasma than in female plasma in all months. The seasonal pattern in estradiol secretion mirrored that of triacylglycerol, phospholipid, cholesterol, and total lipid, all of which showed a significant correlation with the hormone. Estradiol and the vitellogenesis-associated lipids were all significantly higher in August, September, October, and April than in June. The seasonal variation in cholesterol ester levels in females did not correlate with any of the reproductive events and did not appear to be involved in yolk precursor formation. Total lipid in males showed a negative correlation with testosterone and spermatogenesis. Individual fatty acids in the June and August samples (at the highest and lowest estradiol levels) were compared in male and female plasma. The percent of C18:3n3, C18:2n6, C18:1n9, C20:5n3, and C22:5 were significantly higher in the June female plasma sample than in the August sample. Docosahexanoic (C22:6n3) acid was barely detectable in female plasma in either month. Copyright 2002 Wiley-Liss, Inc.

Effect of DHA on plasma fatty acid availability and oxidative stress during training season and football exercise.

PubMed

Martorell, Miquel; Capó, Xavier; Sureda, Antoni; Batle, Joan M; Llompart, Isabel; Argelich, Emma; Tur, Josep A; Pons, Antoni

2014-08-01

The aim was to determine the effects of a diet supplemented with 1.14 g per day of docosahexaenoic acid (DHA) for eight weeks on the plasma oxidative balance and anti-inflammatory markers after training and acute exercise. Fifteen volunteer male football players were randomly assigned to placebo or experimental and supplemented groups. Blood samples were taken under resting conditions at the beginning and after eight weeks of training under resting and post-exercise conditions. The experimental beverage increased the plasma DHA availability in non-esterified fatty acids (NEFAs) and triglyceride fatty acids (TGFAs) and increased the polyunsaturated fatty acid (PUFA) fraction of NEFAs but had no effects on the biomarkers for oxidative balance in plasma. During training, plasma protein markers of oxidative damage, the haemolysis degree and the antioxidant enzyme activities increased, but did not affect lipid oxidative damage. Training season and DHA influenced the circulating levels of prostaglandin E2 (PGE2). Acute exercise did not alter the basal levels of plasma markers for oxidative and nitrosative damage of proteins and lipids, and the antioxidant enzyme activities, although DHA-diet supplementation significantly increased the PGE2 in plasma after acute exercise. In conclusion, the training season and acute exercise, but not the DHA diet supplementation, altered the pattern of plasma oxidative damage, as the antioxidant system proved sufficient to prevent the oxidative damage induced by the acute exercise in well-trained footballers. The DHA-diet supplementation increased the prostaglandin PGE2 plasma evidencing anti-inflammatory effects of DHA to control inflammation after acute exercise.

Effects of acute and repeated oral doses of D-tagatose on plasma uric acid in normal and diabetic humans.

PubMed

Saunders, J P; Donner, T W; Sadler, J H; Levin, G V; Makris, N G

1999-04-01

D-tagatose, a stereoisomer of D-fructose, is a naturally occurring ketohexose proposed for use as a low-calorie bulk sweetener. Ingested D-tagatose appears to be poorly absorbed. The absorbed portion is metabolized in the liver by a pathway similar to that of D-fructose. The main purpose of this study was to determine if acute or repeated oral doses of D-tagatose would cause elevations in plasma uric acid (as is seen with fructose) in normal humans and Type 2 diabetics. In addition, effects of subchronic D-tagatose ingestion on fasting plasma phosphorus, magnesium, lipids, and glucose homeostasis were studied. Eight normal subjects and eight subjects with Type 2 diabetes participated in this two-phase study. Each group was comprised of four males and four females. In the first phase, all subjects were given separate 75 g 3-h oral glucose and D-tagatose tolerance tests. Uric acid, phosphorus, and magnesium were determined in blood samples collected from each subject at 0, 30, 60, 120, and 180 min after dose. In the 8-week phase of the study, the normals were randomly placed into two groups which received 75 g of either D-tagatose or sucrose (25 g with each meal) daily for 8 weeks. The diabetics were randomized into two groups which received either 75 g D-tagatose or no supplements of sugar daily for 8 weeks. Uric acid, phosphorus, magnesium, lipids, glycosylated hemoglobin, glucose, and insulin were determined in fasting blood plasma of all subjects at baseline (time zero) and biweekly over the 8 weeks. The 8-week test did not demonstrate an increase in fasting plasma uric acid in response to the daily intake of D-tagatose. However, a transient increase of plasma uric acid levels was observed after single doses of 75 g of D-tagatose in the tolerance test. Plasma uric acid levels were found to rise and peak at 60 min after such dosing. No clinical relevance was attributed to this treatment-related effect because excursions of plasma uric acid levels above the normal range were small and were of short duration. Consistent with earlier observations on fructose, the increase of plasma uric acid was associated with a slight decrease of plasma phosphorus and a slight increase of magnesium. The daily ingestion of D-tagatose for 8 weeks had no effect on fasting plasma magnesium, phosphorus, cholesterol, triglycerides, glycosylated hemoglobin, glucose, and insulin levels. The ingestion of three 25-g doses per day for a period of 8 weeks resulted in varying amounts of flatulence in seven of the eight subjects, and some degree of diarrhea in six subjects. D-tagatose holds promise as a sweetener with no adverse clinical effects observed in these studies. Copyright 1999 Academic Press.

Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study.

PubMed

Jørgenrud, Benedicte; Stene, Lars C; Tapia, German; Bøås, Håkon; Pepaj, Milaim; Berg, Jens P; Thorsby, Per M; Orešič, Matej; Hyötyläinen, Tuulia; Rønningen, Kjersti S

2017-03-01

The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes. Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites. Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age. Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Factors contributing to the resistivity of a higher casein diet against choline deficiency-induced hyperhomocysteinemia in rats.

PubMed

Liu, Yi-qun; Liu, Ying; Morita, Tatsuya; Mori, Makoto; Sugiyama, Kimio

2012-01-01

The mechanism by which feeding a higher casein diet results in resistance to choline deprivation-induced hyperhomocysteinemia was investigated in rats. Plasma homocysteine concentration was significantly lower in rats fed a 30% casein diet (30C) than in rats fed a 10% casein diet (10C). Choline deprivation did not enhance plasma homocysteine concentration in rats fed 30C, while it significantly enhanced plasma homocysteine concentration in rats fed 10C. The choline deprivation-induced enhancement of plasma homocysteine concentration in rats fed 10C was significantly suppressed by methionine supplementation in a dose-dependent manner in the range of 0.1 to 0.3%, but the suppressive effect of methionine became smaller with an increase in supplementation level in the range of 0.3 to 0.5%. At a 0.5% supplementation level, methionine did not exhibit any suppressive effect on choline deprivation-induced hyperhomocysteinemia. The higher plasma homocysteine concentration in rats fed choline-deprived 10C+0.5% methionine was significantly decreased by concurrent supplementation with 0.32% glycine+0.94% serine to the level of rats fed 10C. Raising dietary total amino acid level by adding 3.61% branched-chain amino acids (BCAA)+4.5% acidic amino acids (AAA) to choline-deprived 10C+0.5% methionine+0.32% glycine+0.94% serine resulted in a further decrease in plasma homocysteine concentration to a level lower than the level in rats fed 10C. Choline deprivation-induced increases in hepatic S-adenosylhomocysteine and homocysteine concentrations were significantly suppressed by supplementation with glycine+serine and further suppressed by BCAA+AAA. Hepatic cystathionine β-synthase activity and its gene expression were significantly increased by BCAA+AAA. Hepatic triglyceride concentration changed in a manner similar to that of plasma homocysteine concentration. The results indicate that there are at least three factors contributing to the resistivity of rats fed a higher casein diet (30C) to choline deprivation-induced hyperhomocysteinemia, i.e., higher intake of methionine, higher intake of glycine and serine, and higher intake of other amino acids such as BCAA and AAA.

Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

PubMed

Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Sodium Phenylbutyrate Decreases Plasma Branched-Chain Amino Acids in Patients with Urea Cycle Disorders

PubMed Central

Burrage, Lindsay C.; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H.; Nagamani, Sandesh CS.

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, they could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. PMID:25042691

Fatty acid composition of plasma lipids and erythrocyte membranes during simulated extravehicular activity

NASA Astrophysics Data System (ADS)

Skedina, M. A.; Katuntsev, V. P.; Buravkova, L. B.; Naidina, V. P.

Ten subjects (from 27 to 41 years) have been participated in 32 experiments. They were decompressed from ground level to 40-35 kPa in altitude chamber when breathed 100% oxygen by mask and performed repeated cycles of exercises (3.0 Kcal/min). The intervals between decompressions were 3-5 days. Plasma lipid and erythrocyte membrane fatty acid composition was evaluated in the fasting venous blood before and immediately after hypobaric exposure. There were 7 cases decompression sickness (DCS). Venous gas bubbles (GB) were detected in 27 cases (84.4%). Any significant changes in the fatty acid composition of erythrocyte membranes and plasma didn't practically induce after the first decompression. However, by the beginning of the second decompression the total lipid level in erythrocyte membranes decreased from 54.6 mg% to 40.4 mg% in group with DCS symptoms and from 51.2 mg% to 35.2 mg% (p < 0.05) without DCS symptoms. In group with DCS symptoms a tendency to increased level of saturated fatty acids in erythrocyte membranes (16:0, 18:0), the level of the polyunsaturated linoleic fatty acid (18:2) and arachidonic acid (20:4) tended to be decreased by the beginning of the second decompression. Insignificant changes in blood plasma fatty acid composition was observed in both groups. The obtained biochemical data that indicated the simulated extravehicular activity (EVA) condition is accompanied by the certain changes in the blood lipid metabolism, structural and functional state of erythrocyte membranes, which are reversible. The most pronounced changes are found in subjects with DCS symptoms.

Fatty acid composition of plasma lipids and erythrocyte membranes during simulated extravehicular activity.

PubMed

Skedina, M A; Katuntsev, V P; Buravkova, L B; Naidina, V P

1998-01-01

Ten subjects (from 27 to 41 years) have been participated in 32 experiments. They were decompressed from ground level to 40-35 kPa in altitude chamber when breathed 100% oxygen by mask and performed repeated cycles of exercises (3.0 Kcal/min). The intervals between decompressions were 3-5 days. Plasma lipid and erythrocyte membrane fatty acid composition was evaluated in the fasting venous blood before and immediately after hypobaric exposure. There were 7 cases decompression sickness (DCS). Venous gas bubbles (GB) were detected in 27 cases (84.4%). Any significant changes in the fatty acid composition of erythrocyte membranes and plasma didn't practically induce after the first decompression. However, by the beginning of the second decompression the total lipid level in erythrocyte membranes decreased from 54.6 mg% to 40.4 mg% in group with DCS symptoms and from 51.2 mg% to 35.2 mg% (p<0.05) without DCS symptoms. In group with DCS symptoms a tendency to increased level of saturated fatty acids in erythrocyte membranes (16:0, 18:0), the level of the polyunsaturated linoleic fatty acid (18:2) and arachidonic acid (20:4) tended to be decreased by the beginning of the second decompression. Insignificant changes in blood plasma fatty acid composition was observed in both groups. The obtained biochemical data that indicated the simulated extravehicular activity (EVA) condition is accompanied by the certain changes in the blood lipid metabolism, structural and functional state of erythrocyte membranes, which are reversible. The most pronounced changes are found in subjects with DCS symptoms.

Plasma lathosterol as a screening test for bile acid malabsorption due to ileal resection: correlation with 75SeHCAT test and faecal bile acid excretion.

PubMed

Färkkilä, M A; Kairemo, K J; Taavitsainen, M J; Strandberg, T A; Miettinen, T A

1996-04-01

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2. Plasma lathosterols and other non-cholesterol sterols were determined by GLC. Faecal bile acids were measured by GLC, and SeHCAT retention times by gamma camera. The study subjects were divided into two groups according to the degree of bile acid malabsorption: controls (faecal bile acids < 10 mg day-1 kg-1, n = 9) and bile acid malabsorption (faecal bile acids > 10 mg day-1 kg-1, n = 13). 3. Faecal bile acid excretion was 5.9 +/- 1.0 mg day-1 kg-1 in control subjects and 45.7 +/- 6.1 mg day-1 kg-1 in the bile acid malabsorption group. The biological half-life of 75SeHCAT (T1/2) was 95.6 +/- 16.3 h and 14.1 +/- 4.1 h, respectively. Plasma lathosterol levels were significantly elevated in patients with bile acid malabsorption (742 +/- 84 micrograms/ml compared with 400 +/- 59 micrograms/ml in control subjects) and correlated closely with faecal bile acid levels (r = 0.779, P < 0.001), with 75SeHCAT T1/2 (r = -0.524, P < 0.05) and with Schilling test (r = -0.591, P < 0.05). Significant correlations were also obtained for delta 8-cholestenol with faecal bile acids (r = 0.784, P < 0.001) and 75SeHCAT (r = -0.505, P < 0.05). The biological half-life of SeHCAT correlated with faecal bile acid excretion (r = -0.702, P < 0.001). Using mean+2 SD of lathosterol (In micrograms/ml cholesterol) as a cut-off value and 10 mg day-1 kg-1 as the upper limit for faecal bile acid excretion, the test gives 100% sensitivity and 82% specificity for plasma lathosterol determination to detect bile acid malabsorption. 4. The results indicate that both the 75SeHCAT test and plasma lathosterol detect bile acid malabsorption in patients with ileal resections for Crohn's disease. However, plasma lathosterol is a simpler and less expensive method.

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.

Insulin receptor substrate-2 gene variants in subjects with metabolic syndrome: association with plasma monounsaturated and n-3 polyunsaturated fatty acid levels and insulin resistance.

PubMed

Perez-Martinez, Pablo; Delgado-Lista, Javier; Garcia-Rios, Antonio; Tierney, Audrey C; Gulseth, Hanne L; Williams, Christine M; Karlström, Brita; Kieć-Wilk, Beata; Blaak, Ellen E; Helal, Olfa; Saris, Wim H M; Defoort, Catherine; Drevon, Christian A; Lovegrove, Julie A; Dembinska-Kieć, Aldona; Riserus, Ulf; Roche, Helen M; Lopez-Miranda, Jose

2012-02-01

Several insulin receptor substrate-2 (IRS-2) polymorphisms have been studied in relation to insulin resistance and type 2 diabetes. To examine whether the genetic variability at the IRS-2 gene locus was associated with the degree of insulin resistance and plasma fatty acid levels in metabolic syndrome (MetS) subjects. Insulin sensitivity, insulin secretion, glucose effectiveness, plasma fatty acid composition and three IRS-2 tag-single nucleotide polymorphisms (SNPs) were determined in 452 MetS subjects. Among subjects with the lowest level of monounsaturated (MUFA) (below the median), the rs2289046 A/A genotype was associated with lower glucose effectiveness (p<0.038), higher fasting insulin concentrations (p<0.028) and higher HOMA IR (p<0.038) as compared to subjects carrying the minor G-allele (A/G and G/G). In contrast, among subjects with the highest level of MUFA (above the median), the A/A genotype was associated with lower fasting insulin concentrations and HOMA-IR, whereas individuals carrying the G allele and with the highest level of ω-3 polyunsaturated fatty acids (above the median) showed lower fasting insulin (p<0.01) and HOMA-IR (p<0.02) as compared with A/A subjects. The rs2289046 polymorphism at the IRS2 gene locus may influence insulin sensitivity by interacting with certain plasma fatty acids in MetS subjects. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Amino acid homeostasis and signalling in mammalian cells and organisms

PubMed Central

Bröer, Angelika

2017-01-01

Cells have a constant turnover of proteins that recycle most amino acids over time. Net loss is mainly due to amino acid oxidation. Homeostasis is achieved through exchange of essential amino acids with non-essential amino acids and the transfer of amino groups from oxidised amino acids to amino acid biosynthesis. This homeostatic condition is maintained through an active mTORC1 complex. Under amino acid depletion, mTORC1 is inactivated. This increases the breakdown of cellular proteins through autophagy and reduces protein biosynthesis. The general control non-derepressable 2/ATF4 pathway may be activated in addition, resulting in transcription of genes involved in amino acid transport and biosynthesis of non-essential amino acids. Metabolism is autoregulated to minimise oxidation of amino acids. Systemic amino acid levels are also tightly regulated. Food intake briefly increases plasma amino acid levels, which stimulates insulin release and mTOR-dependent protein synthesis in muscle. Excess amino acids are oxidised, resulting in increased urea production. Short-term fasting does not result in depletion of plasma amino acids due to reduced protein synthesis and the onset of autophagy. Owing to the fact that half of all amino acids are essential, reduction in protein synthesis and amino acid oxidation are the only two measures to reduce amino acid demand. Long-term malnutrition causes depletion of plasma amino acids. The CNS appears to generate a protein-specific response upon amino acid depletion, resulting in avoidance of an inadequate diet. High protein levels, in contrast, contribute together with other nutrients to a reduction in food intake. PMID:28546457

UHPLC-Q-Orbitrap-HRMS-based global metabolomics reveal metabolome modifications in plasma of young women after cranberry juice consumption.

PubMed

Liu, Haiyan; Garrett, Timothy J; Su, Zhihua; Khoo, Christina; Gu, Liwei

2017-07-01

Plasma metabolome in young women following cranberry juice consumption were investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female college students, between 21 and 29 years old, were given either cranberry juice or apple juice for three days using a cross-over design. Plasma samples were collected before and after juice consumption. Plasma metabolomes were analyzed using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in young women, including both exogenous and endogenous metabolites, were altered following cranberry juice consumption. Cranberry juice caused increases of exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4-dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5-(trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid, hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma levels of endogenous metabolites including citramalic acid, aconitic acid, hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid, vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and glycerol 3-phosphate were increased in women following cranberry juice consumption. The metabolic differences and discriminant metabolites observed in this study may serve as biomarkers of cranberry juice consumption and explain its health promoting properties in human. Copyright © 2017 Elsevier Inc. All rights reserved.

Conversion of α-linolenic acid to long-chain omega-3 fatty acid derivatives and alterations of HDL density subfractions and plasma lipids with dietary polyunsaturated fatty acids in Monk parrots (Myiopsitta monachus).

PubMed

Petzinger, C; Larner, C; Heatley, J J; Bailey, C A; MacFarlane, R D; Bauer, J E

2014-04-01

The effect of α-linolenic acid from a flaxseed (FLX)-enriched diet on plasma lipid and fatty acid metabolism and possible atherosclerosis risk factors was studied in Monk parrots (Myiopsitta monachus). Twenty-four Monk parrots were randomly assigned to diets containing either 10% ground SUNs or 10% ground FLXs. Feed intake was calculated daily. Blood samples, body condition scores and body weights were obtained at -5 weeks, day 0, 7, 14, 28, 42 and 70. Plasma samples were analysed for total cholesterol, free cholesterol, triacylglycerols and lipoproteins. Phospholipid subfraction fatty acid profiles were determined. By day 70, the FLX group had significantly higher plasma phospholipid fatty acids including 18:3n-3 (α-linolenic acid), 20:5n-3 (eicosapentaenoic acid) and 22:6n-3 (docosahexaenoic acid). The sunflower group had significantly higher plasma phospholipid levels of 20:4n-6 (arachidonic acid). By day 70, the high-density lipoprotein (HDL) peak shifted resulting in significantly different HDL peak densities between the two experimental groups (1.097 g/ml FLX group and 1.095 g/ml SUN group, p = 0.028). The plasma fatty acid results indicate that Monk parrots can readily convert α-linolenic acid to the long-chain omega-3 derivatives including docosahexaenoic acid and reduce 20:4n-6 accumulation in plasma phospholipids. The reason for a shift in the HDL peak density is unknown at this time. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

Ethnicity, plasma phospholipid fatty acid composition and inflammatory/endothelial activation biomarkers in the Multi-Ethnic Study of Atherosclerosis (MESA).

PubMed

Steffen, B T; Steffen, L M; Tracy, R; Siscovick, D; Jacobs, D; Liu, K; He, K; Hanson, N Q; Nettleton, J A; Tsai, M Y

2012-05-01

It has been recognized that certain long-chain polyunsaturated fatty acids (LC-PUFAs) are involved in inflammation and its resolution. It has also been shown that ethnicity may be a factor in affecting systemic inflammation, and limited evidence suggests it may influence plasma LC-PUFA composition. Given the links among these three factors, we aim to determine ethnicity-based differences in plasma LC-PUFA composition among White, Black, Hispanic and Chinese participants, and whether such differences contribute to variations in markers of inflammation and endothelial activation in a sub-cohort of the Multi-Ethnic Study of Atherosclerosis (MESA). Plasma phospholipid LC-PUFAs levels (%) were determined in 2848 MESA participants using gas chromatography-flame ionization detection. Enzyme immunoassays determined inflammatory markers levels for high-sensitivity C-reactive protein (n=2848), interleukin-6 (n=2796), soluble tumor necrosis factor-α receptor type 1 (n=998), and endothelial activation markers soluble intercellular adhesion molecule-1 (n=1192) and soluble E-selectin (n=998). The modifying influence of ethnicity was tested by linear regression analysis. Chinese adults were found to have the highest mean levels of plasma eicosapentaenoic acid (EPA, 1.24%) and docosahexaenoic acid (DHA, 4.95%), and the lowest mean levels of γ-linolenic (0.10%), dihomo-γ-linolenic (DGLA, 2.96%) and arachidonic (10.72%) acids compared with the other ethnicities (all P ≤ 0.01). In contrast, Hispanics had the lowest mean levels of plasma EPA (0.70%) and DHA (3.49%), and the highest levels of DGLA (3.59%; all P ≤ 0.01). Significant differences in EPA and DHA among ethnicities were attenuated following adjustment for dietary non-fried fish and fish oil supplementation. Ethnicity did not modify the associations of LC-PUFAs with markers of inflammation or endothelial activation (all P (interaction)>0.05). The absence of a modifying effect of ethnicity indicates that the putative benefits of LC-PUFAs with respect to inflammation are pan-ethnic. Future longitudinal studies may elucidate the origin(s) of ethnicity-based differences in LC-PUFA composition and whether certain patterns, that is, high plasma levels of DGLA and low levels of EPA/DHA, contribute to inflammation-associated health outcomes.

Mangiferin Decreases Plasma Free Fatty Acids through Promoting Its Catabolism in Liver by Activation of AMPK

PubMed Central

Niu, Yucun; Li, Songtao; Na, Lixin; Feng, Rennan; Liu, Liyan; Li, Ying; Sun, Changhao

2012-01-01

Mangiferin has been shown to have the effect of improving dyslipidemia. Plasma free fatty acids (FFA) are closely associated with blood lipid metabolism as well as many diseases including metabolic syndrome. This study is to investigate whether mangiferin has effects on FFA metabolism in hyperlipidemic rats. Wistar rats were fed a high-fat diet and administered mangiferin simultaneously for 6 weeks. Mangiferin (50, 100, 150 mg/kg BW) decreased dose-dependently FFA and triglycerides (TG) levels in plasma, and their accumulations in liver, but increased the β-hydroxybutyrate levels in both plasma and liver of hyperlipidemic rats. HepG2 cells were treated with oleic acid (OA, 0.2 mmol/L) to simulate the condition of high level of plasma FFA in vitro, and were treated with different concentrations of mangiferin simultaneously for 24 h. We found that mangiferin significantly increased FFA uptake, significantly decreased intracellular FFA and TG accumulations in HepG2 cells. Mangiferin significantly increased AMP-activated protein kinase (AMPK) phosphorylation and its downstream proteins involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1), but significantly decreased acyl-CoA: diacylgycerol acyltransferase 2 (DGAT2) expression and acetyl-CoA carboxylase (ACC) activity by increasing its phosphorylation level in both in vivo and in vitro studies. Furthermore, these effects were reversed by Compound C, an AMPK inhibitor in HepG2 cells. For upstream of AMPK, mangiferin increased AMP/ATP ratio, but had no effect on LKB1 phosphorylation. In conclusion, mangiferin decreased plasma FFA levels through promoting FFA uptake and oxidation, inhibiting FFA and TG accumulations by regulating the key enzymes expression in liver through AMPK pathway. Therefore, mangiferin is a possible beneficial natural compound for metabolic syndrome by improving FFA metabolism. PMID:22292039

Polymorphisms of the TNF-α gene interact with plasma fatty acids on inflammatory biomarker profile: a population-based, cross-sectional study in São Paulo, Brazil.

PubMed

Oki, Erica; Norde, Marina N; Carioca, Antônio A F; Souza, José M P; Castro, Inar A; Marchioni, Dirce M L; Fisberg, Regina M; Rogero, Marcelo M

2017-06-01

The aim of the present study was to investigate the relationship of four TNF-α SNP with inflammatory biomarkers and plasma fatty acids (FA), and the interaction among them in a population-based, cross-sectional study in São Paulo, Brazil. A total of 281 subjects, aged >19 and <60 years, participated in a cross-sectional, population-based study performed in Brazil. The following SNP spanning the TNF-α gene were genotyped: -238G/A (rs361525), -308G/A (rs1800629), -857C/T (rs1799724) and -1031T/C (rs1799964). In all, eleven plasma inflammatory biomarkers and plasma FA profile were determined. To analyse the interaction between TNF-α SNP and plasma FA, a cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups used as outcome: inflammatory (INF) and non-inflammatory clusters. The -238A allele carriers had higher TNF-α (P=0·033), IL-6 (P=0·013), IL-1β (P=0·037), IL-12 (0·048) and IL-10 (P=0·010) than the GG genotype. The -308A allele carriers also had lower levels of plasma palmitoleic acid (P=0·009), oleic acid (P=0·039), total MUFA (P=0·014), stearoyl-CoA desaturase (SCD) activity index-16 (P=0·007), SCD-18 (P=0·020) and higher levels of PUFA (P=0·046) and DHA (P=0·044). Significant interactions modifying the risk of belonging to the INF cluster were observed with inflammatory cluster as outcome between -857C/T and plasma α-linolenic acid (P=0·026), and also between -308G/A and plasma stearic acid (P=0·044) and total SFA (P=0·040). Our study contributes to knowledge on TNF-α SNP and their association with inflammatory biomarker levels, plasma FA and the interaction among them, of particular interest for the Brazilian population.

Contrasting plasma free amino acid patterns in elite athletes: association with fatigue and infection

PubMed Central

Kingsbury, K. J.; Kay, L.; Hjelm, M.

1998-01-01

AIM: There is little information on the plasma free amino acid patterns of elite athletes against which fatigue and nutrition can be considered. Therefore the aim was to include analysis of this pattern in the medical screening of elite athletes during both especially intense and light training periods. METHODS: Plasma amino acid analysis was undertaken in three situations. (1) A medical screening service was offered to elite athletes during an intense training period before the 1992 Olympics. Screening included a blood haematological/biochemical profile and a microbial screen in athletes who presented with infection. The athletes were divided into three groups who differed in training fatigue and were considered separately. Group A (21 track and field athletes) had no lasting fatigue; group B (12 judo competitors) reported heavy fatigue at night but recovered overnight to continue training; group C (18 track and field athletes, one rower) had chronic fatigue and had been unable to train normally for at least several weeks. (2) Athletes from each group were further screened during a post- Olympic light training period. (3) Athletes who still had low amino acid levels during the light training period were reanalysed after three weeks of additional protein intake. RESULTS: (1) The pre-Olympics amino acid patterns were as follows. Group A had a normal amino acid pattern (glutamine 554 (25.2) micromol/l, histidine 79 (6.1) micromol/l, total amino acids 2839 (92.1) micromol/l); all results are means (SEM). By comparison, both groups B and C had decreased plasma glutamine (average 33%; p<0.001) with, especially in group B, decreased histidine, glucogenic, ketogenic, and branched chain amino acids (p<0.05 to p<0.001). None in group A, one in group B, but ten athletes in group C presented with infection: all 11 athletes had plasma glutamine levels of less than 450 micromol/l. No intergroup differences in haematological or other blood biochemical parameters, apart from a lower plasma creatine kinase activity in group C than in group B (p<0.05) and a low neutrophil to lymphocyte ratio in the athletes with viral infections (1.2 (0.17)), were found. (2) During post-Olympic light training, group A showed no significant amino acid changes. In contrast, group B recovered normal amino acid levels (glutamine 528 (41.4) micromol/l, histidine 76 (5.3) micromol/l, and total amino acids 2772 (165) micromol/l) (p<0.05 to p<0.001) to give a pattern comparable with that of group A, whereas, in group C, valine and threonine had increased (p<0.05), but glutamine (441 (24.5) micromol/l) and histidine (58 (5.3) micromol/l) remained low. Thus none in group A, two in group B, but ten (53%) in group C still had plasma glutamine levels below 450 micromol/l, including eight of the 11 athletes who had presented with infection. (3) With the additional protein intake, virtually all persisting low glutamine levels increased to above 500 micromol/l. Plasma glutamine rose to 592 (35.1) micromol/l and histidine to 86 (6.0) micromol/l. Total amino acids increased to 2761 (128) micromol/l (p<0.05 to p<0.001) and the amino acid pattern normalised. Six of the ten athletes on this protein intake returned to increased training within the three weeks. CONCLUSION: Analysis of these results provided contrasting plasma amino acid patterns: (a) a normal pattern in those without lasting fatigue; (b) marked but temporary changes in those with acute fatigue; (c) a persistent decrease in plasma amino acids, mainly glutamine, in those with chronic fatigue and infection, for which an inadequate protein intake appeared to be a factor. 


 PMID:9562160

Optimal dietary therapy of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

PubMed Central

Gillingham, Melanie B.; Connor, William E.; Matern, Dietrich; Rinaldo, Piero; Burlingame, Terry; Meeuws, Kaatje; Harding, Cary O.

2009-01-01

Current dietary therapy for long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) or trifunctional protein (TFP) deficiency consists of fasting avoidance, and limiting long-chain fatty acid (LCFA) intake. This study reports the relationship of dietary intake and metabolic control as measured by plasma acylcarnitine and organic acid profiles in 10 children with LCHAD or TFP deficiency followed for 1 year. Subjects consumed an average of 11% of caloric intake as dietary LCFA, 11% as MCT, 12% as protein, and 66% as carbohydrate. Plasma levels of hydroxypalmitoleic acid, hydroxyoleic, and hydroxylinoleic carnitine esters positively correlated with total LCFA intake and negatively correlated with MCT intake suggesting that as dietary intake of LCFA decreases and MCT intake increases, there is a corresponding decrease in plasma hydroxyacylcarnitines. There was no correlation between plasma acylcarnitines and level of carnitine supplementation. Dietary intake of fat-soluble vitamins E and K was deficient. Dietary intake and plasma levels of essential fatty acids, linoleic and linolenic acid, were deficient. On this dietary regimen, the majority of subjects were healthy with no episodes of metabolic decompensation. Our data suggest that an LCHAD or TFP-deficient patient should adhere to a diet providing age-appropriate protein and limited LCFA intake (10% of total energy) while providing 10–20% of energy as MCT and a daily multi-vitamin and mineral (MVM) supplement that includes all of the fat-soluble vitamins. The diet should be supplemented with vegetable oils as part of the 10% total LCFA intake to provide essential fatty acids. PMID:12809642

Increased oxidative stress in patients with amyotrophic lateral sclerosis and the effect of edaravone administration.

PubMed

Nagase, Midori; Yamamoto, Yorihiro; Miyazaki, Yusuke; Yoshino, Hiide

2016-05-01

Compared to age-matched healthy controls (n = 55), patients with amyotrophic lateral sclerosis (ALS) (n = 26) showed increased oxidative stress as indicated by a significantly increased percentage of oxidized coenzyme Q10 (%CoQ10) in total plasma coenzyme Q10, a significantly decreased level of plasma uric acid, and a significantly decreased percentage of polyunsaturated fatty acids in total plasma free fatty acids (FFA). Therefore, the efficacy of edaravone, a radical scavenger, in these ALS patients was examined. Among 26 ALS patients, 17 received edaravone (30 mg/day, one to four times a week) for at least 3 months, and 13 continued for 6 months. Changes in revised ALS functional rating scale (ALSFRS-R) were significantly smaller in these patients than in edaravone-untreated ALS patients (n = 19). Edaravone administration significantly reduced excursions of more than one standard deviation from the mean for plasma FFA levels and the contents of palmitoleic and oleic acids, plasma markers of tissue oxidative damage, in the satisfactory progress group (ΔALSFRS-R ≥ 0) as compared to the ingravescent group (ΔALSFRS-R < -5). Edaravone treatment increased plasma uric acid, suggesting that it is an effective scavenger of peroxynitrite. However, edaravone administration did not decrease %CoQ10. Therefore, combined treatment with agents such as coenzyme Q10 may further reduce oxidative stress in ALS patients.

Omega-3 and omega-6 Fatty acids in blood and breast tissue of high-risk women and association with atypical cytomorphology.

PubMed

Hidaka, Brandon H; Li, Shengqi; Harvey, Katherine E; Carlson, Susan E; Sullivan, Debra K; Kimler, Bruce F; Zalles, Carola M; Fabian, Carol J

2015-05-01

The ratio of omega-3 to omega-6 fatty acids, especially the long-chain eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) to arachidonic acid (AA) ratio, is inversely associated with breast cancer risk. We measured the association between cytologic atypia, a biomarker for short-term risk of breast cancer development, and omega-3 and omega-6 fatty acid intake and levels in blood and breast tissue. Blood and benign breast tissue, sampled by random periareolar fine-needle aspiration (RPFNA), was obtained from 70 women at elevated risk for breast cancer. Self-reported dietary intake was assessed by the NCI's Food Frequency Questionnaire. The fatty acid composition of five lipid compartments, red blood cell, plasma and breast phospholipids, and plasma and breast triaclyglycerides (TAG), was analyzed by gas chromatography as weight percent. Median daily intakes of EPA+DHA and total omega-3 fatty acids were 80 mg and 1.1 g, respectively. The median total omega-3:6 intake ratio was 1:10. Compared with women without atypia, those with cytologic atypia had lower total omega-3 fatty acids in red blood cell and plasma phospholipids and lower omega-3:6 ratios in plasma TAGs and breast TAGs (P < 0.05). The EPA+DHA:AA ratio in plasma TAGs was also lower among women with atypia. This is the first report of associations between tissue levels of omega-3 and omega-6 fatty acids and a reversible tissue biomarker of breast cancer risk. RPFNA cytomorphology could serve as a surrogate endpoint for breast cancer prevention trials of omega-3 fatty acid supplementation. ©2015 American Association for Cancer Research.

Plasma and semen ascorbic levels in spermatogenesis.

PubMed

Ebesunun, M O; Solademi, B A; Shittu, O B; Anetor, J I; Onuegbu, J A; Olisekodiaka, J M; Agbedana, E O; Onyeaghala, A A

2004-01-01

Conflicting reports on the mechanism of action of ascorbic acid level in male reproductive system exist and very little is known about the ascorbic acid status in Nigerian males with weak fertility. Ascorbate that accumulates preferentially in the testis, the lipid and lipoprotein levels were determined in the plasma of Nigerian males. Twenty-seven (27) male with inadequate spermatogenesis (36+/-1.0) years, with mean value of 15.6+/-6.90 million/cm3 sperm count and fourteen (14) controls (34+/-0.6) years, with mean value of 108.0+/-25.42 million/cm3 sperm count were selected for this study. The anthropometric indices were also determined. There were highly significant decreases in sperm cell count, percentage motility and percentage vitality (p<0.001) in each case, while percentage morphologically abnormal sperm cells was significantly elevated (p<0.001) compared with the control values. There were significant decreases in the seminal and plasma ascorbic acid concentrations (p<0.001) in the males who had inadequate spermatogenesis compared with the control values. The plasma total cholesterol (TC) and body mass index (BMI) were not significantly different from the corresponding control values, but the plasma low density lipoprotein (LDLC) (p<0.001) and triglyceride (TG)(p<0.01) concentrations were significantly increased in all the patients. While the plasma high density lipoprotein cholesterol (HDLC)(p<0.001) was significantly decreased compared with the controls. The plasma lipid and lipoprotein levels did not demonstrate any definite pattern with the sperm characteristics. The decreased semen ascorbate level may play a significant role in the reduced sperm characteristics in these patients.

The measurement of insulin-like growth factor 1 in sheep plasma.

PubMed

Bruce, L A; Atkinson, T; Hutchinson, J S; Shakespear, R A; MacRae, J C

1991-02-01

A method is described for the radioimmunoassay (RIA) of insulin-like growth factor 1 (IGF-1) in neutralised formic acid-ethanol extracts of sheep plasma. The ability of the acid-ethanol pretreatment to remove the IGF-1 binding proteins (BPs), which interfere in the assay has been examined. Comparative plasma IGF-1 concentrations determined by the method correlated closely (P less than 0.001) with corresponding values where BPs were removed by acid gel filtration. The method has been applied to studies in which sheep were given exogenous growth hormone and indicated that plasma IGF-1 levels respond rapidly to the onset and termination of treatment.

PCK1 expression is correlated with the plasma glucose level in the duck.

PubMed

Chen, L; Zeng, T; Li, G Q; Liu, R; Tian, Y; Li, Q H; Lu, L Z

2017-06-01

Phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1) is a key gene in gluconeogenesis and glyceroneogenesis. Although its functions have been extensively studied in mice, bats and humans, little is known in ducks. Here, PCK1 functions were studied using a duck domestication model and a 48-h fasting experiment. We found PCK1 expression significantly decreased in two breeds of domestic ducks (Jinyun Pockmark ducks and Cherry Valley ducks) as compared with wild ducks (Anas platyrhynchos). Simultaneously, plasma levels of glucose, triglycerides and free fatty acid in domestic ducks were lower than in wild ducks. When compared with fed ducks, the plasma triglyceride level was observed to be significantly decreased, while the glucose and free fatty acid levels remained constant in 48-h fasting ducks. The expression analysis of gluconeogenic genes revealed that fructose-1,6-bisphosphatase genes (FBP1 and FBP2) and the glucose-6-phosphatase gene (G6PC2) were not changed, whereas PCK1 was significantly upregulated. In addition, the reported regulators of PCK1, including forkhead box A2 (FOXA2) gene and orphan nuclear receptor NR4A family genes (NR4A1, NR4A2 and NR4A3), exhibited similar expression levels between 48-h fasting ducks and fed ducks, suggesting that PCK1 is not regulated by these genes in the duck under fasting conditions. In conclusion, PCK1 expression may affect plasma levels of glucose, triglycerides and free fatty acid during the duck domestication process. This work demonstrates for the first time in duck that PCK1 is a key gene in maintaining plasma glucose homeostasis during fasting and that the upregulated expression of PCK1 may be responsible for constant plasma free fatty acid level by the glyceroneogenesis process. © 2017 Stichting International Foundation for Animal Genetics.

Measurement of the diene conjugated form of linoleic acid in plasma by high performance liquid chromatography: a questionable non-invasive assay of free radical activity?

PubMed

Thompson, S; Smith, M T

1985-11-01

It has been previously reported that the main diene-conjugated fatty acid in human plasma is a non-oxygen containing linoleic acid isomer (PL-9, 11-LA'). It has also been proposed that this isomer can be used as a specific marker of free radical-mediated lipid peroxidation in humans. Here we report that the in vitro induction of lipid peroxidation in human and rat blood with either UV irradiation or phenylhydrazine failed to increase the plasma levels of this isomer. The induction of lipid peroxidation in vivo in rats pretreated with either phenylhydrazine or bromotrichloromethane also failed to increase the plasma levels of this isomer. These findings demonstrate that PL-9, 11-LA' cannot be used as an in vivo marker of free radical-mediated lipid peroxidation in rats and casts doubts on its validity as a specific marker in humans.

Apolipoprotein E isoforms 3/3 and 3/4 differentially interact with circulating stearic, palmitic, and oleic fatty acids and lipid levels in Alaskan Natives.

PubMed

Castellanos-Tapia, Lyssia; López-Alvarenga, Juan Carlos; Ebbesson, Sven O E; Ebbesson, Lars O E; Tejero, M Elizabeth

2015-04-01

Lifestyle changes in Alaskan Natives have been related to the increase of cardiovascular disease and metabolic syndrome in the last decades. Variation of the apolipoprotein E (Apo E) genotype may contribute to the diverse response to diet in lipid metabolism and influence the association between fatty acids in plasma and risk factors for cardiovascular disease. The aim of this investigation was to analyze the interaction between Apo E isoforms and plasma fatty acids, influencing phenotypes related to metabolic diseases in Alaskan Natives. A sample of 427 adult Siberian Yupik Alaskan Natives was included. Fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, Apo A1, and Apo B plasma concentrations were measured using reference methods. Concentrations of 13 fatty acids in fasting plasma were analyzed by gas chromatography, and Apo E variants were identified. Analyses of covariance were conducted to identify Apo E isoform and fatty acid main effects and multiplicative interactions. The means for body mass index and age were 26 ± 5.2 and 47 ± 1.5, respectively. Significant main effects were observed for variation in Apo E and different fatty acids influencing Apo B levels, triglycerides, and total cholesterol. Significant interactions were found between Apo E isoform and selected fatty acids influencing total cholesterol, triglycerides, and Apo B concentrations. In summary, Apo E3/3 and 3/4 isoforms had significant interactions with circulating levels of stearic, palmitic, oleic fatty acids, and phenotypes of lipid metabolism in Alaskan Natives. Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.

PubMed

Tanaka, Toshiko; Shen, Jian; Abecasis, Gonçalo R; Kisialiou, Aliaksei; Ordovas, Jose M; Guralnik, Jack M; Singleton, Andrew; Bandinelli, Stefania; Cherubini, Antonio; Arnett, Donna; Tsai, Michael Y; Ferrucci, Luigi

2009-01-01

Polyunsaturated fatty acids (PUFA) have a role in many physiological processes, including energy production, modulation of inflammation, and maintenance of cell membrane integrity. High plasma PUFA concentrations have been shown to have beneficial effects on cardiovascular disease and mortality. To identify genetic contributors of plasma PUFA concentrations, we conducted a genome-wide association study of plasma levels of six omega-3 and omega-6 fatty acids in 1,075 participants in the InCHIANTI study on aging. The strongest evidence for association was observed in a region of chromosome 11 that encodes three fatty acid desaturases (FADS1, FADS2, FADS3). The SNP with the most significant association was rs174537 near FADS1 in the analysis of arachidonic acid (AA; p = 5.95 x 10(-46)). Minor allele homozygotes had lower AA compared to the major allele homozygotes and rs174537 accounted for 18.6% of the additive variance in AA concentrations. This SNP was also associated with levels of eicosadienoic acid (EDA; p = 6.78 x 10(-9)) and eicosapentanoic acid (EPA; p = 1.07 x 10(-14)). Participants carrying the allele associated with higher AA, EDA, and EPA also had higher low-density lipoprotein (LDL-C) and total cholesterol levels. Outside the FADS gene cluster, the strongest region of association mapped to chromosome 6 in the region encoding an elongase of very long fatty acids 2 (ELOVL2). In this region, association was observed with EPA (rs953413; p = 1.1 x 10(-6)). The effects of rs174537 were confirmed in an independent sample of 1,076 subjects participating in the GOLDN study. The ELOVL2 SNP was associated with docosapentanoic and DHA but not with EPA in GOLDN. These findings show that polymorphisms of genes encoding enzymes in the metabolism of PUFA contribute to plasma concentrations of fatty acids.

Guanidinoacetic acid loading affects plasma γ-aminobutyric acid in healthy men.

PubMed

Ostojic, Sergej M; Stojanovic, Marko

2015-08-01

Guanidinoacetic acid (GAA), a precursor of creatine and an innovative dietary agent, activates γ-amino butyric acid (GABA) receptors yet clinical effects of dietary GAA on GABA metabolism are currently unknown. The main aim of this pilot research was to investigate whether GAA loading affected peripheral GABA homeostasis in healthy humans. Eight healthy male volunteers aged 22-25 years were randomized in a double-blind design to receive either GAA (three grams daily) or placebo by oral administration for 3 weeks. At baseline and after 3 weeks participants provided fasting blood samples for free plasma levels of GABA, GAA, creatine and glutamine. Following 3 weeks of intervention, plasma GABA level dropped significantly in participants receiving 3 g of GAA per day as compared to the placebo (P = 0.03). GAA loading significantly decreased plasma GABA by 88.8 nmol/L (95% confidence interval; 5.4-172.1) after 3 weeks of intervention as compared to the baseline (P = 0.03). GAA intervention positively affected both plasma GAA and creatine (P < 0.05), while no effects of intervention were reported for plasma glutamine. Results indicate that supplemental GAA affects peripheral GABA metabolism, and potentially down-regulates GABA synthesis in peripheral tissues. Possible GABAergic action of dietary GAA adds to the safety profile of this novel dietary supplement.

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

Sex specific differences in hepatic and plasma lipid profiles in healthy cats pre and post spaying and neutering: relationship with feline hepatic lipidosis.

PubMed

Valtolina, Chiara; Vaandrager, Arie B; Favier, Robert P; Tuohetahuntila, Maidina; Kummeling, Anne; Jeusette, Isabelle; Rothuizen, Jan; Robben, Joris H

2017-08-08

A link between lipid metabolism and disease has been recognized in cats. Since hepatic lipidosis is a frequent disorder in cats, the aim of the current study was to evaluate liver and plasma lipid dimorphism in healthy cats and the effects of gonadectomy on lipid profiling. From six female and six male cats plasma and liver lipid profiles before and after spaying/neutering were assessed and compared to five cats (three neutered male and two spayed female) diagnosed with hepatic lipidosis. Intact female cats had a significantly lower level of plasma triacylglycerides (TAG) and a higher liver level of the long chain polyunsaturated fatty acid arachidonic acid (AA) compared to their neutered state. Both male and female cats with lipidosis had a higher liver, but not plasma TAG level and an increased level of plasma and liver sphingomyelin compared to the healthy cats. Although lipid dimorphism in healthy cats resembles that of other species, intact female cats show differences in metabolic configuration that could predispose them to develop hepatic lipidosis. The increased sphingomyelin levels in cats with lipidosis could suggest a potential role in the pathogenesis of hepatic lipidosis in cats.

Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease.

PubMed

Yilmaz, Hale; Sahin, Sinan; Sayar, Nurten; Tangurek, Burak; Yilmaz, Mehmet; Nurkalem, Zekeriya; Onturk, Ebru; Cakmak, Nazmiye; Bolca, Osman

2007-12-01

Hyperhomocysteinaemia is related with premature coronary artery disease and adverse cardiac events in patients with coronary artery disease (CAD). It is assumed that hyper-homocysteinaemia causes endothelial dysfunction. In this study, the effect of folic acid and oral N-acetylcysteine (NAC) therapies on plasma homocysteine levels and endothelial function were evaluated in hyperhomocysteinaemic patients with CAD. 60 patients were randomized to either folic acid 5 mg or NAC 600 mg or placebo daily for eight weeks. Brachial artery endothelial functions were studied by using high-resolution ultrasound and assessed by measuring endothelium-dependent dilation (EDD) and endothelium-independent dilation (NEDD). Folic acid and NAC therapies decreased plasma homocysteine (from 21.7 +/- 8.7 micromol/l to 12.5 +/- 2.5 micromol/l, P < 0.001; from 20.9 +/- 7.6 micromol/l to 15.6 +/- 4.3 micromol/l, P = 0.03, respectively), and increased EDD (6.7 +/- 6.1% P = 0.002, 4.4 +/- 2.6% P < 0.001, respectively) compared with placebo. There was no significant difference in improving EDD between the folic acid and the NAC group (6.7 +/- 6.1%, 4.4 +/- 2.6%, P = 0. 168). In the univariate analyses there was an inverse correlation between the post-treatment homocysteine level and the percent change in EDD with folic acid therapy (r= -0.490, P = 0.028), but there was no correlation with the NAC therapy (r = 0.259, P = 0.333) In patients with hyperhomocysteinaemic CAD, folic acid and NAC lowered plasma homocysteine levels and improved endothelial function. The effects of both treatments in improvement of EDD were similar.

Associations between five-factor model of the Positive and Negative Syndrome Scale and plasma levels of monoamine metabolite in patients with schizophrenia.

PubMed

Watanabe, Kenya; Miura, Itaru; Kanno-Nozaki, Keiko; Horikoshi, Sho; Mashiko, Hirobumi; Niwa, Shin-Ichi; Yabe, Hirooki

2015-12-15

The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese-American Adults: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Diep, Cassandra S; Lemaitre, Rozenn N; Chen, Tzu-An; Baranowski, Tom; Lutsey, Pamela L; Manichaikul, Ani W; Rich, Stephen S; St-Jules, David E; Steffen, Brian T; Tsai, Michael Y; Siscovick, David S; Frazier-Wood, Alexis C

2016-01-01

Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults. Participants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated) to 5 (most acculturated) points. α-Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake. Absence of associations between acculturation and plasma phospholipid fatty acids suggests that changes in the plasma phospholipid fatty acids studied do not account for the observed associations of acculturation to the U.S. and cardiovascular disease risk. Similar findings were observed for eicosapentaenoic acid and docosahexaenoic acid, when using dietary intake. However, the observed associations between dietary n-6 fatty acids and acculturation in Hispanic individuals suggest that dietary intake may be more informative than phospholipids when investigating acculturation effects. In Chinese individuals, acculturation may have a possible protective effect through decreased arachidonic acid intake. Further research on dietary fatty acids and other cardiovascular disease biomarkers is needed to identify possible etiologic mechanisms between acculturation and cardiovascular disease.

Effects of Souvenaid on plasma micronutrient levels and fatty acid profiles in mild and mild-to-moderate Alzheimer's disease.

PubMed

Rijpma, Anne; Meulenbroek, Olga; van Hees, Anneke M J; Sijben, John W C; Vellas, Bruno; Shah, Raj C; Bennett, David A; Scheltens, Philip; Olde Rikkert, Marcel G M

2015-01-01

Circulating levels of uridine, selenium, vitamins B12, E and C, folate, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been shown to be lower in patients with Alzheimer's disease (AD) than in healthy individuals. These low levels may affect disease pathways involved in synapse formation and neural functioning. Here, we investigated whether, and to what extent, circulating levels of micronutrients and fatty acids can be affected by oral supplementation with Souvenaid (containing a specific nutrient combination), using data derived from three randomized clinical trials (RCT) and an open-label extension (OLE) study with follow-up data from 12 to 48 weeks. Subjects with mild (RCT1, RCT2) or mild-to-moderate AD (RCT3) received active or control product once daily for 12-24 weeks or active product during the 24-week OLE following RCT2 (n = 212-527). Measurements included plasma levels of B vitamins, choline, vitamin E, selenium, uridine and homocysteine and proportions of DHA, EPA and total n-3 long-chain polyunsaturated fatty acids in plasma and erythrocytes. Between-group comparisons were made using t tests or non-parametric alternatives. We found that 12-24-week active product intake increased plasma and/or erythrocyte micronutrients: uridine; choline; selenium; folate; vitamins B6, B12 and E; and fatty acid levels of DHA and EPA (all p < 0.001). In the OLE study, similar levels were reached in former control product/initial active product users, whereas 24-week continued active product intake showed no suggestion of a further increase in nutrient levels. These data show that circulating levels of nutrients known to be decreased in the AD population can be increased in patients with mild and mild-tomoderate AD by 24-48-week oral supplementation with Souvenaid. In addition, to our knowledge, this is the first report of the effects of sustained dietary intake of uridine monophosphate on plasma uridine levels in humans. Uptake of nutrients is observed within 6 weeks, and a plateau phase is reached for most nutrients during prolonged intake, thus increasing the availability of precursors and cofactors in the circulation that may be used for the formation and function of neuronal membranes and synapses in the brain.

New approaches to evaluate sympathoadrenal system activity in experiments on Earth and in space

NASA Astrophysics Data System (ADS)

Kvetnansky, R.; Noskov, V. B.; Blazicek, P.; Macho, L.; Grigoriev, A. I.; Goldstein, D. S.; Kopin, I. J.

In previous studies the activity of the sympathoadrenal system (SAS) in cosmonauts during space flights was evaluated by measuring plasma catecholamines (CA) levels and urinary CA and their metabolites concentrations. Plasma CA levels are accepted indicators of SAS activity, however, they are determined by the plasma clearances as well as the rates of CA release (spillover-SO) into the bloodstream. Nowadays methods are available which evaluate not only plasma levels of CA but also their release, spillover, uptake, reuptake, degradation and also CA synthesis in vivo measured by plasma levels of dihydroxyphenylalanine (DOPA). Plasma concentrations of DOPA, the CA noradrenaline (NE), adrenaline (ADR), and dopamine (DA), the deaminated catechol metabolites dihydroxyphenylglycol (DHPG) and dihydroxyphenylacetic acid (DOPAC), and the O-methylated metabolites methoxyhydroxyphenylglycol (MHPG) and homovanillic acid (HVA) were measured during immobilization stress (IMO) in conscious rats. Radiotracer methods were used to measure NE SO. IMO markedly increased arterial NE levels but NE SO was less elevated bacause the NE clearance was slightly reduced in IMO rats. Simultaneous measurements of plasma CA and their metabolites provide another means to obtain information about SAS function. For instance, dissociation between changes of plasma DHPG and NE levels can indicate changes in neuronal reuptake of NE. We found marked parallel increases in plasma NE and DHPG levels during acute IMO; however after repeated IMO, plasma NE levels were increased but DHPG responses were less pronounced suggesting a reduced NE reuptake. DOPA, the CA precursor, circulates in plasma at a concentration higher than NE. During stress, increased sympathoneural outflow stimulates DOPA synthesis and release into the circulation supporting the view that changes in plasma DOPA levels during stress reflect in vivo changes in the rate of CA synthesis. We propose to measure the new plasma indicators of SAS activity in cosmonauts and/or in animals before, during and after space flights.

Lipid peroxide, alpha-tocopherol and retinoid levels in plasma and liver of rats fed diets containing beta-carotene and 13-cis-retinoic acid.

PubMed

Alam, S Q; Alam, B S

1983-12-01

The effect of feeding large amounts of beta-carotene and 13-cis-retinoic acid (RA) on plasma and liver levels of alpha-tocopherol, lipid peroxides and retinoids was studied. Groups of young male rats were fed semipurified diets supplemented with 0, 100 mg/kg beta-carotene, 20 and 100 mg/kg 13-cis-RA. After feeding the various diets for 11 weeks, rats were killed and the concentrations of lipid peroxides, alpha-tocopherol, and retinoids were measured in blood plasma and liver. Peroxide levels were increased and alpha-tocopherol levels were decreased in plasma as well as liver of rats fed diets containing 13-cis-RA; this effect seems to be dose dependent, beta-Carotene had no significant effect on either of the above parameters. There was a decrease in the liver and plasma concentrations of retinol in rats fed 13-cis-RA; the levels of RA were generally higher in these two groups. The results suggest that the mechanism whereby 13-cis-RA increases the tissue peroxide levels may be related to its ability to decrease alpha-tocopherol levels.

The impact of Roux-en-Y gastric bypass surgery on normal metabolism in a porcine model

PubMed Central

Lindqvist, Andreas; Ekelund, Mikael; Garcia-Vaz, Eliana; Ståhlman, Marcus; Pierzynowski, Stefan; Gomez, Maria F.; Rehfeld, Jens F.; Groop, Leif; Hedenbro, Jan

2017-01-01

Background A growing body of literature on Roux-en-Y gastric bypass surgery (RYGB) has generated inconclusive results on the mechanism underlying the beneficial effects on weight loss and glycaemia, partially due to the problems of designing clinical studies with the appropriate controls. Moreover, RYGB is only performed in obese individuals, in whom metabolism is perturbed and not completely understood. Methods In an attempt to isolate the effects of RYGB and its effects on normal metabolism, we investigated the effect of RYGB in lean pigs, using sham-operated pair-fed pigs as controls. Two weeks post-surgery, pigs were subjected to an intravenous glucose tolerance test (IVGTT) and circulating metabolites, hormones and lipids measured. Bile acid composition was profiled after extraction from blood, faeces and the gallbladder. Results A similar weight development in both groups of pigs validated our experimental model. Despite similar changes in fasting insulin, RYGB-pigs had lower fasting glucose levels. During an IVGTT RYGB-pigs had higher insulin and lower glucose levels. VLDL and IDL were lower in RYGB- than in sham-pigs. RYGB-pigs had increased levels of most amino acids, including branched-chain amino acids, but these were more efficiently suppressed by glucose. Levels of bile acids in the gallbladder were higher, whereas plasma and faecal bile acid levels were lower in RYGB- than in sham-pigs. Conclusion In a lean model RYGB caused lower plasma lipid and bile acid levels, which were compensated for by increased plasma amino acids, suggesting a switch from lipid to protein metabolism during fasting in the immediate postoperative period. PMID:28257455

Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS).

PubMed

Kim, Ji Young; Park, Ju Yeon; Kim, Oh Yoen; Ham, Bo Mi; Kim, Hyun-Jin; Kwon, Dae Young; Jang, Yangsoo; Lee, Jong Ho

2010-09-03

Obesity is currently epidemic in many countries worldwide and is strongly related to diabetes and cardiovascular disease. This study investigated the differences in metabolomic profiling between overweight/obese and normal-weight men. Overweight/obese (n=30) and age-matched, normal-weight men (n=30) were included. Anthropometric parameters, conventional metabolites, and biomarkers were measured. Metabolomic profiling was analyzed with UPLC-Q-TOF MS. Overweight/obese men showed higher levels of HOMA-IR, triglycerides, total cholesterol, and LDL-cholesterol, and lower levels of HDL-cholesterol and adiponectin than lean men. Overweight/obese men showed higher proportion of stearic acid and lower proportion of oleic acid in serum phospholipids. Additionally, overweight/obese individuals showed higher fat intake and lower ratio of polyunsaturated fatty acids to saturated fatty acids. We identified three lyso-phosphatidylcholine (lysoPC) as potential plasma markers and confirmed eight known metabolites for overweight/obesity men. Especially, overweight/obese subjects showed higher levels of lysoPC C14:0 and lysoPC C18:0 and lower levels of lysoPC C18:1 than lean subjects. Results confirmed abnormal metabolism of two branched-chain amino acids, two aromatic amino acids, and fatty acid synthesis and oxidation in overweight/obese men. Additionally, the amount of dietary saturated fat may influence the proportion of saturated fatty acids in serum phospholipids and the degree of saturation of the constituent acyl group of plasma lysoPC.

Comparison of the effects of nicotinic acid and nicotinamide degradation on plasma betaine and choline levels.

PubMed

Sun, Wu-Ping; Zhai, Ming-Zhu; Li, Da; Zhou, Yiming; Chen, Na-Na; Guo, Ming; Zhou, Shi-Sheng

2017-08-01

The present study was to compare the effects of nicotinic acid and nicotinamide on the plasma methyl donors, choline and betaine. Thirty adult subjects were randomly divided into three groups of equal size, and orally received purified water (C group), nicotinic acid (300 mg, NA group) or nicotinamide (300 mg, NM group). Plasma nicotinamide, N 1 -methylnicotinamide, homocysteine, betaine and choline levels before and 1.5-h and 3-h post-dosing, plasma normetanephrine and metanephrine concentrations at 3-h post-dosing, and the urinary excretion of N 1 -methyl-2-pyridone-5-carboxamide during the test period were examined. The level of 3-h plasma nicotinamide, N 1 -methylnicotinamide, homocysteine, the urinary excretion of N 1 -methyl-2-pyridone-5-carboxamide and pulse pressure (PP) in the NM group was 221%, 3972%, 61%, 1728% and 21.2% higher than that of the control group (P < 0.01, except homocysteine and PP P < 0.05), while the 3-h plasma betaine, normetanephrine and metanephrine level in the NM group was 24.4%, 9.4% and 11.7% lower (P < 0.05, except betaine P < 0.01), without significant difference in choline levels. Similar but less pronounced changes were observed in the NA group, with a lower level of 3-h plasma N 1 -methylnicotinamide (1.90 ± 0.20 μmol/l vs. 3.62 ± 0.27 μmol/l, P < 0.01) and homocysteine (12.85 ± 1.39 μmol/l vs. 18.08 ± 1.02 μmol/l, P < 0.05) but a higher level of betaine (27.44 ± 0.71 μmol/l vs. 23.52 ± 0.61 μmol/l, P < 0.05) than that of the NM group. The degradation of nicotinamide consumes more betaine than that of nicotinic acid at identical doses. This difference should be taken into consideration in niacin fortification. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Plasma Homocysteine, Serum Folic Acid, Serum Vitamin B12, Serum Vitamin B6, MTHFR, and Risk of Normal-Tension Glaucoma.

PubMed

Li, Jinmiao; Xu, Fan; Zeng, Rui; Gong, Haijun; Lan, Yuqing

2016-02-01

This meta-analysis aims to comprehensively evaluate the association between total homocysteine (tHcy) levels, serum folic acid, vitamin B12, vitamin B6 levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype, and risk of normal-tension glaucoma (NTG). A systematic search of the EMBASE and PubMed databases was performed to evaluate plasma tHcy levels, serum folic acid, B vitamins' mean difference, and odds ratios of MTHFR C677T genotype between cases and controls. A total of 7 studies including 458 cases and 555 controls meeting the inclusion criteria were involved in this meta-analysis. There were 4 studies for tHcy (149 cases and 148 controls), 2 studies for vitamin B6, vitamin B12, and folate (90 cases and 82 controls), and 4 studies for MTHFR (343 cases and 449 controls). Overall, the mean plasma tHcy levels, serum folic acids, vitamin B12, and vitamin B6 levels were 1.16 μmol/L [95% confidence interval (CI), -0.13, 2.45], -0.62 μmol/L (95% CI, -1.98, 0.74), 5.81 μmol/L (95% CI, -3.53, 15.14), and -16.79 μmol/L (95% CI, -86.09, 52.51). MTHFR TT genotype was found to be unrelated to NTG risk (odds ratio=1.08; 95% CI, 0.69, 1.69). NTG is not associated with elevated plasma tHcy, serum folic acid, serum vitamin B12, serum vitamin B6, and MTHFR C677T genotype.

Dietary flavonoids increase plasma very long-chain (n-3) fatty acids in rats.

PubMed

Toufektsian, Marie-Claire; Salen, Patricia; Laporte, François; Tonelli, Chiara; de Lorgeril, Michel

2011-01-01

Flavonoids probably contribute to the health benefits associated with the consumption of fruit and vegetables. However, the mechanisms by which they exert their effects are not fully elucidated. PUFA of the (n-3) series also have health benefits. Epidemiological and clinical studies have suggested that wine flavonoids may interact with the metabolism of (n-3) PUFA and increase their blood and cell levels. The present studies in rats were designed to assess whether flavonoids actually increase plasma levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the main very long-chain (n-3) PUFA. Rats were fed a corn-derived anthocyanin (ACN)-rich (ACN-rich) or ACN-free diet with constant intakes of plant and marine (n-3) PUFA for 8 wk (Expt. 1). Plasma fatty acids were measured by GC. The ACN-rich diet contained ~0.24 ± 0.01 mg of ACN/g pellets. There were no significant differences between groups in the main saturated, monounsaturated, and (n-6) fatty acids. In contrast, plasma EPA and DHA were greater in the ACN-rich diet group than in the ACN-free diet group (P < 0.05). We obtained similar results in 2 subsequent experiments in which rats were administered palm oil (80 μL/d) and consumed the ACN-rich or ACN-free diet (Expt. 2) or were supplemented with fish oil (60 mg/d, providing 35 mg DHA and 12 mg EPA) and consumed the ACN-rich or ACN-free diet (Expt. 3). In both experiments, plasma EPA and DHA were significantly greater in the ACN-rich diet group. These studies demonstrate that the consumption of flavonoids increases plasma very long-chain (n-3) PUFA levels. These data confirm previous clinical and epidemiological studies and provide new insights into the health benefits of flavonoids.

Calcium is a key constituent for maintaining the in vitro properties of platelets suspended in the bicarbonate-containing additive solution M-sol with low plasma levels.

PubMed

Wagner, Stephen J; Skripchenko, Andrey; Myrup, Andrew; Thompson-Montgomery, Dedeene; Awatefe, Helen; Moroff, Gary

2010-05-01

Commercially available additive solutions (ASs) require 30% to 35% plasma for optimal storage of platelets (PLTs). PLTs suspended in M-sol, a bicarbonate-based experimental platelet additive solution (PAS), maintain in vitro PLT properties during storage with low levels of plasma (< or =5%). Four different formulations of M-sol were prepared at the optimal pH (6.1): M-sol, M-sol without calcium, M-sol without citric acid, and M-sol without calcium and citric acid. Apheresis PLT units (100% plasma) were equally divided into five 50-mL aliquots in PL732 containers, centrifuged, and resuspended to prepare units suspended in the four different PASs (95%) with 5% plasma and 1 unit in 100% plasma. Units (n = 10) were stored under standard conditions and assayed for in vitro properties on Days 1, 5, and 7. The data were analyzed by analysis of variance for repeated measures (n = 10, p < 0.001). On Day 5 of storage, PLTs suspended in the M-sol formulation containing calcium but lacking citric acid had similar pH, extent of shape change (ESC) values, and percentage of CD62-positive PLTs and greater hypotonic shock response (HSR) and percentage of discoid PLTs compared to those of PLTs suspended in 100% plasma. In contrast, PLTs suspended in the M-sol formulation lacking calcium had lesser ESC values, greater percentage of CD62-positive PLTs, and similar HSR values and percentage of discoid PLTs compared to those of PLTs suspended in 100% plasma on Day 5 (p < 0.001). Calcium plays an important role in maintaining CD62-negative PLTs and relatively high ESC in 5% plasma. The removal of citric acid from M-sol may improve PLT storage properties with low plasma levels.

Response of plasma membrane H+-ATPase in rice (Oryza sativa) seedlings to simulated acid rain.

PubMed

Liang, Chanjuan; Ge, Yuqing; Su, Lei; Bu, Jinjin

2015-01-01

Understanding the adaptation of plants to acid rain is important to find feasible approaches to alleviate such damage to plants. We studied effects of acid rain on plasma membrane H(+)-ATPase activity and transcription, intracellular H(+), membrane permeability, photosynthetic efficiency, and relative growth rate during stress and recovery periods. Simulated acid rain at pH 5.5 did not affect plasma membrane H(+)-ATPase activity, intracellular H(+), membrane permeability, photosynthetic efficiency, and relative growth rate. Plasma membrane H(+)-ATPase activity and transcription in leaves treated with acid rain at pH 3.5 was increased to maintain ion homeostasis by transporting excessive H(+) out of cells. Then intracellular H(+) was close to the control after a 5-day recovery, alleviating damage on membrane and sustaining photosynthetic efficiency and growth. Simulated acid rain at pH 2.5 inhibited plasma membrane H(+)-ATPase activity by decreasing the expression of H(+)-ATPase at transcription level, resulting in membrane damage and abnormal intracellular H(+), and reduction in photosynthetic efficiency and relative growth rate. After a 5-day recovery, all parameters in leaves treated with pH 2.5 acid rain show alleviated damage, implying that the increased plasma membrane H(+)-ATPase activity and its high expression were involved in repairing process in acid rain-stressed plants. Our study suggests that plasma membrane H(+)-ATPase can play a role in adaptation to acid rain for rice seedlings.

The effect of amino acid infusion on anesthesia-induced hypothermia in muscle atrophy model rats.

PubMed

Kanazawa, Masahiro; Ando, Satoko; Tsuda, Michio; Suzuki, Toshiyasu

2010-01-01

An infusion of amino acids stimulates heat production in skeletal muscle and then attenuates the anesthesia-induced hypothermia. However, in a clinical setting, some patients have atrophic skeletal muscle caused by various factors. The present study was therefore conducted to investigate the effect of amino acids on the anesthesia-induced hypothermia in the state of muscle atrophy. As the muscle atrophy model, Sprague-Dawley rats were subjected to hindlimb immobilization for 2 wk. Normal rats and atrophy model rats were randomly assigned to one of the two treatment groups: saline or amino acids (n=8 for each group). Test solutions were administered intravenously to the rats under sevoflurane anesthesia for 180 min, and the rectal temperature was measured. Plasma samples were collected for measurement of insulin, blood glucose, and free amino acids. The rectal temperature was significantly higher in the normal-amino acid group than in the muscle atrophy-amino acid group from 75 to 180 min. The plasma insulin level was significantly higher in the rats given amino acids than in the rats given saline in both normal and model groups. In the rats given amino acids, plasma total free amino acid concentration was higher in the model group than in the normal group. These results indicate that skeletal muscle plays an important role in changes in body temperature during anesthesia and the effect of amino acids on anesthesia-induced hypothermia decreases in the muscle atrophy state. In addition, intravenous amino acids administration during anesthesia induces an increase in the plasma insulin level.

Plasma n-6 Fatty Acid Levels Are Associated With CD4 Cell Counts, Hospitalization, and Mortality in HIV-Infected Patients.

PubMed

Kabagambe, Edmond K; Ezeamama, Amara E; Guwatudde, David; Campos, Hannia; Fawzi, Wafaie

2016-12-15

Fatty acids, including n-6 series, modulate immune function, but their effect on CD4 cell counts, death, or hospitalization in HIV-infected patients on antiretroviral therapy is unknown. In a randomized trial for effects of multivitamins in HIV-infected patients in Uganda, we used gas chromatography to measure plasma n-6 fatty acids at baseline; determined CD4 counts at baseline, 3, 6, 12, and 18 months; and recorded hospitalization or death events. The associations of fatty acids with CD4 counts and events were analyzed using repeated-measures analysis of variance and Cox regression, respectively. Among 297 patients with fatty acids measurements, 16 patients died and 69 were hospitalized within 18 months. Except for linoleic acid, n-6 fatty acids levels were positively associated with CD4 counts at baseline but not during follow-up. In models that included all 5 major n-6 fatty acids, age; sex; body mass index; anemia status; use of antiretroviral therapy, multivitamin supplements, and alcohol; and the risk of death or hospitalization decreased significantly with an increase in linoleic acid and gamma-linolenic acid levels, whereas associations for dihomo-gamma-linolenic acid, arachidonic acid, and aolrenic acid were null. The hazard ratios (95% confidence intervals) per 1 SD increase in linoleic acid and gamma-linolenic acid were 0.73 (0.56-0.94) and 0.51 (0.36-0.72), respectively. Gamma-linolenic acid remained significant (hazard ratio = 0.51; 95% confidence interval: 0.35 to 0.68) after further adjustment for other plasma fatty acids. Lower levels of gamma-linolenic acid are associated with lower CD4 counts and an increased risk of death or hospitalization. These results suggest a potential for using n-6 fatty acids to improve outcomes from antiretroviral therapy.

Normal Postprandial Nonesterified Fatty Acid Uptake in Muscles Despite Increased Circulating Fatty Acids in Type 2 Diabetes

PubMed Central

Labbé, Sébastien M.; Croteau, Etienne; Grenier-Larouche, Thomas; Frisch, Frédérique; Ouellet, René; Langlois, Réjean; Guérin, Brigitte; Turcotte, Eric E.; Carpentier, André C.

2011-01-01

OBJECTIVE Postprandial plasma nonesterified fatty acid (NEFA) appearance is increased in type 2 diabetes. Our objective was to determine whether skeletal muscle uptake of plasma NEFA is abnormal during the postprandial state in type 2 diabetes. RESEARCH DESIGN AND METHODS Thigh muscle blood flow and oxidative metabolism indexes and NEFA uptake were determined using positron emission tomography coupled with computed tomography (PET/CT) with [11C]acetate and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (18FTHA) in seven healthy control subjects (CON) and seven subjects with type 2 diabetes during continuous oral intake of a liquid meal to achieve steady postprandial NEFA levels with insulin infusion to maintain similar plasma glucose levels in both groups. RESULTS In the postprandial state, plasma NEFA level was higher in type 2 diabetic subjects versus CON (P < 0.01), whereas plasma glucose was at the same level in both groups. Muscle NEFA fractional extraction and blood flow index levels were 56% (P < 0.05) and 24% (P = 0.27) lower in type 2 diabetes, respectively. However, muscle NEFA uptake was similar to that of CON (quadriceps femoris [QF] 1.47 ± 0.23 vs. 1.37 ± 0.24 nmol ⋅ g−1 ⋅ min−1, P = 0.77; biceps femoris [BF] 1.54 ± 0.26 vs. 1.46 ± 0.28 nmol ⋅ g−1 ⋅ min−1, P = 0.85). Muscle oxidative metabolism was similar in both groups. Muscle NEFA fractional extraction and blood flow index were strongly and positively correlated (r = 0.79, P < 0.005). CONCLUSIONS Postprandial muscle NEFA uptake is normal despite elevated systemic NEFA levels and acute normalization of plasma glucose in type 2 diabetes. Lower postprandial muscle blood flow with resulting reduction in muscle NEFA fractional extraction may explain this phenomenon. PMID:21228312

Effect of a plant sterol, fish oil and B vitamin combination on cardiovascular risk factors in hypercholesterolemic children and adolescents: a pilot study

PubMed Central

2013-01-01

Background Assessment of cardiovascular disease (CVD) risk factors can predict clinical manifestations of atherosclerosis in adulthood. In this pilot study with hypercholesterolemic children and adolescents, we investigated the effects of a combination of plant sterols, fish oil and B vitamins on the levels of four independent risk factors for CVD; LDL-cholesterol, triacylglycerols, C-reactive protein and homocysteine. Methods Twenty five participants (mean age 16 y, BMI 23 kg/m2) received daily for a period of 16 weeks an emulsified preparation comprising plant sterols esters (1300 mg), fish oil (providing 1000 mg eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)) and vitamins B12 (50 μg), B6 (2.5 mg), folic acid (800 μg) and coenzyme Q10 (3 mg). Atherogenic and inflammatory risk factors, plasma lipophilic vitamins, provitamins and fatty acids were measured at baseline, week 8 and 16. Results The serum total cholesterol, LDL- cholesterol, VLDL-cholesterol, subfractions LDL-2, IDL-1, IDL-2 and plasma homocysteine levels were significantly reduced at the end of the intervention period (p<0.05). The triacylglycerols levels decreased by 17.6%, but did not reach significance. No significant changes in high sensitivity C-reactive protein, HDL-cholesterol and apolipoprotein A-1 were observed during the study period. After standardisation for LDL cholesterol, there were no significant changes in the levels of plasma γ-tocopherol, β-carotene and retinol, except for reduction in α-tocopherol levels. The plasma levels of n-3 fatty acids increased significantly with the dietary supplementation (p<0.05). Conclusions Daily intake of a combination of plant sterols, fish oil and B vitamins may modulate the lipid profile of hypercholesterolemic children and adolescents. Trial registration Current Controlled Trials ISRCTN89549017 PMID:23297818

Dietary (n-6 : n-3) Fatty Acids Alter Plasma and Tissue Fatty Acid Composition in Pregnant Sprague Dawley Rats

PubMed Central

Kassem, Amira Abdulbari; Abu Bakar, Md Zuki; Yong Meng, Goh; Mustapha, Noordin Mohamed

2012-01-01

The objective of this paper is to study the effects of varying dietary levels of n-6 : n-3 fatty acid ratio on plasma and tissue fatty acid composition in rat. The treatment groups included control rats fed chow diet only, rats fed 50% soybean oil (SBO): 50% cod liver oil (CLO) (1 : 1), 84% SBO: 16% CLO (6 : 1), 96% SBO: 4% CLO (30 : 1). Blood samples were taken at day 15 of pregnancy, and the plasma and tissue were analyzed for fatty acid profile. The n-3 PUFA in plasma of Diet 1 : 1 group was significantly higher than the other diet groups, while the total n-6 PUFA in plasma was significantly higher in Diet 30 : 1 group as compared to the control and Diet 1 : 1 groups. The Diet 1 : 1 group showed significantly greater percentages of total n-3 PUFA and docosahexaenoic acid in adipose and liver tissue, and this clearly reflected the contribution of n-3 fatty acids from CLO. The total n-6 PUFA, linoleic acid, and arachidonic acid were significantly difference in Diet 30 : 1 as compared to Diet 1 : 1 and control group. These results demonstrated that the dietary ratio of n-6 : n-3 fatty acid ratio significantly affected plasma and tissue fatty acids profile in pregnant rat. PMID:22489205

Characterisation of cold plasma treated beef and dairy lipids using spectroscopic and chromatographic methods.

PubMed

Sarangapani, Chaitanya; Ryan Keogh, David; Dunne, Julie; Bourke, Paula; Cullen, P J

2017-11-15

The efficacy of cold plasma for inactivation of food-borne pathogens in foods is established. However, insights on cold plasma-food interactions in terms of quality effects, particularly for oils and fats, are sparse. This study evaluated plasma-induced lipid oxidation of model matrices, namely dairy and meat fats. Product characterisation was performed using FTIR, 1 H NMR and chromatographic techniques. The oxidation of lipids by cold plasma followed the Criegee mechanism and typical oxidation products identified included ozonides, aldehydes (hexanal, pentenal, nonanal and nonenal) and carboxylic acids (9-oxononanoic acid, octanoic acid, nonanoic acid), along with hydroperoxides (9- and 13-hydroperoxy-octadecadienoylglycerol species). However, these oxidation products were only identified following extended treatment times of 30min and were also a function of applied voltage level. Understanding cold plasma interactions with food lipids and the critical parameters governing lipid oxidation is required prior to the industrial adoption of this technology for food products with high fat contents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of plasma and erythrocyte membrane fatty acid compositions in patients with end-stage renal disease and type 2 diabetes mellitus.

PubMed

Sertoglu, Erdim; Kurt, Ismail; Tapan, Serkan; Uyanik, Metin; Serdar, Muhittin A; Kayadibi, Huseyin; El-Fawaeir, Saad

2014-02-01

In this study, we aimed to compare the serum lipid profile and fatty acid (FA) compositions of erythrocyte membrane (EM) and plasma in three different patient groups (group 1: type 2 diabetes mellitus (T2DM)+end-stage renal disease (ESRD), group 2: ESRD, group 4: T2DM) and healthy controls (group 3) simultaneously. 40 ESRD patients treated with hemodialysis (HD) in Gulhane School of Medicine (20 with T2DM) and 32 controls (17 with T2DM, 15 healthy controls) were included in the study. Plasma and EM FA concentrations were measured by gas chromatography-flame ionization detector (GC-FID). Plasma and EM palmitic acid (PA) and stearic acid (SA) levels were significantly higher in T2DM patients compared to controls (p=0.040 and p=0.002 for plasma, p=0.001 and p=0.010 for EM, respectively). EM docosahexaenoic acid (DHA) levels were also significantly lower in patients with ESRD+T2DM and ESRD compared to controls (p=0.004 and p=0.037, respectively). Patients with insulin resistance display a pattern of high long chain saturated FAs (PA, SA and arachidic acids). However, while there are no recognized standards for normal EM DHA content, decreased levels of EM DHA in ESRD patient groups (groups 1 and 2) suggest that there may be reduced endogenous synthesis of DHA in HD subjects, due to the decreased functionality of desaturase and elongase enzymes. Because membrane PUFA content affects membrane fluidity and cell signaling, these findings are worthy of further investigation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Plasma appearance and correlation between coffee and green tea metabolites in human subjects.

PubMed

Renouf, Mathieu; Guy, Philippe; Marmet, Cynthia; Longet, Karin; Fraering, Anne-Lise; Moulin, Julie; Barron, Denis; Dionisi, Fabiola; Cavin, Christophe; Steiling, Heike; Williamson, Gary

2010-12-01

Coffee and green tea are two of the most widely consumed hot beverages in the world. Their respective bioavailability has been studied separately, but absorption of their respective bioactive phenolics has not been compared. In a randomised cross-over design, nine healthy subjects drank instant coffee and green tea. Blood samples were collected over 12 h and at 24 h to assess return to baseline. After green tea consumption, (-)-epigallocatechin (EGC) was the major catechin, appearing rapidly in the plasma; (-)-EGC gallate (EGCg) and (-)-epicatechin (EC) were also present, but (-)-EC gallate and C were not detected. Dihydroferulic acid and dihydrocaffeic acid were the major metabolites that appeared after coffee consumption with a long time needed to reach maximum plasma concentration, suggesting metabolism and absorption in the colon. Other phenolic acid equivalents (caffeic acid (CA), ferulic acid (FA) and isoferulic acid (iFA)) were detected earlier, and they peaked at lower concentrations. Summations of the plasma area under the curves (AUC) for the measured metabolites showed 1.7-fold more coffee-derived phenolic acids than green tea-derived catechins (P = 0.0014). Furthermore, we found a significant correlation between coffee metabolites based on AUC. Inter-individual differences were observed, but individuals with a high level of CA also showed a correspondingly high level of FA. However, no such correlation was observed between the tea catechins and coffee phenolic acids. Correlation between AUC and maximum plasma concentration was also significant for CA, FA and iFA and for EGCg. This implies that the mechanisms of absorption for these two classes of compounds are different, and that a high absorber of phenolic acids is not necessarily a high absorber of catechins.

Translating plasma and whole blood fatty acid compositional data into the sum of eicosapentaenoic and docosahexaenoic acid in erythrocytes.

PubMed

Stark, Ken D; Aristizabal Henao, Juan J; Metherel, Adam H; Pilote, Louise

2016-01-01

Specific blood levels of eicosapentaenoic plus docosahexaenoic acid (EPA+DHA, wt% of total) in erythrocytes or "the omega-3 index" have been recommended for cardio-protection, but fatty acids are often measured in different blood fractions. The ability to estimate the % of EPA+DHA in erythrocytes from the fatty acid composition of other blood fractions would enable clinical assessments of omega-3 status when erythrocyte fractions are not available and increase the ability to compare blood levels of omega-3 fatty acids across clinical studies. The fatty acid composition of baseline plasma, erythrocytes and whole blood samples from participants (n=1104) in a prospective, multicenter study examining acute coronary syndrome were determined. The ability to predict the % of EPA+DHA in erythrocytes from other blood fractions were examined using bivariate and multiple linear regression modelling. Concordance analysis was also used to compare the actual erythrocytes EPA+DHA values to values estimated from other blood fractions. EPA+DHA in erythrocytes was significantly (p<0.001) correlated EPA+DHA in plasma (r(2)=0.54) and whole blood (r(2)=0.79). Using multiple linear regression to predict EPA+DHA in erythrocytes resulted in stronger coefficients of determination in both plasma (R(2)=0.70) and whole blood (R(2)=0.84). Concordance analyses indicated agreement between actual and estimated EPA+DHA in erythrocytes, although estimating from plasma fatty acids appears to require translation by categorization rather than by translation as continuous data. This study shows that the fatty acid composition of different blood fractions can be used to estimate erythrocyte EPA+DHA in a population with acute coronary syndrome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Polymorphisms in genes involved in the triglyceride synthesis pathway and marine omega-3 polyunsaturated fatty acid supplementation modulate plasma triglyceride levels.

PubMed

Ouellette, Catherine; Cormier, Hubert; Rudkowska, Iwona; Guénard, Frédéric; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2013-01-01

Marine omega-3 (n-3) polyunsaturated fatty acids (PUFA) reduce plasma triglyceride (TG) levels. Genetic factors such as single nucleotide polymorphisms (SNPs) could be responsible for the variability of the plasma TG response to n-3 PUFA supplementation. Previous studies have demonstrated that n-3 PUFA supplementation using fish oil modified the expression levels of three genes involved in the TG synthesis pathway (GPAM, AGPAT3 and AGPAT4) in peripheral blood mononuclear cells. A total of 210 subjects consumed 5 g/day of a fish oil supplement for 6 weeks. Plasma lipids were measured before and after the supplementation period. Three SNPs in GPAM, 13 SNPs in AGPAT3 and 35 SNPs in AGPAT4 were genotyped. In an ANOVA for repeated measures adjusted for age, sex and BMI, genotype effects on plasma TG levels were observed for rs1838452 in AGPAT3 as well as for rs746731 and rs2293286 in AGPAT4. Genotype × supplementation interaction effects on plasma TG levels were observed for rs2792751 and rs17129561 in GPAM as well as for rs3798943 and rs9458172 in AGPAT4 (p < 0.05). These results suggest that SNPs in genes involved in the TG synthesis pathway may influence plasma TG levels after n-3 PUFA supplementation. © 2014 S. Karger AG, Basel.

Absorption and metabolism of bioactive molecules after oral consumption of cooked edible heads of Cynara scolymus L. (cultivar Violetto di Provenza) in human subjects: a pilot study.

PubMed

Azzini, E; Bugianesi, R; Romano, F; Di Venere, D; Miccadei, S; Durazzo, A; Foddai, M S; Catasta, G; Linsalata, V; Maiani, G

2007-05-01

The current growing interest for natural antioxidants has led to a renewed scientific attention for artichoke, due not only to its nutritional value, but, overall, to its polyphenolic content, showing strong antioxidant properties. The major constituents of artichoke extracts are hydroxycinnamic acids such as chlorogenic acid, dicaffeoylquinic acids caffeic acid and ferulic acid, and flavonoids such as luteolin and apigenin glycosides. In vitro studies, using cultured rat hepatocytes, have shown its hepatoprotective functions and in vivo studies have shown the inhibition of cholesterol biosynthesis in human subjects. Several studies have shown the effect on animal models of artichoke extracts, while information on human bioavailability and metabolism of hydroxycinnamates derivatives is still lacking. Results showed a plasma maximum concentration of 6.4 (SD 1.8) ng/ml for chlorogenic acid after 1 h and its disappearance within 2 h (P< 0.05). Peak plasma concentrations of 19.5 (SD 6.9) ng/ml for total caffeic acid were reached within 1 h, while ferulic acid plasma concentrations showed a biphasic profile with 6.4 (SD1.5) ng/ml and 8.4 (SD4.6) ng/ml within 1 h and after 8 h respectively. We observed a significant increase of dihydrocaffeic acid and dihydroferulic acid total levels after 8 h (P<0.05). No circulating plasma levels of luteolin and apigenin were present. Our study confirms the bioavailability of metabolites of hydroxycinnamic acids after ingestion of cooked edible Cynara scolymus L. (cultivar Violetto di Provenza).

Impacts of short-term acid and aluminum exposure on Atlantic salmon (Salmo salar) physiology: A direct comparison of parr and smolts

USGS Publications Warehouse

Monette, M.Y.; McCormick, S.D.

2008-01-01

Episodic acidification resulting in increased acidity and inorganic aluminum (Ali) is known to impact anadromous salmonids and has been identified as a possible cause of Atlantic salmon population decline. Sensitive life-stages such as smolts may be particularly vulnerable to impacts of short-term (days–week) acid/Al exposure, however the extent and mechanism(s) of this remain unknown. To determine if Atlantic salmon smolts are more sensitive than parr to short-term acid/Al, parr and smolts held in the same experimental tanks were exposed to control (pH 6.3–6.6, 11–37 μg l−1 Ali) and acid/Al (pH 5.0–5.4, 43–68 μg l−1 Ali) conditions in the lab, and impacts on ion regulation, stress response and gill Al accumulation were examined after 2 and 6 days. Parr and smolts were also held in cages for 2 and 6 days in a reference (Rock River, RR) and an acid/Al-impacted tributary (Ball Mountain Brook, BMB) of the West River in Southern Vermont. In the lab, losses in plasma Cl− levels occurred in both control parr and smolts as compared to fish sampled prior to the start of the study, however smolts exposed to acid/Al experienced additional losses in plasma Cl− levels (9–14 mM) after 2 and 6 days, and increases in plasma cortisol (4.3-fold) and glucose (2.9-fold) levels after 6 days, whereas these parameters were not significantly affected by acid/Al in parr. Gill Na+,K+-ATPase (NKA) activity was not affected by acid/Al in either life-stage. Both parr and smolts held at BMB (but not RR) exhibited declines in plasma Cl−, and increases in plasma cortisol and glucose levels; these differences were significantly greater in smolts after 2 days but similar in parr and smolts after 6 days. Gill NKA activity was reduced 45–54% in both life-stages held at BMB for 6 days compared to reference fish at RR. In both studies, exposure to acid/Al resulted in gill Al accumulation in parr and smolts, with parr exhibiting two-fold greater gill Al than smolts after 6 days. Our results indicate that smolts are more sensitive than parr to short-term acid/Al. Increased sensitivity of smolts appears to be independent of a reduction in gill NKA activity and greater gill Al accumulation. Instead, increased sensitivity of smolts is likely a result of both the acquisition of seawater tolerance while still in freshwater and heightened stress responsiveness in preparation for seawater entry and residence.

Determination of endogenous levels of 13-cis-retinoic acid (isotretinoin), all-trans-retinoic acid (tretinoin) and their 4-oxo metabolites in human and animal plasma by high-performance liquid chromatography with automated column switching and ultraviolet detection.

PubMed

Wyss, R; Bucheli, F

1997-10-24

A highly sensitive HPLC method with automated column switching was developed for the simultaneous determination of endogenous levels of 13-cis-retinoic acid (isotretinoin), all-trans-retinoic acid (tretinoin) and their 4-oxo metabolites in plasma samples from man, Cynomolgus monkey, rabbit, rat and mouse. Plasma (0.4 ml) was deproteinated by adding ethanol (1.5 ml) containing the internal standard acitretin. After centrifugation, 1.4 ml of the supernatant were directly injected onto the precolumn packed with LiChrospher 100 RP-18 (5 microm). 1.25% ammonium acetate and acetic acid-ethanol (8:2, v/v) was used as mobile phase during injection and 1% ammonium acetate and 2% acetic acid-ethanol (102:4, v/v) was added, on-line, to decrease the elution strength of the injection solution. After backflush purging of the precolumn, the retained components were transferred to the analytical column in the backflush mode, separated by gradient elution and detected at 360 nm. Two coupled Superspher 100 RP-18 endcapped columns (both 250x4 mm) were used for the separation, together with a mobile phase consisting of acetonitrile-water-10% ammonium acetate-acetic acid: (A) 600:300:60:10 (v/v/v/v), (B) 950:20:5:20 (v/v/v/v), and (C) 990:5:0:5 (v/v/v/v). The method was linear in the range 0.3-100 ng/ml, at least, with a quantification limit of 0.3 ng/ml. The mean recoveries from human plasma were 93.2%-94.4% and the mean inter-assay precision was 2.8%-3.2% (range 0.3-100 ng/ml). Similar results were obtained for animal plasma. The analytes were found to be stable in the plasma of all investigated species stored at -20 degrees C for 4.3 months and at -80 degrees C for 9 months, at least. At this temperature, human plasma samples were even stable for 2 years. The method was successfully applied to more than 6000 human and 1000 animal plasma samples from clinical and toxicokinetic studies. Endogenous levels determined in control patients and pregnant women were similar to published data from volunteers.

Comparative plasma salicylate and urine salicylurate levels following administration of aspirin, magnesium salicylate, and choline magnesium trisalicylate.

PubMed

Mason, W D

1980-11-01

Eighteen healthy volunteers were administered single doses of commercially available solid dosage forms of aspirin, magnesium salicylate (I), and choline magnesium trisalicylate (II), equivalent to approximately 500 mg of salicylic acid, in a randomized, complete crossover design. Plasma salicylate and urine salicylurate levels were measured by high-pressure liquid chromatography at frequent intervals following dosing; the resultant profiles, areas under the curve (AUC), and percentages of dose excreted as salicylurate were statistically analyzed by an analysis of variance. The plasma salicylate levels following the two dosage forms containing I and II were virtually identical when corrected for small differences in the dose. The plasma salicylic acid level following aspirin was approximately 10% lower during the 1.5--3.0-hr interval due to a portion of unhydrolyzed aspirin, but the dose-corrected AUC for the products tested did not differ significantly (p < 0.05). During the 24 hr following dosing, 66.5 +/- 12.1 68.4 +/- 7.1, and 60.9 +/- 14.1% of the salicylic acid were excreted as urine salicylurate for aspirin, I, and II, respectively, with no significant difference (p < 0.05). Based on this study, there are no significant differences in the rate and extent of absorption of salicylate following the three dosage forms tested, and the elimination kinetics of salicylic acid are not altered by these dosage forms.

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

PubMed

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

2002-08-01

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

Altered peripheral amino acid profile indicate a systemic impact of active celiac disease and a possible role of amino acids in disease pathogenesis.

PubMed

Torinsson Naluai, Åsa; Saadat Vafa, Ladan; Gudjonsdottir, Audur H; Arnell, Henrik; Browaldh, Lars; Nilsson, Staffan; Agardh, Daniel

2018-01-01

We have previously performed a Genome Wide Association and linkage study that indicated a new disease triggering mechanism involving amino acid metabolism and nutrient sensing signaling pathways. The aim of this study was to investigate if plasma amino acid levels differed among children with celiac disease compared with disease controls. Fasting plasma samples from 141 children with celiac disease and 129 non-celiac disease controls, were analyzed for amino acid levels by liquid chromatography-tandem mass spectrometry (LC/MS). A general linear model using age and experimental effects as covariates was used to compare amino acid levels between children with a diagnosis of celiac disease and controls. Seven out of twenty-three analyzed amino acids were elevated in children with celiac disease compared with controls (tryptophan, taurine, glutamic acid, proline, ornithine, alanine and methionine). The significance of the individual amino acids do not survive multiple correction, however, multivariate analyses of the amino acid profile showed significantly altered amino acid levels in children with celiac disease overall and after correction for age, sex and experimental effects (p = 8.4 × 10-8). These findings support the idea that amino acids could influence systemic inflammation and play a possible role in disease pathogenesis.

[Uric acid predicts type 2 diabetes mellitus in the general population].

PubMed

Cardona, Fernando; Rojo-Martínez, Gemma; de la Cruz Almaraz, María; Soriguer, Federico; García-Fuentes, Eduardo; Tinahones, Francisco José

2009-02-01

Abnormal uric acid levels are considered by some to be a risk factor for metabolic disorders, whereas others consider it to be just a marker. We therefore examined the association between plasma uric acid concentrations and the risk of type 2 diabetes mellitus. We undertook a prospective, 8-year study of 411 persons from the general population with no carbohydrate metabolism disorder at the start of the study evaluated by oral glucose overload. The following variables were measured at the beginning and end of the study: uric acid, triglycerides, cholesterol, high-density lipoprotein cholesterol, glucose and insulin in plasma, body mass index and waist-to-hip ratio. The participants were classified according to their plasma uric acid concentration, with a cut-off at the 33rd percentile (men, 291.45 and women, 208.18 micromol/l). Participants with plasma uric acid concentrations above the 33rd percentile at the start of the study had worse lipid and anthropometric profiles. These persons were at greater risk for carbohydrate disorder at the end of the 8- year follow-up study (relative risk, 1.73; 95% confidence interval, 1.04-2.8). No significant differences were found in age or in the remaining variables studied between these two groups. Increased uric acid levels in response to a possible chronic increase in oxidative stress may predict future disorders or complications such as type 2 diabetes in otherwise healthy persons.

Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

PubMed

Horas H Nababan, Saut; Nishiumi, Shin; Kawano, Yuki; Kobayashi, Takashi; Yoshida, Masaru; Azuma, Takeshi

2017-06-01

This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

Valine entry into rat brain after diet-induced changes in plasma amino acids

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

Tews, J.K.; Greenwood, J.; Pratt, O.E.

1987-01-01

Passage of amino acids across the blood-brain barrier is assumed to be modified by amino acid composition of the blood. To gain a better understanding of the effects of protein intake on brain amino acid uptake, the authors examined associations among diet, plasma amino acid patterns, and the rate of entry of valine into the brain. Rats were fed diets containing 6, 18, or 50% casein before receiving one meal of a diet containing 0, 6, 18, or 50% casein. After 4-7 h, they were anesthetized and infused intravenously with (/sup 14/C)valine for 5 min before plasma and brain samplesmore » were taken for determination of radioactivity and content of individual amino acids. As protein content of the meal was increased from 0 to 50% casein, plasma and brain concentrations of valine and most other large neutral amino acid (LNAA) increased severalfold; also the ratio of (/sup 14/C)valine in brain to that in plasma decreased by >50%, and the rate of valine entry into the brain increased 3.5-fold. The increase in valine flux slowed as plasma levels of LNAA, competitors for valine transport, increased. The results were far more dependent on protein content of the final meal than on that of the adaptation diet; thus changes in protein intake, as reflected in altered plasma amino acid patterns, markedly altered valine entry into the brain.« less

Salicylic acid plasma levels following multiple doses of Norgesic Forte and aspirin.

PubMed

Harrison, L I; Kehe, C R; Goldlust, M B; Kvam, D C; Bianchine, J R

1983-01-01

Plasma salicyclic acid levels from the recommended multiple dose regimen of Norgesic Forte (orphenadrine citrate, aspirin, and caffeine) were compared to those from an equivalent multiple dose regimen of aspirin alone in 24 volunteers. The drugs were administered double-blind so that side effects could also be compared. No statistically significant differences were found between Norgesic Forte and aspirin in peak or trough levels, time to peak level, area under the curve, or mean steady-state level of salicylic acid. Mean steady-state levels averaged 154 +/- 46 (+/- SD) and 152 +/- 49 micrograms/ml on days 5 and 10 following Norgesic Forte versus 161 +/- 49 and 154 +/- 47 micrograms/ml following aspirin. Thus, the aspirin in Norgesic Forte provides an anti-inflammatory amount of salicylic acid equivalent to that of plain aspirin. There was no evidence that the combination of orphenadrine citrate, caffeine, and aspirin in Norgesic Forte caused increased or unusual side effects compared with aspirin alone.

Plasma secretin, plasma cholecystokinin, pancreaticobiliary secretion, and fat absorption: effect of duodenal osmolality and polysorbate 80.

PubMed

Olsen, O; Schaffalitzky de Muckadell, O B; Cantor, P

1987-11-01

In 20 normal persons we investigated the effects of duodenal osmolality on the release of secretin and cholecystokinin (CCK), pancreaticobiliary secretion, and fat absorption after intestinal infusion of emulsified oleic acid (pH 6.0). The release of CCK was found to be unaffected by the changes in osmolality, whereas the plasma levels of secretin were affected in parallel with volume and bicarbonate secretion. An inverse relation was found between fatty acid absorption and release of secretin and bicarbonate secretion but not between fatty acid absorption and release of CCK. It is suggested that the secretin and CCK cells respond differently to emulsified oleic acid.

Insulin resistance and the metabolism of branched-chain amino acids in humans.

PubMed

Adeva, María M; Calviño, Jesús; Souto, Gema; Donapetry, Cristóbal

2012-07-01

Peripheral resistance to insulin action is the major mechanism causing the metabolic syndrome and eventually type 2 diabetes mellitus. The metabolic derangement associated with insulin resistance is extensive and not restricted to carbohydrates. The branched-chain amino acids (BCAAs) are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in conditions featuring insulin resistance, insulin deficiency, or both. Obesity, the metabolic syndrome and diabetes mellitus display a gradual increase in the plasma concentration of BCAAs, from the obesity-related low-grade insulin-resistant state to the severe deficiency of insulin action in diabetes ketoacidosis. Obesity-associated hyperinsulinemia succeeds in maintaining near-normal or slightly elevated plasma concentration of BCAAs, despite the insulin-resistant state. The low circulating levels of insulin and/or the deeper insulin resistance occurring in diabetes mellitus are associated with more marked elevation in the plasma concentration of BCAAs. In diabetes ketoacidosis, the increase in plasma BCAAs is striking, returning to normal when adequate metabolic control is achieved. The metabolism of BCAAs is also disturbed in other situations typically featuring insulin resistance, including kidney and liver dysfunction. However, notwithstanding the insulin-resistant state, the plasma level of BCAAs in these conditions is lower than in healthy subjects, suggesting that these organs are involved in maintaining BCAAs blood concentration. The pathogenesis of the decreased BCAAs plasma level in kidney and liver dysfunction is unclear, but a decreased afflux of these amino acids into the blood stream has been observed.

Association between polymorphisms in phospholipase A2 genes and the plasma triglyceride response to an n-3 PUFA supplementation: a clinical trial.

PubMed

Tremblay, Bénédicte L; Cormier, Hubert; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2015-02-21

Fish oil-derived long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), reduce plasma triglyceride (TG) levels. Genetic factors such as single-nucleotide polymorphisms (SNPs) found in genes involved in metabolic pathways of n-3 PUFA could be responsible for well-recognized heterogeneity in plasma TG response to n-3 PUFA supplementation. Previous studies have shown that genes in the glycerophospholipid metabolism such as phospholipase A2 (PLA2) group II, IV, and VI, demonstrate changes in their expression levels in peripheral blood mononuclear cells (PBMCs) after n-3 PUFA supplementation. A total of 208 subjects consumed 3 g/day of n-3 PUFA for 6 weeks. Plasma lipids were measured before and after the supplementation period. Five SNPs in PLA2G2A, six in PLA2G2C, eight in PLA2G2D, six in PLA2G2F, 22 in PLA2G4A, five in PLA2G6, and nine in PLA2G7 were genotyped. The MIXED Procedure for repeated measures adjusted for age, sex, BMI, and energy intake was used in order to test whether the genotype, supplementation or interaction (genotype by supplementation) were associated with plasma TG levels. The n-3 PUFA supplementation had an independent effect on plasma TG levels. Genotype effects on plasma TG levels were observed for rs2301475 in PLA2G2C, rs818571 in PLA2G2F, and rs1569480 in PLA2G4A. Genotype x supplementation interaction effects on plasma TG levels were observed for rs1805018 in PLA2G7 as well as for rs10752979, rs10737277, rs7540602, and rs3820185 in PLA2G4A. These results suggest that, SNPs in PLA2 genes may influence plasma TG levels during a supplementation with n-3 PUFA. This trial was registered at clinicaltrials.gov as NCT01343342.

Awake craniotomy induces fewer changes in the plasma amino acid profile than craniotomy under general anesthesia.

PubMed

Hol, Jaap W; Klimek, Markus; van der Heide-Mulder, Marieke; Stronks, Dirk; Vincent, Arnoud J; Klein, Jan; Zijlstra, Freek J; Fekkes, Durk

2009-04-01

In this prospective, observational, 2-armed study, we compared the plasma amino acid profiles of patients undergoing awake craniotomy to those undergoing craniotomy under general anesthesia. Both experimental groups were also compared with a healthy, age-matched and sex-matched reference group not undergoing surgery. It is our intention to investigate whether plasma amino acid levels provide information about physical and emotional stress, as well as pain during awake craniotomy versus craniotomy under general anesthesia. Both experimental groups received preoperative, perioperative, and postoperative dexamethasone. The plasma levels of 20 amino acids were determined preoperative, perioperative, and postoperatively in all groups and were correlated with subjective markers for pain, stress, and anxiety. In both craniotomy groups, preoperative levels of tryptophan and valine were significantly decreased whereas glutamate, alanine, and arginine were significantly increased relative to the reference group. Throughout time, tryptophan levels were significantly lower in the general anesthesia group versus the awake craniotomy group. The general anesthesia group had a significantly higher phenylalanine/tyrosine ratio, which may suggest higher oxidative stress, than the awake group throughout time. Between experimental groups, a significant increase in large neutral amino acids was found postoperatively in awake craniotomy patients, pain was also less and recovery was faster. A significant difference in mean hospitalization time was also found, with awake craniotomy patients leaving after 4.53+/-2.12 days and general anesthesia patients after 6.17+/-1.62 days; P=0.012. This study demonstrates that awake craniotomy is likely to be physically and emotionally less stressful than general anesthesia and that amino acid profiling holds promise for monitoring postoperative pain and recovery.

Plasma amino acid profiles are associated with insulin, C-peptide and adiponectin levels in type 2 diabetic patients

PubMed Central

Nakamura, H; Jinzu, H; Nagao, K; Noguchi, Y; Shimba, N; Miyano, H; Watanabe, T; Iseki, K

2014-01-01

Objectives: Plasma-free amino acid (PFAA) profiles have been associated with a future risk of developing diabetes or cardiovascular disease in nondiabetic subjects. These PFAA alterations might predominantly result from the metabolic shift caused by insulin resistance and visceral fat deposition. The variety of PFAA profiles within diabetic subjects is not well researched. In this study, we focused on type 2 diabetic subjects and examined the association between PFAA profiles and insulin- and glucose-related variables. Methods: Fifty-one Japanese subjects diagnosed with type 2 diabetes were recruited from an outpatient clinic. The plasma concentrations of 21 amino acids; glucose-related markers including glucose, hemoglobin A1c (HbA1c), glycoalbumin and 1,5-anhydroglucitol; insulin-related markers including insulin, C-peptide, and the homeostasis model assessment of insulin resistance; and adipocytokines including adiponectin and leptin were determined. The association of PFAA and other metabolic profiles were analyzed, and stratified analyses of the PFAAs and clinical characteristics were performed according to the fasting plasma insulin and HbA1c levels. In addition, the PFAA indices that correlate to visceral fat obesity were evaluated. Results: Although strong correlations between PFAAs and glucose-related markers were not observed, several amino acids (branched-chain amino acids, tryptophan, alanine, tyrosine, glutamate and proline) and PFAA indices that evaluate visceral obesity were highly correlated with insulin-related markers and adiponectin (P<0.001). In the group of diabetic patients with hyperinsulinemia, the amino acid levels were significantly increased, which generally demonstrated good concordance with insulin-related markers and adiponectin levels. Conclusions: The PFAA profiles in diabetic patients were strongly associated with hyperinsulinemia and hypoadiponectinemia, which might become risk evaluation factors for the development of cardiovascular diseases. PMID:25177913

Capillary electrophoresis tandem mass spectrometry determination of glutamic acid and homocysteine's metabolites: Potential biomarkers of amyotrophic lateral sclerosis.

PubMed

Cieslarova, Zuzana; Lopes, Fernando Silva; do Lago, Claudimir Lucio; França, Marcondes Cavalcante; Colnaghi Simionato, Ana Valéria

2017-08-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both lower and upper motor neurons, leading to muscle atrophy, paralysis, and death caused by respiratory failure or infectious complications. Altered levels of homocysteine, cysteine, methionine, and glutamic acid have been observed in plasma of ALS patients. In this context, a method for determination of these potential biomarkers in plasma by capillary electrophoresis tandem mass spectrometry (CE-MS/MS) is proposed herein. Sample preparation was carefully investigated, since sulfur-containing amino acids may interact with plasma proteins. Owing to the non-thiol sulfur atom in methionine, it was necessary to split sample preparation into two methods: i) determination of homocysteine and cysteine as S-acetyl amino acids; ii) determination of glutamic acid and methionine. All amino acids were separated within 25min by CE-MS/MS using 5molL -1 acetic acid as background electrolyte and 5mmolL -1 acetic acid in 50% methanol/H 2 O (v/v) as sheath liquid. The proposed CE-MS/MS method was validated, presenting RSD values below 6% and 11% for intra- and inter-day precision, respectively, for the middle concentration level within the linear range. The limits of detection ranged from 35 (homocysteine) to 268nmolL -1 (glutamic acid). The validated method was applied to the analysis of plasma samples from a group of healthy individuals and patients with ALS, showing the potential of glutamic acid and homocysteine metabolites as biomarkers of ALS. Copyright © 2017 Elsevier B.V. All rights reserved.

MicroRNA-134 plasma levels before and after treatment with valproic acid for epilepsy patients

PubMed Central

Wang, Xiaofeng; Luo, Yifeng; Liu, Shuangxi; Tan, Liming; Wang, Sanhu; Man, Rongyong

2017-01-01

Background Temporal lobe epilepsy is the second most common neurological disorders characterized by recurrent spontaneous seizures. MicroRNAs play a vital role in regulating synaptic plasticity, brain development and post-transcriptional expression of proteins. In both animal models of epilepsy and human patients, miR-134, a brain-specific microRNA has recently been identified as a potential regulator of epileptogenesis. Methods microRNA identified as targets for the actions of valproic acid (VPA) are known to have important effects in brain function. In this study, 59 new-onset epilepsy patients and 20 controls matched by sex and age were enrolled. Patients with a score < 3 were allocated into the mild group, 3-5 into the moderate group and >5 into the severe group. The plasma miRNA-134 level was quantitatively measured using real-time PCR. Results Plasma miRNA-134 level in new-onset epilepsy patients was significantly up-regulated when compared with that in healthy controls, and then considerably down-regulated after oral intake of valproic acid medication. The up-regulated plasma miRNA-134 levels may be directly associated with the pathophysiology and severity of epilepsy. Conclusion Plasma miRNA-134 in epilepsy may be considered as a potential peripheral biomarker that responds to the incidence of epilepsy and associates with use of anti-epilepsy drugs. PMID:29069823

Effect of a new injectable male contraceptive on the seminal plasma amino acids studied by proton NMR spectroscopy.

PubMed

Chaudhury, Koel; Sharma, Uma; Jagannathan, N R; Guha, Sujoy K

2002-09-01

Effect of RISUG, a newly developed male contraceptive, on various amino acids of seminal plasma ejaculates was studied by proton magnetic resonance spectroscopy at 400 MHz. Levels of amino acids were compared with the seminal plasma of obstructive azoospermia and controls. Glutamic acid, glutamine, and arginine were found to be high in concentration in human seminal plasma. The concentration of aromatic amino acids such as tyrosine, histidine, and phenylalanine in RISUG-injected subjects showed no significant difference compared to controls (p > 0.1); however, there was a statistically significant decrease in the concentration of these amino acids in obstructive azoospermia. The concentration of some prominent amino acids that showed overlapping resonances, such as isoleucine+leucine+valine (p < 0.01), alanine+isoleucine+lysine (p < 0.01), arginine+lysine+leucine (p < 0.01), and glutamic acid+glutamine (p < 0.01), showed a statistically significant decrease in RISUG-injected subjects compared to controls. Overlap of these amino acid resonances were noticed even at 600 MHz. In general, the total amino acids concentration in RISUG-injected subjects was found to be higher than in azoospermic subjects, confirming the occurrence of 'partial' obstructive azoospermia in subjects injected with this contraceptive.

Polymorphisms in genes involved in fatty acid β-oxidation interact with dietary fat intakes to modulate the plasma TG response to a fish oil supplementation.

PubMed

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2014-03-18

A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9-2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation.

Gene-nutrient interactions on the phosphoenolpyruvate carboxykinase influence insulin sensitivity in metabolic syndrome subjects.

PubMed

Perez-Martinez, Pablo; Garcia-Rios, Antonio; Delgado-Lista, Javier; Gjelstad, Ingrid M F; Gibney, James; Kieć-Wilk, Beata; Camargo, Antonio; Helal, Olfa; Karlström, Brita; Blaak, Ellen E; Hall, Wendy; Risérus, Ulf; Dembińska-Kieć, Aldona; Defoort, Catherine; Saris, Wim H M; Lovegrove, Julie A; Drevon, Christian A; Roche, Helen M; Lopez-Miranda, Jose

2013-08-01

Genetic background may interact with habitual dietary fat composition, and affect development of the metabolic syndrome (MetS). The phosphoenolpyruvate carboxykinase gene (PCK1) plays a significant role regulating glucose metabolism, and fatty acids are key metabolic regulators, which interact with transcription factors and influence glucose metabolism. We explored genetic variability at the PCK1 gene locus in relation to degree of insulin resistance and plasma fatty acid levels in MetS subjects. Moreover, we analyzed the PCK1 gene expression in the adipose tissue of a subgroup of MetS subjects according to the PCK1 genetic variants. Insulin sensitivity, insulin secretion, glucose effectiveness, plasma concentrations of C-peptide, fatty acid composition and three PCK1 tag-single nucleotide polymorphisms (SNPs) were determined in 443 MetS participants in the LIPGENE cohort. The rs2179706 SNP interacted with plasma concentration of n - 3 polyunsaturated fatty acids (n - 3 PUFA), which were significantly associated with plasma concentrations of fasting insulin, peptide C, and HOMA-IR. Among subjects with n - 3 PUFA levels above the population median, carriers of the C/C genotype exhibited lower plasma concentrations of fasting insulin (P = 0.036) and HOMA-IR (P = 0.019) as compared with C/C carriers with n - 3 PUFA below the median. Moreover, homozygous C/C subjects with n - 3 PUFA levels above the median showed lower plasma concentrations of peptide C as compared to individuals with the T-allele (P = 0.006). Subjects carrying the T-allele showed a lower gene PCK1 expression as compared with carriers of the C/C genotype (P = 0.015). The PCK1 rs2179706 polymorphism interacts with plasma concentration of n - 3 PUFA levels modulating insulin resistance in MetS subjects. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Acculturation and Plasma Fatty Acid Concentrations in Hispanic and Chinese-American Adults: The Multi-Ethnic Study of Atherosclerosis

PubMed Central

Diep, Cassandra S.; Lemaitre, Rozenn N.; Chen, Tzu-An; Baranowski, Tom; Lutsey, Pamela L.; Manichaikul, Ani W.; Rich, Stephen S.; St-Jules, David E.; Steffen, Brian T.; Tsai, Michael Y.; Siscovick, David S.; Frazier-Wood, Alexis C.

2016-01-01

Background Acculturation to the U.S. is associated with increased risk of cardiovascular disease, but the etiologic pathways are not fully understood. Plasma fatty acid levels exhibit ethnic differences and are emerging as biomarkers and predictors of cardiovascular disease risk. Thus, plasma fatty acids may represent one pathway underlying the association between acculturation and cardiovascular disease. We investigated the cross-sectional relationship between acculturation and plasma phospholipid fatty acids in a diverse sample of Hispanic- and Chinese-American adults. Methods and Findings Participants included 377 Mexican, 320 non-Mexican Hispanic, and 712 Chinese adults from the Multi-Ethnic Study of Atherosclerosis, who had full plasma phospholipid assays and acculturation information. Acculturation was determined from three proxy measures: nativity, language spoken at home, and years in the U.S., with possible scores ranging from 0 (least acculturated) to 5 (most acculturated) points. α-Linolenic acid, linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid were measured in fasting plasma. Linear regression models were conducted in race/ethnicity-stratified analyses, with acculturation as the predictor and plasma phospholipid fatty acids as the outcome variables. We ran secondary analyses to examine associations between acculturation and dietary fatty acids for comparison. Covariates included age, gender, education, and income. Contrary to our hypothesis, no statistically significant associations were detected between acculturation and plasma phospholipid fatty acids for Chinese, non-Mexican Hispanic, or Mexican participants. However, acculturation was related to dietary total n-6 fatty acids and dietary n-3/n-6 ratios in expected directions for Mexican, non-Mexican Hispanic, and combined Hispanic participants. In Chinese individuals, acculturation was unexpectedly associated with lower arachidonic acid intake. Conclusion Absence of associations between acculturation and plasma phospholipid fatty acids suggests that changes in the plasma phospholipid fatty acids studied do not account for the observed associations of acculturation to the U.S. and cardiovascular disease risk. Similar findings were observed for eicosapentaenoic acid and docosahexaenoic acid, when using dietary intake. However, the observed associations between dietary n-6 fatty acids and acculturation in Hispanic individuals suggest that dietary intake may be more informative than phospholipids when investigating acculturation effects. In Chinese individuals, acculturation may have a possible protective effect through decreased arachidonic acid intake. Further research on dietary fatty acids and other cardiovascular disease biomarkers is needed to identify possible etiologic mechanisms between acculturation and cardiovascular disease. PMID:26872329

Low n-6:n-3 fatty acid ratio, with fish- or flaxseed oil, in a high fat diet improves plasma lipids and beneficially alters tissue fatty acid composition in mice.

PubMed

Riediger, Natalie D; Othman, Rgia; Fitz, Evelyn; Pierce, Grant N; Suh, Miyoung; Moghadasian, Mohammed H

2008-04-01

Health benefits from low n-6:n-3 fatty acid (FA) ratio on cardiovascular risk have been shown. However, the impact of the source of n-3 FAs has not been fully investigated. Our purpose was to investigate cardiovascular benefits of oils with a low ratio of n-6:n-3 FAs, but different sources of n-3 FAs in C57BL/6 mice. Twenty-one mice were divided into 3 groups (n=7) and fed a diet supplemented with either a fish or flaxseed oil-based 'designer oils' with an approximate n-6:n-3 FA ratio of 2/1 or with a safflower-oil-based diet with a ratio of 25/1, for 16 weeks. Plasma lipids and fatty acid profile of the liver tissue were characterized. Compared to baseline, plasma triacylglycerol levels declined (>50%) in all groups by week 4. Plasma cholesterol levels were reduced in both fish and flax groups by 27% and 36%, respectively, as compared to controls at endpoint. The levels of EPA and DHA in liver phospholipids were significantly increased in both fish and flax groups as compared to the control group, with more profound increases in the fish group. Arachidonic acid levels were similarly decreased in the liver tissues from both fish and flax groups as compared to controls. Our data suggest that health benefits may be achieved by lowering dietary n-6:n-3 FA even in a high fat diet medium.

Bioavailability of an R-α-Lipoic Acid/γ-Cyclodextrin Complex in Healthy Volunteers

PubMed Central

Ikuta, Naoko; Okamoto, Hinako; Furune, Takahiro; Uekaji, Yukiko; Terao, Keiji; Uchida, Ryota; Iwamoto, Kosuke; Miyajima, Atsushi; Hirota, Takashi; Sakamoto, Norihiro

2016-01-01

R-α-lipoic acid (R-LA) is a cofactor of mitochondrial enzymes and a very strong antioxidant. R-LA is available as a functional food ingredient but is unstable against heat or acid. Stabilized R-LA was prepared through complexation with γ-cyclodextrin (CD), yielding R-LA/CD. R-LA/CD was orally administered to six healthy volunteers and showed higher plasma levels with an area under the plasma concentration-time curve that was 2.5 times higher than that after oral administration of non-complexed R-LA, although the time to reach the maximum plasma concentration and half-life did not differ. Furthermore, the plasma glucose level after a single oral administration of R-LA/CD or R-LA was not affected and no side effects were observed. These results indicate that R-LA/CD could be easily absorbed in the intestine. In conclusion, γ-CD complexation is a promising technology for delivering functional but unstable ingredients like R-LA. PMID:27314343

Sweat Facilitated Amino Acid Losses in Male Athletes during Exercise at 32-34°C.

PubMed

Dunstan, R Hugh; Sparkes, Diane L; Dascombe, Benjamin J; Macdonald, Margaret M; Evans, Craig A; Stevens, Christopher J; Crompton, Marcus J; Gottfries, Johan; Franks, Jesse; Murphy, Grace; Wood, Ryan; Roberts, Timothy K

2016-01-01

Sweat contains amino acids and electrolytes derived from plasma and athletes can lose 1-2L of sweat per hour during exercise. Sweat may also contain contributions of amino acids as well as urea, sodium and potassium from the natural moisturizing factors (NMF) produced in the stratum corneum. In preliminary experiments, one participant was tested on three separate occasions to compare sweat composition with surface water washings from the same area of skin to assess contributions from NMF. Two participants performed a 40 minute self-paced cycle session with sweat collected from cleansed skin at regular intervals to assess the contributions to the sweat load from NMF over the period of exercise. The main study investigated sweat amino acid composition collected from nineteen male athletes following standardised endurance exercise regimes at 32-34°C and 20-30% RH. Plasma was also collected from ten of the athletes to compare sweat and plasma composition of amino acids. The amino acid profiles of the skin washings were similar to the sweat, suggesting that the NMF could contribute certain amino acids into sweat. Since the sweat collected from athletes contained some amino acid contributions from the skin, this fluid was subsequently referred to as "faux" sweat. Samples taken over 40 minutes of exercise showed that these contributions diminished over time and were minimal at 35 minutes. In the main study, the faux sweat samples collected from the athletes with minimal NMF contributions, were characterised by relatively high levels of serine, histidine, ornithine, glycine and alanine compared with the corresponding levels measured in the plasma. Aspartic acid was detected in faux sweat but not in the plasma. Glutamine and proline were lower in the faux sweat than plasma in all the athletes. Three phenotypic groups of athletes were defined based on faux sweat volumes and composition profiles of amino acids with varying relative abundances of histidine, serine, glycine and ornithine. It was concluded that for some individuals, faux sweat resulting from exercise at 32-34°C and 20-30% RH posed a potentially significant source of amino acid loss.

Sweat Facilitated Amino Acid Losses in Male Athletes during Exercise at 32-34°C

PubMed Central

Dunstan, R. Hugh; Sparkes, Diane L.; Dascombe, Benjamin J.; Macdonald, Margaret M.; Evans, Craig A.; Stevens, Christopher J.; Crompton, Marcus J.; Gottfries, Johan; Franks, Jesse; Murphy, Grace; Wood, Ryan; Roberts, Timothy K.

2016-01-01

Sweat contains amino acids and electrolytes derived from plasma and athletes can lose 1-2L of sweat per hour during exercise. Sweat may also contain contributions of amino acids as well as urea, sodium and potassium from the natural moisturizing factors (NMF) produced in the stratum corneum. In preliminary experiments, one participant was tested on three separate occasions to compare sweat composition with surface water washings from the same area of skin to assess contributions from NMF. Two participants performed a 40 minute self-paced cycle session with sweat collected from cleansed skin at regular intervals to assess the contributions to the sweat load from NMF over the period of exercise. The main study investigated sweat amino acid composition collected from nineteen male athletes following standardised endurance exercise regimes at 32–34°C and 20–30% RH. Plasma was also collected from ten of the athletes to compare sweat and plasma composition of amino acids. The amino acid profiles of the skin washings were similar to the sweat, suggesting that the NMF could contribute certain amino acids into sweat. Since the sweat collected from athletes contained some amino acid contributions from the skin, this fluid was subsequently referred to as “faux” sweat. Samples taken over 40 minutes of exercise showed that these contributions diminished over time and were minimal at 35 minutes. In the main study, the faux sweat samples collected from the athletes with minimal NMF contributions, were characterised by relatively high levels of serine, histidine, ornithine, glycine and alanine compared with the corresponding levels measured in the plasma. Aspartic acid was detected in faux sweat but not in the plasma. Glutamine and proline were lower in the faux sweat than plasma in all the athletes. Three phenotypic groups of athletes were defined based on faux sweat volumes and composition profiles of amino acids with varying relative abundances of histidine, serine, glycine and ornithine. It was concluded that for some individuals, faux sweat resulting from exercise at 32–34°C and 20–30% RH posed a potentially significant source of amino acid loss. PMID:27936120

Plasma homovanillic acid, plasma anti-D1 and -D2 dopamine-receptor activity, and negative symptoms in chronically mediated schizophrenia.

PubMed

Suzuki, E; Kanba, S; Nibuya, M; Koshikawa, H; Nakaki, T; Yagi, G

1992-02-15

We have investigated the relationship between the concentration of homovanillic acid in human plasma (pHVA) and plasma anti-D1 and anti-D2 dopamine receptor activity in chronic schizophrenic patients whose neuroleptic dosage was changed. The change in pHVA level correlated with that in anti-D1, not anti-D2 activity, thus suggesting that the neuroleptic-induced changes in pHVA concentration may be associated with the blocking of D1- as well as D2- receptors. The change of scores on the Scale for the Assessment of Negative Symptoms did not significantly correlate with changes in anti-D1 or anti-D2 activity, but did so correlated with the change in pHVA level.

Amino Acid Concentrations in HIV-Infected Youth Compared to Healthy Controls and Associations with CD4 Counts and Inflammation.

PubMed

Ziegler, Thomas R; Judd, Suzanne E; Ruff, Joshua H; McComsey, Grace A; Eckard, Allison Ross

2017-07-01

Amino acids play critical roles in metabolism, cell function, body composition and immunity, but little data on plasma amino acid concentrations in HIV are available. We evaluated plasma amino acid concentrations and associations with CD4 counts and inflammatory biomarkers in HIV-infected youth. HIV-infected subjects with a high (≥500 cells/mm 3 ) and low (<500 cells/mm 3 ) current CD4 + T cell counts were compared to one another and to a matched healthy control group. Plasma concentrations of 19 amino acids were determined with an amino acid analyzer. Plasma levels of interleukin-6, tumor necrosis factor receptor-I, and soluble vascular cellular adhesion molecule-I were also measured. Seventy-nine HIV-infected subjects (40 and 39 with high and low CD4 + T cell counts, respectively) and 40 controls were included. There were no differences in amino acid concentrations between HIV-infected subjects with high or low CD4 + T cell counts. When combined, the HIV-infected group exhibited significantly lower median plasma concentrations compared to controls for total, essential, branched-chain and sulfur amino acids, as well as for 12 individual amino acids. Glutamate was the only amino acid that was higher in the HIV-infected group. There were no significant correlations between amino acid endpoints and inflammatory biomarkers for either HIV-infected group or controls. Plasma amino acid concentrations were lower in HIV-infected youth compared to healthy controls, regardless of immune status, while glutamate concentrations were elevated. These findings can inform future interventional studies designed to improve metabolic and clinical parameters influenced by amino acid nutriture.

Effect of oral contraceptive agents on nutrients: II. Vitamins.

PubMed

Prasad, A S; Oberleas, D; Moghissi, K S; Stryker, J C; Lei, K Y

1975-04-01

Clinical, biochemical and nutritional data were collected from a large population of women using oral contraceptive agents. Higher incidence of abnormal clinical signs related to malnutrition were observed in the lower (B) as compared to the higher (A) socioeconomic groups, and also in the nonsupplemented groups as compared to the supplemented groups in the B subjects. As a rule the intake of oral contraceptive agent subjects of vitamin A, C, B6 and folic acid did not differ from that of the controls As expected, subjects from the supplemented groups had higher intake of vitamin A, C, B6, thiamin, riboflavin and folic acid, and A groups had higher intake of vitamin C, B6, riboflavin and folic acid. Increased plasma vitamin A and decreased carotene levels were observed in oral contraceptive agent users. In general oral contraceptive agents had little or no effect on plasma ascorbic acid. Urinary excretion of both thiamin and riboflavin in subjects using oral contraceptive agents were lower in A groups. Erythrocyte folate and plasma pyridoxal phosphate was decreased in A groups due to oral contraceptive agents. Subjects who took supplements had higher levels of plasma vitamin A, ascorbic acid and folate. But urinary thiamin and riboflavin were higher only in group A subjects who took supplements.

Plasma and serum from nonfasting men and women differ in their lipidomic profiles.

PubMed

Ishikawa, Masaki; Tajima, Yoko; Murayama, Mayumi; Senoo, Yuya; Maekawa, Keiko; Saito, Yoshiro

2013-01-01

Biomarkers will play important roles in disease diagnosis, drug development, and the proper use of drugs. Blood is considered the best biofluid for biomarker research because it is easy to access and a wealth of data are available. However, previous studies revealed that several ionic metabolites showed different levels (including presence or absence) in plasma and serum. Thus, attention should be paid to selecting the best biofluid for biomarker exploration. Many lipid molecules have biological significance and thus would be candidate biomarkers. However, no comprehensive study revealing differences in lipid metabolite levels between plasma and serum has been undertaken. Furthermore, gender differences have not been reported. To clarify the difference in the levels of lipid metabolites between human plasma and serum from both genders, we performed lipid metabolomic analysis using liquid chromatography-mass spectrometry-based systems for phospholipids (PLs), lysoPLs, sphingomyelins, ceramides and oxidative fatty acids. Our results revealed that most of the lipid metabolites were present at similar levels in plasma and serum and in males and females. However, several oxidative fatty acid metabolites showed differences. Of the metabolites related to clotting processes, three showed higher levels in serum than in plasma, and three were detected only in serum. Furthermore, four metabolites were present at different levels between males and females, and two were detected only in males. Thus, attention should be paid to the selection of plasma or serum when utilizing these lipid metabolites as biomarkers.

Effect of a fish oil-containing beverage on changes in plasma lipid fatty acids in patients with malabsorption

PubMed Central

McCowen, Karen C.; Ling, Pei-Ra; Ollero, Mario; Tawa, Nicholas; Bistrian, Bruce R.

2015-01-01

Background The aim of this pilot study was to assess tolerance of a beverage containing ω-3 fatty acids (fish oil) in patients with malabsorption receiving chronic parenteral nutrition (PN). We wanted to determine whether fish oil could be absorbed and incorporated into plasma fatty acids, and reduce markers of inflammation. Methods This was a small intervention study in home-dwelling PN-dependent patients with chronic malabsorption. Ten patients were provided a drink containing 1.5g of fish oil per day for 12 weeks. Baseline and post-supplement serum fatty acid profiles were compared. Results Five of 10 patients withdrew from the study due to gastrointestinal side effects, principally worsened diarrhea, associated with the supplement. Modest increases were found in 20:5ω-3, 22:5ω-3, and 22:6ω-3 levels in both phospholipids and triglycerides in plasma (all p<0.05). In phospholipids, a reduced arachidonic acid level was seen (p=0.02). These changes were not sufficient to effect improvements in serum tumor necrosis factor-alpha (TNFα), soluble TNF receptor, c-reactive protein or Interleukin-6. Conclusions Some patients with severe malabsorption can absorb oral ω-3 fatty acid supplements and can incorporate these fatty acids into serum phospholipids and triglycerides. However, side effects are very common, and no anti-inflammatory effect was found, presumably related to the modest level of fatty acid change. PMID:20962312

Effect of ethanol on metabolism of purine bases (hypoxanthine, xanthine, and uric acid).

PubMed

Yamamoto, Tetsuya; Moriwaki, Yuji; Takahashi, Sumio

2005-06-01

There are many factors that contribute to hyperuricemia, including obesity, insulin resistance, alcohol consumption, diuretic use, hypertension, renal insufficiency, genetic makeup, etc. Of these, alcohol (ethanol) is the most important. Ethanol enhances adenine nucleotide degradation and increases lactic acid level in blood, leading to hyperuricemia. In beer, purines also contribute to an increase in plasma uric acid. Although rare, dehydration and ketoacidosis (due to ethanol ingestion) are associated with the ethanol-induced increase in serum uric acid levels. Ethanol also increases the plasma concentrations and urinary excretion of hypoxanthine and xanthine via the acceleration of adenine nucleotide degradation and a possible weak inhibition of xanthine dehydrogenase activity. Since many factors such as the ALDH2*1 gene and ADH2*2 gene, daily drinking habits, exercise, and dehydration enhance the increase in plasma concentration of uric acid induced by ethanol, it is important to pay attention to these factors, as well as ingested ethanol volume, type of alcoholic beverage, and the administration of anti-hyperuricemic agents, to prevent and treat ethanol-induced hyperuricemia.

Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men.

PubMed

Stancáková, Alena; Civelek, Mete; Saleem, Niyas K; Soininen, Pasi; Kangas, Antti J; Cederberg, Henna; Paananen, Jussi; Pihlajamäki, Jussi; Bonnycastle, Lori L; Morken, Mario A; Boehnke, Michael; Pajukanta, Päivi; Lusis, Aldons J; Collins, Francis S; Kuusisto, Johanna; Ala-Korpela, Mika; Laakso, Markku

2012-07-01

We investigated the association of glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes with amino acid levels in the population-based Metabolic Syndrome in Men (METSIM) Study, including 9,369 nondiabetic or newly diagnosed type 2 diabetic Finnish men. Plasma levels of eight amino acids were measured with proton nuclear magnetic resonance spectroscopy. Increasing fasting and 2-h plasma glucose levels were associated with increasing levels of several amino acids and decreasing levels of histidine and glutamine. Alanine, leucine, isoleucine, tyrosine, and glutamine predicted incident type 2 diabetes in a 4.7-year follow-up of the METSIM Study, and their effects were largely mediated by insulin resistance (except for glutamine). We also found significant correlations between insulin sensitivity (Matsuda insulin sensitivity index) and mRNA expression of genes regulating amino acid degradation in 200 subcutaneous adipose tissue samples. Only 1 of 43 risk single nucleotide polymorphisms for type 2 diabetes or hyperglycemia, the glucose-increasing major C allele of rs780094 of GCKR, was significantly associated with decreased levels of alanine and isoleucine and elevated levels of glutamine. In conclusion, the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia, reflecting, at least in part, insulin resistance. Only one single nucleotide polymorphism regulating hyperglycemia was significantly associated with amino acid levels.

Hyperglycemia and a Common Variant of GCKR Are Associated With the Levels of Eight Amino Acids in 9,369 Finnish Men

PubMed Central

Stančáková, Alena; Civelek, Mete; Saleem, Niyas K.; Soininen, Pasi; Kangas, Antti J.; Cederberg, Henna; Paananen, Jussi; Pihlajamäki, Jussi; Bonnycastle, Lori L.; Morken, Mario A.; Boehnke, Michael; Pajukanta, Päivi; Lusis, Aldons J.; Collins, Francis S.; Kuusisto, Johanna; Ala-Korpela, Mika; Laakso, Markku

2012-01-01

We investigated the association of glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes with amino acid levels in the population-based Metabolic Syndrome in Men (METSIM) Study, including 9,369 nondiabetic or newly diagnosed type 2 diabetic Finnish men. Plasma levels of eight amino acids were measured with proton nuclear magnetic resonance spectroscopy. Increasing fasting and 2-h plasma glucose levels were associated with increasing levels of several amino acids and decreasing levels of histidine and glutamine. Alanine, leucine, isoleucine, tyrosine, and glutamine predicted incident type 2 diabetes in a 4.7-year follow-up of the METSIM Study, and their effects were largely mediated by insulin resistance (except for glutamine). We also found significant correlations between insulin sensitivity (Matsuda insulin sensitivity index) and mRNA expression of genes regulating amino acid degradation in 200 subcutaneous adipose tissue samples. Only 1 of 43 risk single nucleotide polymorphisms for type 2 diabetes or hyperglycemia, the glucose-increasing major C allele of rs780094 of GCKR, was significantly associated with decreased levels of alanine and isoleucine and elevated levels of glutamine. In conclusion, the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia, reflecting, at least in part, insulin resistance. Only one single nucleotide polymorphism regulating hyperglycemia was significantly associated with amino acid levels. PMID:22553379

Hexadecenoic fatty acid isomers: a chemical biology approach for human plasma biomarker development.

PubMed

Sansone, Anna; Melchiorre, Michele; Chatgilialoglu, Chryssostomos; Ferreri, Carla

2013-11-18

Hexadecenoic fatty acids are monounsaturated lipid components, which are interesting targets of plasma lipidomic studies and biomarker development. The main positional isomers, palmitoleic (9-cis-16:1) and sapienic acids (6-cis-16:1), have an endogenous origin from palmitic acid, the former being recognized as a component of adipose tissue with signaling activity, whereas the latter is mainly reported as a component of sebum. The trans 16:1 isomers are attributed so far to dietary sources of industrial and dairy fats, whereas the endogenous formation due to the free radical-mediated isomerization can represent an emerging, yet unexplored, pathway connected to cellular stress. Herein, we report a chemical biology approach for the development of hexadecenoic fatty acids as plasma biomarkers, with the first synthesis of 6-trans-16:1 and the efficient analytical setup with unambiguous assignment of 16:1 double bond position and geometry, which was applied to human commercial LDL and plasma cholesteryl esters. Sapienic acid was identified together with its geometrical trans isomer for the first time. The quantitation of hexadecenoic fatty acid isomers evidenced their different levels in the two lipid classes and LDL fractions, making us foresee interesting applications to the metabolic evaluation of fatty acid pathways. These findings open new perspectives for plasma lipidomics involving monounsaturated fatty acids, highlighting future developments for their evaluation in different health conditions including free radical stress.

Discriminative Ability of Plasma Branched-Chain Amino Acid Levels for Glucose Intolerance in Families At Risk for Type 2 Diabetes.

PubMed

Jainandunsing, Sjaam; Wattimena, J L Darcos; Verhoeven, Adrie J M; Langendonk, Janneke G; Rietveld, Trinet; Isaacs, Aaron J; Sijbrands, Eric J G; de Rooij, Felix W M

2016-04-01

Insulin resistance and glucose intolerance have been associated with increased plasma levels of branched-chain amino acids (BCAA). BCAA levels do not predict T2DM in the population. We determined the discriminative ability of fasting BCAA levels for glucose intolerance in nondiabetic relatives of patients with T2DM of two different ethnicities. Based on oral glucose tolerance test (OGTT), first-degree relatives of patients with T2DM were categorized as normal glucose tolerance, prediabetes, or T2DM. Included were 34, 12, and 18 Caucasian and 22, 12, and 23 Asian Indian participants, respectively. BCAA levels were measured in fasting plasma together with alanine, phenylalanine, and tyrosine. Insulin sensitivity and beta-cell function were assessed by indices derived from an extended OGTT and their relationship with plasma BCAA levels was assessed in multivariate regression analysis. The value of the amino acids for discriminating prediabetes among nondiabetic family members was determined with the area under the curve of receiver-operated characteristics (c-index). BCAA levels were higher in diabetic than in normoglycemic family members in the Caucasians (P = 0.001) but not in the Asian Indians. In both groups, BCAA levels were associated with waist-hip ratio (β = 0.31; P = 0.03 and β = 0.42; P = 0.001, respectively) but not with indices of insulin sensitivity or beta-cell function. The c-index of BCAA for discriminating prediabetes among nondiabetic participants was 0.83 and 0.74 in Caucasians and Asian Indians, respectively, which increased to 0.84 and 0.79 by also including the other amino acids. The c-index of fasting glucose for discriminating prediabetes increased from 0.91 to 0.92 in Caucasians and 0.85 to 0.97 (P = 0.04) in Asian Indians by inclusion of BCAA+alanine, phenylalanine, and tyrosine. Adding fasting plasma BCAA levels, combined with phenylalanine, tyrosine and alanine to fasting glucose improved discriminative ability for the prediabetic state within Asian Indian families at risk for T2DM. BCAA levels may serve as biomarkers for early development of glucose intolerance in these families.

Effect of urinary pH and nicotine excretion rate on plasma nicotine during cigarette smoking and chewing nicotine gum

PubMed Central

Feyerabend, C.; Russell, M. A. H.

1978-01-01

1 Plasma nicotine levels produced by chewing nicotine gum were compared with those obtained by cigarette smoking under conditions of controlled urinary pH. 2 Although absorption was slower, plasma levels comparable to cigarette smoking were built up on 4 mg (but not 2 mg) nicotine gum. 3 Urinary excretion of nicotine was influenced markedly by pH and the rate of urine flow. 4 Plasma nicotine was higher under alkaline compared to acidic conditions (P < 0.001) but the rate of urinary nicotine excretion appeared to have little effect on the plasma level.

Application of GC/MS-based metabonomic profiling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats

PubMed Central

Zhang, Qi; Wang, Guang-ji; A, Ji-ye; Wu, Di; Zhu, Ling-ling; Ma, Bo; Du, Yu

2009-01-01

Aim: To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia. Methods: EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA). Results: The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and –treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and–treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB. Conclusion: EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia. PMID:19960012

Application of GC/MS-based metabonomic profiling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats.

PubMed

Zhang, Qi; Wang, Guang-ji; A, Ji-ye; Wu, Di; Zhu, Ling-ling; Ma, Bo; Du, Yu

2009-12-01

To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia. EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA). The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and -treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and-treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB. EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia.

Effect of 50 Hz electric field in diacylglycerol acyltransferase mRNA expression level and plasma concentration of triacylglycerol, free fatty acid, phospholipid and total cholesterol

PubMed Central

2012-01-01

Background The effects of exposure to a 50 Hz electric field (EF) on plasma level of triacylglycerol, free fatty acids, total cholesterol and phospholipid and mRNA expression level of diacylglycerol acyltransferase (DGAT) 1 and 2 in liver and intestines from C57BL/6 J mice were studied. Methods The test was based on comparison between mice post treated with 50 Hz EF of 45 kV/m intensity for 30 min per day for 11 days or without EF. DGATs mRNA expression was analyzed by real-time quantitative polymerase chain reaction. Results There was no difference in the gene expression level of DGAT1 in liver and intestines. The DGAT2 gene expression level in liver derived from mice treated with EF was significantly lower than those in the control (P < 0.001). Both plasma total cholesterol (P < 0.01) and phospholipid (P < 0.05) in the group exposed to EF were lower than those in the control, but there was no difference in triacylglycerol or free fatty acid levels. Conclusion Exposure to 50 Hz EF decrease the plasma levels of total cholesterol and phospholipids, and downregulated DGAT2 mRNA expression in liver. The mechanisms for the effects of EF on lipid metabolism are not well understand yet, but altered DGAT2 activity may be involved. PMID:22676350

Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission.

PubMed

Arora, Tulika; Velagapudi, Vidya; Pournaras, Dimitri J; Welbourn, Richard; le Roux, Carel W; Orešič, Matej; Bäckhed, Fredrik

2015-01-01

Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3), which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission.

Roux-en-Y Gastric Bypass Surgery Induces Early Plasma Metabolomic and Lipidomic Alterations in Humans Associated with Diabetes Remission

PubMed Central

Pournaras, Dimitri J.; Welbourn, Richard; le Roux, Carel W.; Orešič, Matej; Bäckhed, Fredrik

2015-01-01

Roux-en-Y gastric bypass (RYGB) is an effective method to attain sustained weight loss and diabetes remission. We aimed to elucidate early changes in the plasma metabolome and lipidome after RYGB. Plasma samples from 16 insulin-resistant morbidly obese subjects, of whom 14 had diabetes, were subjected to global metabolomics and lipidomics analysis at pre-surgery and 4 and 42 days after RYGB. Metabolites and lipid species were compared between time points and between subjects who were in remission and not in remission from diabetes 2 years after surgery. We found that the variables that were most discriminatory between time points were decanoic acid and octanoic acid, which were elevated 42 days after surgery, and sphingomyelins (18:1/21:0 and 18:1/23:3), which were at their lowest level 42 days after surgery. Insulin levels were lower at 4 and 42 days after surgery compared with pre-surgery levels. At 4 days after surgery, insulin levels correlated positively with metabolites of branched chain and aromatic amino acid metabolism and negatively with triglycerides with long-chain fatty acids. Of the 14 subjects with diabetes prior to surgery, 7 were in remission 2 years after surgery. The subjects in remission displayed higher pre-surgery levels of tricarboxylic acid cycle intermediates and triglycerides with long-chain fatty acids compared with subjects not in remission. Thus, metabolic alterations are induced soon after surgery and subjects with diabetes remission differ in the metabolic profiles at pre- and early post-surgery time points compared to patients not in remission. PMID:25946120

Effect of a Diet Enriched with Fresh Coconut Saturated Fats on Plasma Lipids and Erythrocyte Fatty Acid Composition in Normal Adults.

PubMed

Nagashree, Rokkam Shankar; Manjunath, N K; Indu, M; Ramesh, M; Venugopal, V; Sreedhar, P; Pavithra, N; Nagendra, Hongasandra R

2017-07-01

The objective of this study was to compare the effects of increased saturated fatty acid (SFA) (provided by fresh coconut) versus monounsaturated fatty acid (MUFA) intake (provided by a combination of groundnuts and groundnut oil) on plasma lipids and erythrocyte fatty acid (EFA) composition in healthy adults. Fifty-eight healthy volunteers, randomized into 2 groups, were provided standardized diet along with 100 g fresh coconut or groundnuts and groundnut oil combination for 90 days in a Yoga University. Fasting blood samples were collected before and after the intervention period for the measurement of plasma lipids and EFA profile. Coconut diet increased low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels significantly. In contrast, the groundnut diet decreased total cholesterol (TC), mainly due to a decrease in HDL levels. There were no differences in the major SFA of erythrocytes in either group. However, coconut consumption resulted in an increase in C14:0 and C24:0 along with a decrease in levels of C18:1 n9 (oleic acid). There was a significant increase in levels of C20:3 n6 (dihomo-gamma linolenic acid, DGLA). Consumption of SFA-rich coconut for 3 months had no significant deleterious effect on erythrocytes or lipid-related factors compared to groundnut consumption. On the contrary, there was an increase in the anti-atherogenic HDL levels and anti-inflammatory precursor DGLA in erythrocyte lipids. This suggests that coconut consumption may not have any deleterious effects on cardiovascular risk in normal subjects.

Transfer of omega-3 fatty acids across the blood-brain barrier after dietary supplementation with a docosahexaenoic acid-rich omega-3 fatty acid preparation in patients with Alzheimer's disease: the OmegAD study.

PubMed

Freund Levi, Y; Vedin, I; Cederholm, T; Basun, H; Faxén Irving, G; Eriksdotter, M; Hjorth, E; Schultzberg, M; Vessby, B; Wahlund, L-O; Salem, N; Palmblad, J

2014-04-01

Little is known about the transfer of essential fatty acids (FAs) across the human blood-brain barrier (BBB) in adulthood. In this study, we investigated whether oral supplementation with omega-3 (n-3) FAs would change the FA profile of the cerebrospinal fluid (CSF). A total of 33 patients (18 receiving the n-3 FA supplement and 15 receiving placebo) were included in the study. These patients were participants in the double-blind, placebo-controlled randomized OmegAD study in which 204 patients with mild Alzheimer's disease (AD) received 2.3 g n-3 FA [high in docosahexaenoic acid (DHA)] or placebo daily for 6 months. CSF FA levels were related to changes in plasma FA and to CSF biomarkers of AD and inflammation. At 6 months, the n-3 FA supplement group displayed significant increases in CSF (and plasma) eicosapentaenoic acid (EPA), DHA and total n-3 FA levels (P < 0.01), whereas no changes were observed in the placebo group. Changes in CSF and plasma levels of EPA and n-3 docosapentaenoic acid were strongly correlated, in contrast to those of DHA. Changes in DHA levels in CSF were inversely correlated with CSF levels of total and phosphorylated tau, and directly correlated with soluble interleukin-1 receptor type II. Thus, the more DHA increased in CSF, the greater the change in CSF AD/inflammatory biomarkers. Oral supplementation with n-3 FAs conferred changes in the n-3 FA profile in CSF, suggesting transfer of these FAs across the BBB in adults. © 2013 The Association for the Publication of the Journal of Internal Medicine.

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study.

PubMed

Hammad, Samar M; Baker, Nathaniel L; El Abiad, Jad M; Spassieva, Stefanka D; Pierce, Jason S; Rembiesa, Barbara; Bielawski, Jacek; Lopes-Virella, Maria F; Klein, Richard L

2017-03-01

Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80), with and without symptoms of neuropathy, were investigated. Patient-determined neuropathy was based on 15-item self-administered questionnaire (Michigan Neuropathy Screening Instrument) developed to assess distal symmetrical peripheral neuropathy in diabetes. Patients who scored ≥4, or reported inability to sense their feet during walking or to distinguish hot from cold water while bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin, hexosyl- and lactosylceramide species, and amino acids were measured and analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24- and C26-ceramide were higher in patients with neuropathy than those without neuropathy. Cysteine was higher in patients with neuropathy. No differences in other sphingolipids or amino acids were detected. The covariate-adjusted Odds Ratios of positive patient-reported neuropathy was associated with increased levels of deoxy-C24-, and deoxy-C24:1-ceramide; C22-, C24-, and C26-ceramide; and cysteine. Plasma deoxy-ceramide and ceramide species may have potential diagnostic and prognostic significance in diabetic neuropathy.

Increased Plasma Levels of Select Deoxy-ceramide and Ceramide Species are Associated with Increased Odds of Diabetic Neuropathy in Type 1 Diabetes: A Pilot Study

PubMed Central

Baker, Nathaniel L.; El Abiad, Jad M.; Spassieva, Stefanka D.; Pierce, Jason S.; Rembiesa, Barbara; Bielawski, Jacek; Lopes-Virella, Maria F.; Klein, Richard L.; Investigators, DCCT/EDIC Group of

2017-01-01

Plasma deoxy-sphingoid bases are elevated in type 2 diabetes patients and correlate with the stage of diabetic distal sensorimotor polyneuropathy; however, associations between deoxy-sphingolipids (DSL) and neuropathy in type 1 diabetes have not been examined. The primary aim of this exploratory pilot study was to assess the associations between multiple sphingolipid species including DSL and free amino acids and the presence of symptomatic neuropathy in a DCCT/EDIC type 1 diabetes subcohort. Using mass spectroscopy, plasma levels of DSL and free amino acids in DCCT/EDIC type 1 diabetes participants (n = 80), with and without symptoms of neuropathy, were investigated. Patient-determined neuropathy was based on 15-item self-administered questionnaire (Michigan Neuropathy Screening Instrument) developed to assess distal symmetrical peripheral neuropathy in diabetes. Patients who scored ≥4, or reported inability to sense their feet during walking or to distinguish hot from cold water while bathing were considered neuropathic. Plasma levels of ceramide, sphingomyelin, hexosyl- and lactosylceramide species, and amino acids were measured and analyzed relative to neuropathy status in the patient. Deoxy-C24-ceramide, C24- and C26-ceramide were higher in patients with neuropathy than those without neuropathy. Cysteine was higher in patients with neuropathy. No differences in other sphingolipids or amino acids were detected. The covariate-adjusted Odds Ratios of positive patient-reported neuropathy was associated with increased levels of deoxy-C24-, and deoxy-C24:1-ceramide; C22-, C24-, and C26-ceramide; and cysteine. Plasma deoxy-ceramide and ceramide species may have potential diagnostic and prognostic significance in diabetic neuropathy. PMID:27388466

Differential effects of military training on fat-free mass and plasma amino acid adaptations in men and women.

PubMed

Margolis, Lee M; Pasiakos, Stefan M; Karl, J Philip; Rood, Jennifer C; Cable, Sonya J; Williams, Kelly W; Young, Andrew J; McClung, James P

2012-12-18

Fat-free mass (FFM) adaptations to physical training may differ between sexes based on disparities in fitness level, dietary intake, and levels of plasma amino acids (AA). This investigation aimed to determine FFM and plasma AA responses to military training, examine whether adaptations differ between male and female recruits, and explore potential associations between FFM and AA responses to training. Body composition and plasma AA levels were assessed in US Army recruits (n = 209, 118 males, 91 females) before (baseline) and every three weeks during basic combat training (BCT), a 10-week military training course. Body weight decreased in men but remained stable in women during BCT (sex-by-time interaction, P < 0.05). Fifty-eight percent of recruits gained FFM during BCT, with more (P < 0.05) females (88%) gaining FFM than males (36%). Total plasma AA increased (P < 0.05) during BCT, with greater (P < 0.05) increases observed in females (17%) then in males (4%). Essential amino acids (EAA) and branched-chain amino acids (BCAA) were increased (P < 0.05) in females but did not change in males (sex-by-time interaction, P < 0.05). Independent of sex, changes in EAA (r = 0.34) and BCAA (r = 0.27) from baseline were associated with changes in FFM (P < 0.05); greater (P < 0.05) increases in AA concentrations were observed for those who gained FFM. Increases in FFM and plasma AA suggest that BCT elicits a more pronounced anabolic response in women compared to men, which may reflect sex-specific differences in the relative intensity of the combined training and physiological stimulus associated with BCT.

Differential Effects of Military Training on Fat-Free Mass and Plasma Amino Acid Adaptations in Men and Women

PubMed Central

Margolis, Lee M.; Pasiakos, Stefan M.; Karl, J. Philip; Rood, Jennifer C.; Cable, Sonya J.; Williams, Kelly W.; Young, Andrew J.; McClung, James P.

2012-01-01

Fat-free mass (FFM) adaptations to physical training may differ between sexes based on disparities in fitness level, dietary intake, and levels of plasma amino acids (AA). This investigation aimed to determine FFM and plasma AA responses to military training, examine whether adaptations differ between male and female recruits, and explore potential associations between FFM and AA responses to training. Body composition and plasma AA levels were assessed in US Army recruits (n = 209, 118 males, 91 females) before (baseline) and every three weeks during basic combat training (BCT), a 10-week military training course. Body weight decreased in men but remained stable in women during BCT (sex-by-time interaction, P < 0.05). Fifty-eight percent of recruits gained FFM during BCT, with more (P < 0.05) females (88%) gaining FFM than males (36%). Total plasma AA increased (P < 0.05) during BCT, with greater (P < 0.05) increases observed in females (17%) then in males (4%). Essential amino acids (EAA) and branched-chain amino acids (BCAA) were increased (P < 0.05) in females but did not change in males (sex-by-time interaction, P < 0.05). Independent of sex, changes in EAA (r = 0.34) and BCAA (r = 0.27) from baseline were associated with changes in FFM (P < 0.05); greater (P < 0.05) increases in AA concentrations were observed for those who gained FFM. Increases in FFM and plasma AA suggest that BCT elicits a more pronounced anabolic response in women compared to men, which may reflect sex-specific differences in the relative intensity of the combined training and physiological stimulus associated with BCT. PMID:23250145

Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

PubMed

Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

2015-11-01

The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

Dietary fat (virgin olive oil or sunflower oil) and physical training interactions on blood lipids in the rat.

PubMed

Quiles, José L; Huertas, Jesús R; Ochoa, Julio J; Battino, Maurizio; Mataix, José; Mañas, Mariano

2003-04-01

We investigated whether the intake of virgin olive oil or sunflower oil and performance of physical exercise (at different states) affect plasma levels of triacylglycerols, total cholesterol, and fatty acid profile in rats. The study was carried out with six groups of male rats subjected for 8 wk to a diet based on virgin olive oil (three groups) or sunflower oil (three groups) as dietary fat. One group for each diet acted as sedentary control; the other two groups ran in a treadmill for 8 wk at 65% of the maximum oxygen consumption. One group for each diet was killed 24 h after the last bout of exercise and the other was killed immediately after the exercise performance. Triacylglycerols, total cholesterol, and fatty acid profile were analyzed in plasma. Analysis of variance was used to test differences among groups. Animals fed on virgin olive oil had lower triacylglycerol and cholesterol values. Physical exercise reduced these parameters with both dietary treatments. Fatty acid profile showed higher monounsaturated fatty acid proportion in virgin olive fed oil animals and a higher omega-6 polyunsaturated fatty acid proportion in sunflower oil fed animals. Physical exercise reduced the levels of monounsaturated fatty acids with both diets and increased the proportions of omega-3 polyunsaturated fatty acids. Results from the present study supported the idea that physical exercise and the intake of virgin olive oil are very good ways of reducing plasma triacylglycerols and cholesterol, which is desirable in many pathologic situations. Concerning findings on fatty acid profile, we had results similar to those of other investigators regarding the effect of different sources of dietary fat on plasma. The most interesting results came from the effect of physical exercise, with significant increases in the levels of omega-3 polyunsaturated fatty acids, which may contribute to the antithrombotic state and lower production of proinflammatory prostanoids attributed to physical exercise.

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

Peden, D.B.; Swiersz, M.; Ohkubo, K.

Uric acid, an important scavenger of ozone, has been identified as the major low molecular weight antioxidant in baseline and cholinergically induced nasal secretions. The purpose of this study was to determine the specific tissue source of uric acid in airway secretions. The secretion of uric acid is increased by cholinergic stimulation and correlates closely with the secretion of lactoferrin (a nasal glandular protein), suggesting that submucosal glands are involved. Indeed, nasal turbinate tissue was found to contain uric acid. However, careful analysis of nasal turbinate tissue failed to reveal the presence of xanthine oxidase, the enzyme responsible for uricmore » acid synthesis. These data suggest that uric acid might be taken up secondarily by glands from plasma. This possibility was strengthened by the observation that lowering the plasma urate level with probenecid concomitantly lowered urate secretion. These findings are consistent with the hypotheses that the principal source of uric acid in nasal secretions is plasma and that uric acid is taken up, concentrated, and secreted by nasal glands.« less

Interaction of SNP in the CRP gene and plasma fatty acid profile in inflammatory pattern: A cross-sectional population-based study.

PubMed

Oki, Erica; Norde, Marina M; Carioca, Antônio A F; Ikeda, Renata E; Souza, José M P; Castro, Inar A; Marchioni, Dirce M L; Fisberg, Regina M; Rogero, Marcelo M

2016-01-01

To assess the interaction of three single nucleotide polymorphisms in the C-reactive protein (CRP) gene and plasma fatty acid (FA) levels in modulating inflammatory profile. A total of 262 subjects, aged >19 y and <60 y, participated in a cross-sectional, population-based study performed in Brazil. Three single nucleotide polymorphisms (rs1205, rs1417938, and rs2808630) spanning the CRP gene were genotyped. Eleven plasma inflammatory biomarkers and plasma FA profile were determined. Cluster analysis was performed to stratify individuals based on eleven inflammatory biomarkers into two groups: an inflammatory (INF) and a noninflammatory group. The INF cluster had higher age, waist circumference, systolic blood pressure, and diastolic blood pressure; higher levels of triacylglycerol, high-sensitivity CRP, tumor necrosis factor-α, interleukin (IL)-8, IL-6, IL-1β, IL-12, IL-10, soluble monocyte chemoattractant protein-1, soluble intercellular adhesion molecule-1, C16:0, polyunsaturated fatty acid, and omega (n)-6 polyunsaturated fatty acid; and greater C20:4n-6, C18:1/18:0, and C20:4/20:3 ratios than the noninflammatory group. Statistically significant gene-plasma C16:1n-7 interaction was detected for rs1417938 (P = 0.047). Those with a dominant homozygous rs2808630 had a lower risk of belonging to the INF group with the upper 50th percentile of C20:4n-6, n-3 highly unsaturated FA, and C20:4/20:3 ratio. Regarding rs1205, A allele carriers had lower risk of being in the INF group when C20:5n-3 and n-3 highly unsaturated FA levels were greater than the median. The INF group exhibited changes in metabolic parameters that predispose this group to chronic disease, where polymorphisms in the CRP gene modulated the risk of being in the INF group depending on individual plasma fatty acid and lipid profile. Copyright © 2016 Elsevier Inc. All rights reserved.

Associations Between Insulin Resistance, Free Fatty Acids, and Oocyte Quality in Polycystic Ovary Syndrome During In Vitro Fertilization

PubMed Central

Niu, Zhihong; Lin, Nan; Gu, Ruihuan; Sun, Yijuan

2014-01-01

Context: Both polycystic ovary syndrome (PCOS) and obesity are associated with specific reproductive health complications, including lower oocyte quality and clinical pregnancy rates in assisted conception cycles, which may be a result of metabolism-induced changes in the oocyte through the microenvironment of follicular fluid. Free fatty acids (FFAs) are important biomedical indicators of abnormal lipid metabolism and have pronounced effects on cells, leading to changes in metabolism, cell growth, and differentiation Objective: Our objective was to determine the effect of FFA metabolism in plasma and follicular fluid on oocyte quality in the women with PCOS undergoing in vitro fertilization. Design and Setting: Ninety-three women undergoing in vitro fertilization treatment, including 55 with PCOS and 38 age-matched controls, were recruited. PCOS patients were divided into obese and nonobese subgroups on the basis of their body mass index. Main Outcome Measures: Embryo quality was morphologically assessed, and serum sex hormone and insulin levels were measured. FFAs in plasma and follicular fluid were measured using gas chromatography-mass spectrometry. Results: PCOS was found to be associated with significantly higher LH/FSH, total T, free androgen index (FAI), and lower SHBG levels, independent of obesity(P < .05). Obese women with PCOS had a significantly higher total T level, FAI, fasting insulin, insulin resistance index as determined by homeostasis model assessment for insulin resistance, and lower SHBG levels than the nonobese women with PCOS (P < .05). The embryo fragmentation score was significantly positively correlated with the oleic acid concentration in all PCOS patients (r = 0.22, P = .04, for nonobese patients and r = 0.25, P = .03, for obese patients). Conclusions: Our findings clearly demonstrated that PCOS is associated with significantly higher FAI and insulin resistance levels and decreased plasma SHBG levels, independent of body mass index. Obese PCOS patients had higher palmitoleic acid and oleic acid levels in both the plasma and follicular fluid than did the control subject and nonobese PCOS patients. Our results indicated that developmental competence is associated with oleic and stearic acid concentrations, which may contribute to the poor pregnancy outcomes in patients with PCOS. PMID:24694334

Structured triglycerides containing caprylic (8:0) and oleic (18:1) fatty acids reduce blood cholesterol concentrations and aortic cholesterol accumulation in hamsters.

PubMed

Wilson, Thomas A; Kritchevsky, David; Kotyla, Timothy; Nicolosi, Robert J

2006-03-01

The effects of structured triglycerides containing one long chain fatty acid (oleic acid, C18:1) and one short chain saturated fatty acid (caprylic acid, 8:0) on lipidemia, liver and aortic cholesterol, and fecal neutral sterol excretion were investigated in male Golden Syrian hamsters fed a hypercholesterolemic regimen consisting of 89.9% commercial ration to which was added 10% coconut oil and 0.1% cholesterol (w/w). After 2 weeks on the HCD diet, the hamsters were bled, following an overnight fast (16 h) and placed into one of three dietary treatments of eight animals each based on similar plasma cholesterol levels. The hamsters either continued on the HCD diet or were placed on diets in which the coconut oil was replaced by one of two structured triglycerides, namely, 1(3),2-dicaproyl-3(1)-oleoylglycerol (OCC) or 1,3-dicaproyl-2-oleoylglycerol (COC) at 10% by weight. Plasma total cholesterol (TC) in hamsters fed the OCC and COC compared to the HCD were reduced 40% and 49%, respectively (P<0.05). Similarly, hamsters fed the OCC and COC diets reduced their plasma nonHDL cholesterol levels by 47% and 57%, respectively (P<0.05), compared to hamsters fed the HCD after 2 weeks of dietary treatment. Although hamsters fed the OCC (-26%) and COC (-32%) had significantly lower plasma HDL levels compared to HCD, (P<0.05), the plasma nonHDL/HDL cholesterol ratio was significantly lower (P<0.05) compared to the HCD for the OCC-fed (-27%) and the COC-fed (-38%) hamsters, respectively. Compared to the HCD group, aortic esterified cholesterol was 20% and 53% lower for the OCC and COC groups, respectively, with the latter reaching statistical significance, P<0.05. In conclusion, the hamsters fed the structured triglyceride oils had lower blood cholesterol levels and lower aortic accumulation of cholesterol compared to the control fed hamsters.

LC-MS/MS-based quantification of kynurenine metabolites, tryptophan, monoamines and neopterin in plasma, cerebrospinal fluid and brain.

PubMed

Fuertig, René; Ceci, Angelo; Camus, Sandrine M; Bezard, Erwan; Luippold, Andreas H; Hengerer, Bastian

2016-09-01

The kynurenine (KYN) pathway is implicated in diseases such as cancer, psychiatric, neurodegenerative and autoimmune disorders. Measurement of KYN metabolite levels will help elucidating the involvement of the KYN pathway in the disease pathology and inform drug development. Samples of plasma, cerebrospinal fluid or brain tissue were spiked with deuterated internal standards, processed and analyzed by LC-MS/MS; analytes were chromatographically separated by gradient elution on a C18 reversed phase analytical column without derivatization. We established an LC-MS/MS method to measure 11 molecules, namely tryptophan, KYN, 3-OH-KYN, 3-OH-anthranilic acid, quinolinic acid, picolinic acid, kynurenic acid, xanthurenic acid, serotonin, dopamine and neopterin within 5.5 min, with sufficient sensitivity to quantify these molecules in small sample volumes of plasma, cerebrospinal fluid and brain tissue.

Use of Folic Acid Supplements in Early Pregnancy in Relation to Maternal Plasma Levels in Week 18 of Pregnancy

PubMed Central

Roth, Christine; Monsen, Anne Lise B.; Reichborn-Kjennerud, Ted; Nilsen, Roy M.; Smith, George Davey; Stoltenberg, Camilla; Surén, Pål; Susser, Ezra; Ueland, Per Magne; Vollset, Stein Emil; Magnus, Per

2013-01-01

We compared plasma-folate at week 18 of gestation with self-reported use of supplements containing folic acid from before pregnancy to 17 weeks gestation. Birth cohorts typically measure plasma-folate in mid-gestation, but effects of folic acid supplementation are sometimes specific to the periconceptional period. The relationship between mid-gestation plasma-folate and periconceptional supplementation is not known. The sample comprised 2911 women from The Norwegian Mother and Child Cohort Study. For women reporting continuous supplementation from gestational week -4-17 (N=238), median plasma-folate was 15.72 at week 18 (in nmol/L). This was about threefold higher than the median plasma-folate of 5.67 for women reporting no supplementation from week -4-17 (N=844), but only slightly higher than the median plasma-folate of 13.34 for all women reporting supplementation in week 13-17 (N=1158). Reported supplementation before week 8 was not associated with plasma-folate at week 18, in an analysis that adjusted for continued supplementation after week 8. Overall we found a strong and coherent relationship between self-reported folic acid use and plasma-folate at week 18. We also found that plasma-folate at week 18 did not reflect self-reported supplementation before 8 weeks. For periconceptional supplementation per se, self-report data may offer a better measure. PMID:23065724

Evaluation of plasma antioxidant activity in rats given excess EGCg with reference to endogenous antioxidants concentrations and assay methods.

PubMed

Yokotani, Kaori; Umegaki, Keizo

2017-02-01

The contribution of (-)-epigallocatechin gallate (EGCg) intake to in vivo antioxidant activity is unclear, even with respect to plasma. In this study, we examined how administration of EGCg contributes to plasma antioxidant activity, relative to its concentration, endogenous antioxidants, and assay methods, namely oxygen radical absorbance capacity (ORAC) and ferric reducing/antioxidant power (FRAP). Administration of EGCg (500 mg/kg) to rats increased plasma EGCg (4μmol/L as free form) and ascorbic acid (1.7-fold), as well as ORAC (1.2-fold) and FRAP (3-fold) values. The increase in plasma ascorbic acid following EGCg administration was accompanied by its relocation from the adrenal glands and lymphocytes into plasma, and was related to the increase in FRAP. Plasma deproteinization and assays in plasma model solutions revealed that protein levels significantly contributed to ORAC values, where <3 μmol/L EGCg in the presence of protein exhibited minimal antioxidant activity, as measured by both FRAP and ORAC. As the concentration of plasma ascorbic acid was not influenced by deproteinization, differences in FRAP values with and without deproteinization were estimated to determine the contribution of enhanced ascorbic acid attributable to EGCg administration. These results will help to understand the points that should be considered when evaluating EGCg antioxidant activity in plasma.

Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis.

PubMed

de Almeida, I Tavares; Cortez-Pinto, H; Fidalgo, G; Rodrigues, D; Camilo, M E

2002-06-01

Non-alcoholic steatohepatitis (NASH), the association of steatosis with an inflammatory response, is a novel liver disease of unknown pathogenesis and prognosis. Triacylglycerols and their precursors, the fatty acids, are the likely candidates to accumulate in the hepatocyte. Disturbed fatty acid metabolism can be involved in the pathogenesis of NASH but there is no information concerning its plasma fatty acid profile. The aim of this study was to evaluate plasma total (esterified plus free) and free fatty acids concentrations to assess the association of NASH with plasma fatty acid accumulation. Overnight fasting blood samples from 22 biopsy-proven NASH patients and of 6 matched age healthy controls were studied. NASH patients had significantly higher concentration of total and free fatty acids than controls (P<0.05), higher total saturated and monounsaturated levels in both studied lipid fractions (P<0.05), mainly due to the increase of hexadecanoic, hexadecenoic and octadecenoic acids. Absolute polyunsaturated fatty acids (PUFA) concentrations were similar in both groups. The C20:4/C18:2 and the C18:1/C18:0 ratios as well as the peroxidability index were not significantly different. In overweight/obese patients NASH is associated with deranged fatty acid metabolism which may be involved in its pathogenesis and/or progression.

Amino Acid Derivatives as Palmitoylethanolamide Prodrugs: Synthesis, In Vitro Metabolism and In Vivo Plasma Profile in Rats

PubMed Central

Vacondio, Federica; Bassi, Michele; Silva, Claudia; Castelli, Riccardo; Carmi, Caterina; Scalvini, Laura; Lodola, Alessio; Vivo, Valentina; Flammini, Lisa; Barocelli, Elisabetta; Mor, Marco; Rivara, Silvia

2015-01-01

Palmitoylethanolamide (PEA) has antinflammatory and antinociceptive properties widely exploited in veterinary and human medicine, despite its poor pharmacokinetics. Looking for prodrugs that could progressively release PEA to maintain effective plasma concentrations, we prepared carbonates, esters and carbamates at the hydroxyl group of PEA. Chemical stability (pH 7.4) and stability in rat plasma and liver homogenate were evaluated by in vitro assays. Carbonates and carbamates resulted too labile and too resistant in plasma, respectively. Ester derivatives, prepared by conjugating PEA with various amino acids, allowed to modulate the kinetics of PEA release in plasma and stability in liver homogenate. L-Val-PEA, with suitable PEA release in plasma, and D-Val-PEA, with high resistance to hepatic degradation, were orally administered to rats and plasma levels of prodrugs and PEA were measured at different time points. Both prodrugs showed significant release of PEA, but provided lower plasma concentrations than those obtained with equimolar doses of PEA. Amino-acid esters of PEA are a promising class to develop prodrugs, even if they need further chemical optimization. PMID:26053855

Gas Chromatography/Mass Spectrometry-Based Metabolomic Profiling Reveals Alterations in Mouse Plasma and Liver in Response to Fava Beans.

PubMed

Xiao, Man; Du, Guankui; Zhong, Guobing; Yan, Dongjing; Zeng, Huazong; Cai, Wangwei

2016-01-01

Favism is a life-threatening hemolytic anemia resulting from the intake of fava beans by susceptible individuals with low erythrocytic glucose 6-phosphate dehydrogenase (G6PD) activity. However, little is known about the metabolomic changes in plasma and liver after the intake of fava beans in G6PD normal and deficient states. In this study, gas chromatography/mass spectrometry was used to analyze the plasma and liver metabolic alterations underlying the effects of fava beans in C3H- and G6PD-deficient (G6PDx) mice, and to find potential biomarkers and metabolic changes associated with favism. Our results showed that fava beans induced oxidative stress in both C3H and G6PDx mice. Significantly, metabolomic differences were observed in plasma and liver between the control and fava bean treated groups of both C3H and G6PDx mice. The levels of 7 and 21 metabolites in plasma showed significant differences between C3H-control (C3H-C)- and C3H fava beans-treated (C3H-FB) mice, and G6PDx-control (G6PDx-C)- and G6PDx fava beans-treated (G6PDx-FB) mice, respectively. Similarly, the levels of 7 and 25 metabolites in the liver showed significant differences between C3H and C3H-FB, and G6PDx and G6PDx-FB, respectively. The levels of oleic acid, linoleic acid, and creatinine were significantly increased in the plasma of both C3H-FB and G6PDx-FB mice. In the liver, more metabolic alterations were observed in G6PDx-FB mice than in C3H-FB mice, and were involved in a sugar, fatty acids, amino acids, cholesterol biosynthesis, the urea cycle, and the nucleotide metabolic pathway. These findings suggest that oleic acid, linoleic acid, and creatinine may be potential biomarkers of the response to fava beans in C3H and G6PDx mice and therefore that oleic acid and linoleic acid may be involved in oxidative stress induced by fava beans. This study demonstrates that G6PD activity in mice can affect their metabolic pathways in response to fava beans.

Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids.

PubMed

Gibson, R A; Neumann, M A; Lien, E L; Boyd, K A; Tu, W C

2013-01-01

The conversion of the plant-derived omega-3 (n-3) α-linolenic acid (ALA, 18:3n-3) to the long-chain eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) can be increased by ALA sufficient diets compared to ALA deficient diets. Diets containing ALA above an optimal level result in no further increase in DHA levels in animals and humans. The present study evaluates means of maximizing plasma DHA accumulation by systematically varying both linoleic acid (LA, 18:2n-6) and ALA dietary level. Weanling rats were fed one of 54 diets for three weeks. The diets varied in the percentage of energy (en%) of LA (0.07-17.1 en%) and ALA (0.02-12.1 en%) by manipulating both the fat content and the balance of vegetable oils. The peak of plasma phospholipid DHA (>8% total fatty acids) was attained as a result of feeding a narrow dietary range of 1-3 en% ALA and 1-2 en% LA but was suppressed to basal levels (∼2% total fatty acids) at dietary intakes of total polyunsaturated fatty acids (PUFA) above 3 en%. We conclude it is possible to enhance the DHA status of rats fed diets containing ALA as the only source of n-3 fatty acids but only when the level of dietary PUFA is low (<3 en%). Copyright © 2012 Elsevier Ltd. All rights reserved.

Polymorphisms in Genes Involved in Fatty Acid β-Oxidation Interact with Dietary Fat Intakes to Modulate the Plasma TG Response to a Fish Oil Supplementation

PubMed Central

Bouchard-Mercier, Annie; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2014-01-01

A large inter-individual variability in the plasma triglyceride (TG) response to an omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been observed. The objective was to examine gene-diet interaction effects on the plasma TG response after a fish oil supplementation, between single-nucleotide polymorphisms (SNPs) within genes involved in fatty acid β-oxidation and dietary fat intakes. Two hundred and eight (208) participants were recruited in the greater Quebec City area. The participants completed a six-week fish oil supplementation (5 g fish oil/day: 1.9–2.2 g EPA and 1.1 g DHA). Dietary fat intakes were measured using three-day food records. SNPs within RXRA, CPT1A, ACADVL, ACAA2, ABCD2, ACOX1 and ACAA1 genes were genotyped using TAQMAN methodology. Gene-diet interaction effects on the plasma TG response were observed for SNPs within RXRA (rs11185660, rs10881576 and rs12339187) and ACOX1 (rs17583163) genes. For rs11185660, fold changes in RXRA gene expression levels were different depending on SFA intakes for homozygotes T/T. Gene-diet interaction effects of SNPs within genes involved in fatty acid β-oxidation and dietary fat intakes may be important in understanding the inter-individual variability in plasma TG levels and in the plasma TG response to a fish oil supplementation. PMID:24647074

Effects of debrisoquin and haloperidol on plasma homovanillic acid concentration in schizophrenic patients.

PubMed

Davidson, M; Losonczy, M F; Mohs, R C; Lesser, J C; Powchik, P; Freed, L B; Davis, B M; Mykytyn, V V; Davis, K L

1987-12-01

Plasma levels of the dopamine metabolite homovanillic acid (pHVA) may potentially reflect upon central dopamine activity. This study examines the effects of debrisoquin, haloperidol, and the two drugs combined on pHVA concentrations of schizophrenic patients. Debrisoquin is a drug that suppresses the peripheral formation of homovanillic acid without affecting the central formation. Acute haloperidol administration consistently increased pHVA concentrations in patients pretreated or not pretreated with debrisoquin, suggesting that this increment reflects haloperidol's central and not peripheral effects.

Plasma long-chain omega-3 polyunsaturated fatty acids and macular pigment in subjects with family history of age-related macular degeneration: the Limpia Study.

PubMed

Merle, Bénédicte M J; Buaud, Benjamin; Korobelnik, Jean-François; Bron, Alain; Delyfer, Marie-Noëlle; Rougier, Marie-Bénédicte; Savel, Hélène; Vaysse, Carole; Creuzot-Garcher, Catherine; Delcourt, Cécile

2017-12-01

In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (β = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion.

PubMed

Quartu, Marina; Serra, Maria P; Boi, Marianna; Pillolla, Giuliano; Melis, Tiziana; Poddighe, Laura; Del Fiacco, Marina; Falconieri, Danilo; Carta, Gianfranca; Murru, Elisabetta; Cordeddu, Lina; Piras, Antonio; Collu, Maria; Banni, Sebastiano

2012-01-12

Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury.

Effect of acute administration of Pistacia lentiscus L. essential oil on rat cerebral cortex following transient bilateral common carotid artery occlusion

PubMed Central

2012-01-01

Background Ischemia/reperfusion leads to inflammation and oxidative stress which damages membrane highly polyunsaturated fatty acids (HPUFAs) and eventually induces neuronal death. This study evaluates the effect of the administration of Pistacia lentiscus L. essential oil (E.O.), a mixture of terpenes and sesquiterpenes, on modifications of fatty acid profile and endocannabinoid (eCB) congener concentrations induced by transient bilateral common carotid artery occlusion (BCCAO) in the rat frontal cortex and plasma. Methods Adult Wistar rats underwent BCCAO for 20 min followed by 30 min reperfusion (BCCAO/R). 6 hours before surgery, rats, randomly assigned to four groups, were gavaged either with E.O. (200 mg/0.45 ml of sunflower oil as vehicle) or with the vehicle alone. Results BCCAO/R triggered in frontal cortex a decrease of docosahexaenoic acid (DHA), the membrane highly polyunsaturated fatty acid most susceptible to oxidation. Pre-treatment with E.O. prevented this change and led further to decreased levels of the enzyme cyclooxygenase-2 (COX-2), as assessed by Western Blot. In plasma, only after BCCAO/R, E.O. administration increased both the ratio of DHA-to-its precursor, eicosapentaenoic acid (EPA), and levels of palmytoylethanolamide (PEA) and oleoylethanolamide (OEA). Conclusions Acute treatment with E.O. before BCCAO/R elicits changes both in the frontal cortex, where the BCCAO/R-induced decrease of DHA is apparently prevented and COX-2 expression decreases, and in plasma, where PEA and OEA levels and DHA biosynthesis increase. It is suggested that the increase of PEA and OEA plasma levels may induce DHA biosynthesis via peroxisome proliferator-activated receptor (PPAR) alpha activation, protecting brain tissue from ischemia/reperfusion injury. PMID:22239952

Plasma alpha-1-acid glycoprotein as a potential predictive biomarker for non-haematological adverse events of docetaxel in breast cancer patients.

PubMed

Jabir, Rafid Salim; Ho, Gwo Fuang; Annuar, Muhammad Azrif Bin Ahmad; Stanslas, Johnson

2018-03-01

Rash and oral mucositis are major non-haematological adverse events (AEs) of docetaxel, in addition to fatigue, nausea, vomiting and diarrhoea, which restrict the use of the drug in cancer therapy. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel has extensive binding (>98%) to plasma proteins such as AAG, lipoproteins and albumin. To study the association between plasma AAG level and non-haematological AEs of docetaxel in Malaysian breast cancer patients of three major ethnic groups (Malays, Chinese and Indians). One hundred and twenty Malaysian breast cancer patients receiving docetaxel as single agent chemotherapy were investigated for AAG plasma level using enzyme-linked immunosorbent assay technique. Toxicity assessment was determined using Common Terminology Criteria of Adverse Events v4.0. The association between AAG and toxicity were then established. There was interethnic variation of plasma AAG level; it was 182 ± 85 mg/dl in Chinese, 237 ± 94 mg/dl in Malays and 240 ± 83 mg/dl in Indians. It was found that low plasma levels of AAG were significantly associated with oral mucositis and rash. This study proposes plasma AAG as a potential predictive biomarker of docetaxel non-haematological AEs namely oral mucositis and rash.

Omega-3 fatty acid enriched chevon (goat meat) lowers plasma cholesterol levels and alters gene expressions in rats.

PubMed

Ebrahimi, Mahdi; Rajion, Mohamed Ali; Meng, Goh Yong; Soleimani Farjam, Abdoreza

2014-01-01

In this study, control chevon (goat meat) and omega-3 fatty acid enriched chevon were obtained from goats fed a 50% oil palm frond diet and commercial goat concentrate for 100 days, respectively. Goats fed the 50% oil palm frond diet contained high amounts of α-linolenic acid (ALA) in their meat compared to goats fed the control diet. The chevon was then used to prepare two types of pellets (control or enriched chevon) that were then fed to twenty-male-four-month-old Sprague-Dawley rats (n = 10 in each group) for 12 weeks to evaluate their effects on plasma cholesterol levels, tissue fatty acids, and gene expression. There was a significant increase in ALA and docosahexaenoic acid (DHA) in the muscle tissues and liver of the rats fed the enriched chevon compared with the control group. Plasma cholesterol also decreased (P < 0.05) in rats fed the enriched chevon compared to the control group. The rat pellets containing enriched chevon significantly upregulated the key transcription factor PPAR-γ and downregulated SREBP-1c expression relative to the control group. The results showed that the omega-3 fatty acid enriched chevon increased the omega-3 fatty acids in the rat tissues and altered PPAR-γ and SREBP-1c genes expression.

HETEROGENEITY IN PLASMA HOMOVANILLIC ACID LEVELS IN SCHIZOPHRENIFORM DISORDER

PubMed Central

Pradhan, N.; Harihar, C.; Das, P.; Andrade, C.

1992-01-01

Plasma homovanillic acid (pHVA) levels were estimated in 20 cases of schizophreniform disorder, 14 cases of schizophrenia ‘on medication’ and 17 cases of schizophrenia ‘off medication’. A bimodal distribution of pHVA was seen in schizophreniform disorder subjects, suggesting heterogenous groups in terms of dopaminergic function. No significant difference in the pHVA values was seen in the 3 groups, nor was there a relationship between the severity of the illness and the pHVA values; these results suggest plasticity of the dopaminergic system to neuroleptics. PMID:21776112

Heterogeneity in plasma homovanillic Acid levels in schizophreniform disorder.

PubMed

Pradhan, N; Harihar, C; Das, P; Andrade, C

1992-04-01

Plasma homovanillic acid (pHVA) levels were estimated in 20 cases of schizophreniform disorder, 14 cases of schizophrenia 'on medication' and 17 cases of schizophrenia 'off medication'. A bimodal distribution of pHVA was seen in schizophreniform disorder subjects, suggesting heterogenous groups in terms of dopaminergic function. No significant difference in the pHVA values was seen in the 3 groups, nor was there a relationship between the severity of the illness and the pHVA values; these results suggest plasticity of the dopaminergic system to neuroleptics.

Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats.

PubMed

Hwang, Jinah; Chang, Yun-Hee; Park, Jung Hwa; Kim, Soo Yeon; Chung, Haeyon; Shim, Eugene; Hwang, Hye Jin

2011-10-20

Dietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO), olive oil (OO), and beef tallow (BT) on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity. Male Sprague-Dawley rats were fed 15% (wt/wt) CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg), samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity. Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets. Dietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity.

Nutritional Regulation of Bile Acid Metabolism Is Associated with Improved Pathological Characteristics of the Metabolic Syndrome*

PubMed Central

Liaset, Bjørn; Hao, Qin; Jørgensen, Henry; Hallenborg, Philip; Du, Zhen-Yu; Ma, Tao; Marschall, Hanns-Ulrich; Kruhøffer, Mogens; Li, Ruiqiang; Li, Qibin; Yde, Christian Clement; Criales, Gabriel; Bertram, Hanne C.; Mellgren, Gunnar; Øfjord, Erik Snorre; Lock, Erik-Jan; Espe, Marit; Frøyland, Livar; Madsen, Lise; Kristiansen, Karsten

2011-01-01

Bile acids (BAs) are powerful regulators of metabolism, and mice treated orally with cholic acid are protected from diet-induced obesity, hepatic lipid accumulation, and increased plasma triacylglycerol (TAG) and glucose levels. Here, we show that plasma BA concentration in rats was elevated by exchanging the dietary protein source from casein to salmon protein hydrolysate (SPH). Importantly, the SPH-treated rats were resistant to diet-induced obesity. SPH-treated rats had reduced fed state plasma glucose and TAG levels and lower TAG in liver. The elevated plasma BA concentration was associated with induction of genes involved in energy metabolism and uncoupling, Dio2, Pgc-1α, and Ucp1, in interscapular brown adipose tissue. Interestingly, the same transcriptional pattern was found in white adipose tissue depots of both abdominal and subcutaneous origin. Accordingly, rats fed SPH-based diet exhibited increased whole body energy expenditure and heat dissipation. In skeletal muscle, expressions of the peroxisome proliferator-activated receptor β/δ target genes (Cpt-1b, Angptl4, Adrp, and Ucp3) were induced. Pharmacological removal of BAs by inclusion of 0.5 weight % cholestyramine to the high fat SPH diet attenuated the reduction in abdominal obesity, the reduction in liver TAG, and the decrease in nonfasted plasma TAG and glucose levels. Induction of Ucp3 gene expression in muscle by SPH treatment was completely abolished by cholestyramine inclusion. Taken together, our data provide evidence that bile acid metabolism can be modulated by diet and that such modulation may prevent/ameliorate the characteristic features of the metabolic syndrome. PMID:21680746

Plasma debrisoquin levels in the assessment of reduction of plasma homovanillic acid. The debrisoquin method.

PubMed

Riddle, M A; Jatlow, P I; Anderson, G M; Cho, S C; Hardin, M T; Cohen, D J; Leckman, J F

1989-06-01

Plasma concentrations of unconjugated homovanillic acid (pHVA) reflect both central nervous system (CNS) and peripheral dopamine metabolism. Debrisoquin sulfate (DBQ) blocks peripheral, but not CNS, production of HVA from dopamine. Administration of DBQ has been used to decrease the proportion of peripherally produced HVA in pHVA measurements, making such measurements more reflective of CNS turnover of dopamine. We studied the relationships between DBQ dose, plasma DBQ (pDBQ) levels, and changes in pHVA in a group of 21 subjects (9 normal controls and 12 with Tourette's syndrome). DBQ dose was moderately correlated with pDBQ levels (r = 0.63, p = 0.002). Subjects (n = 8) with mean pDBQ levels above 60 ng/ml had a 48% to 66% decrease in mean pHVA levels; this may reflect nearly complete inhibition of peripheral HVA production. Subjects (n = 13) with mean pDBQ levels below 55 ng/ml had decreases in pHVA levels from 10% to 58%. No debrisoquin was detected in cerebrospinal fluid samples. These data suggest that pDBQ levels above 60 ng/ml are sufficient to assure substantial inhibition of peripheral HVA production and that monitoring pDBQ levels may be useful when employing this method for studying CNS metabolism.

Effect of Starvation on the Turnover and Metabolic Response to Leucine

PubMed Central

Sherwin, Robert S.

1978-01-01

l-Leucine was administered as a primed continuous 3-4-h infusion in nonobese and obese subjects in the postabsorptive state and for 12 h in obese subjects after a 3-day and 4-wk fast. In nonobese and obese subjects studied in the post-absorptive state, the leucine infusion resulted in a 150-200% rise in plasma leucine above preinfusion levels, a small decrease in plasma glucose, and unchanged levels of plasma insulin and glucagon and blood ketones. Plasma isoleucine (60-70%) and valine (35-40%) declined to a greater extent than other amino acids (P < 0.001). After 3 days and 4 wk of fasting, equimolar infusions of leucine resulted in two- to threefold greater increments in plasma leucine as compared to post-absorptive subjects, a 30-40% decline in other plasma amino acids, and a 25-30% decrease in negative nitrogen balance. Urinary excretion of 3-methylhistidine was however, unchanged. Plasma glucose which declined in 3-day fasted subjects after leucine administration, surprisingly rose by 20 mg/100 ml after 4 wk of fasting. The rise in blood glucose occurred in the absence of changes in plasma glucagon and insulin and in the face of a 15% decline in endogenous glucose production (as measured by infusion of [3-3H]glucose). On the other hand, fractional glucose utilization fell by 30% (P < 0.001), thereby accounting for hyperglycemia. The estimated metabolic clearance rate of leucine fell by 48% after 3 days of fasting whereas the plasma delivery rate of leucine was unchanged, thereby accounting for a 40% rise in plasma leucine during early starvation. After a 4-wk fast, the estimated metabolic clearance rate of leucine declined further to 59% below base line. Plasma leucine nevertheless fell to postabsorptive levels as the plasma delivery rate of leucine decreased 65% below postabsorptive values. Conclusions: (a) Infusion of exogenous leucine in prolonged fasting results in a decline in plasma levels of other amino acids, improvement in nitrogen balance and unchanged excretion of 3-methylhistidine, thus suggesting stimulation of muscle protein synthesis, (b) leucine infusion also reduces glucose production and to an even greater extent, glucose consumption, thereby raising blood glucose concentration; and (c) the rise in plasma leucine in early starvation results primarily from a decrease in leucine clearance which drops progressively during starvation. PMID:659610

Evolution of plasma homovanillic acid (HVA) levels during treatment in schizo-affective disorder.

PubMed

Galinowski, A; Castelnau, C; Spreux-Varoquaux, O; Bourdel, M C; Olie, J P; Loo, H; Poirier, M F

2000-11-01

1. Plasma Homovanillic Acid (p HVA) levels were measured by HPLC (high performance liquid chromatography) in 5 schizo-affective depressed patients receiving a standardized treatment. (lithium, chlorpromazine and clomipramine) during 4 weeks. 2. Four patients were pretreated, without a washout period. 3. No significant difference was observed between patients and normal controls at baseline. Under treatment, pHVA levels increased (p<0.02) with clinical improvement (MADRS and PANSS scores). 4. Although effects of medications prior to the study period were not controlled, these findings suggest that depressed schizo-affective patients may have normal pHVA levels that increase with clinical improvement, unlike schizophrenic patients whose increased pHVA concentrations decline with neuroleptic treatment.

Pharmacokinetics of aniracetam and its metabolites in rats.

PubMed

Ogiso, T; Iwaki, M; Tanino, T; Ikeda, K; Paku, T; Horibe, Y; Suzuki, H

1998-05-01

The pharmacokinetics of aniracetam (AP), a new cognitive performance enhancer, and its main metabolites was investigated after intravenous (iv) and oral administrations to rat. The plasma levels of AP, 4-p-anisamidobutyric acid (ABA), and p-anisic acid (AA) were determined simultaneously by the HPLC method. The plasma concentrations of the parent drug and ABA quickly declined in a biexponential manner, with rapid terminal decay and a small mean residence time. However, AA yielded nonlinearly high levels at the initial times and the plasma concentrations of 2-pyrrolidinone (PD) were sustained over a relatively long time. When AA was administered intravenously, nonlinearity of the plasma concentrations was also found at higher doses. To describe the time course of the plasma levels of AP and its metabolites after iv administration, a pharmacokinetic model with seven compartments was applied, which included 10 first-order rate constants and one Michaelis-Menten constant. An approximate fit was obtained between the observed and calculated curves based on the model, except for the plasma concentrations of ABA. The plasma concentration-time profiles of AP and its metabolites following oral administration of AP (50 and 100 mg/kg) were similar to those after iv dosing, with the exception of PD, which showed much lower plasma levels than those after iv administration. Elimination of AP and ABA was rapid after oral dosing, and the bioavailability of AP was extremely small (11.4 and 8.6%). As a result, AP was largely metabolized to ABA, AA, and PD in rat.

Activity of the sympathoadrenal system in cosmonauts during 25-day space flight on station Mir

NASA Astrophysics Data System (ADS)

Kvetňanský, R.; Noskov, V. B.; Blazicek, P.; Gharib, C.; Popova, I. A.; Gauquelin, G.; Macho, L.; Guell, A.; Grigoriev, A. I.

The activity of the sympathoadrenal system in cosmonauts was studied by measuring plasma and urinary catecholamines and their metabolites and conjugates. The appliance Plasma 02 was used for collecting, processing, and storing blood and urine samples from the cosmonauts during the course of a 25-day flight on board the station Mir. Plasma and urine concentrations of adrenaline (A), noradrenaline (NA), and dopamine (DA) as well as urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA), and plasma levels of catecholamine sulphates were determined before, during and after the space flight. Plasma NA levels were slightly elevated on day 9 and plasma A on day 20, whereas plasma DA levels were unchanged. However, most of the changes were within the normal range of control values. Sulphates of plasma catecholamines did not change during flight but they were significantly elevated after landing. Urinary levels of A, NA, DA, VMA, and HVA were comparable with preflight values but were elevated at the different intervals studied after landing. The results obtained suggest that in the short period of about 9 days of the cosmonaut's stay in space the sympathoadrenal system was slightly activated indicating a mild stressful influence of the initial period of flight. This short-term space flight compared to long-term flight did not as markedly activate the sympathoadrenal system during the process of re-adaptation to Earth's gravity after landing. Our data suggest that weightlessness is not a stressful factor activating the sympathoadrenal system but it sensitizes the responsiveness of this system during the re-adaptation period after space flight.

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

Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults.

PubMed

Stark, Ken D; Van Elswyk, Mary E; Higgins, M Roberta; Weatherford, Charli A; Salem, Norman

2016-07-01

Studies reporting blood levels of the omega-3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were systematically identified in order to create a global map identifying countries and regions with different blood levels. Included studies were those of healthy adults, published in 1980 or later. A total of 298 studies met all inclusion criteria. Studies reported fatty acids in various blood fractions including plasma total lipids (33%), plasma phospholipid (32%), erythrocytes (32%) and whole blood (3.0%). Fatty acid data from each blood fraction were converted to relative weight percentages (wt.%) and then assigned to one of four discrete ranges (high, moderate, low, very low) corresponding to wt.% EPA+DHA in erythrocyte equivalents. Regions with high EPA+DHA blood levels (>8%) included the Sea of Japan, Scandinavia, and areas with indigenous populations or populations not fully adapted to Westernized food habits. Very low blood levels (≤4%) were observed in North America, Central and South America, Europe, the Middle East, Southeast Asia, and Africa. The present review reveals considerable variability in blood levels of EPA+DHA and the very low to low range of blood EPA+DHA for most of the world may increase global risk for chronic disease. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians.

PubMed

Gälman, Cecilia; Miquel, Juan Francisco; Pérez, Rosa Maria; Einarsson, Curt; Ståhle, Lars; Marshall, Guillermo; Nervi, Flavio; Rudling, Mats

2004-03-01

Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P < 0.006). As compared with Hispanic women without gallstones, plasma 7 alpha-hydroxy-4-cholesten-3-one levels were increased by > or =100% (P < 0.002) in Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.

A Salmon Protein Hydrolysate Exerts Lipid-Independent Anti-Atherosclerotic Activity in ApoE-Deficient Mice

PubMed Central

Busnelli, Marco; Bjørndal, Bodil; Holm, Sverre; Brattelid, Trond; Manzini, Stefano; Ganzetti, Giulia S.; Dellera, Federica; Halvorsen, Bente; Aukrust, Pål; Sirtori, Cesare R.; Nordrehaug, Jan E.; Skorve, Jon; Berge, Rolf K.; Chiesa, Giulia

2014-01-01

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E−/− mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE−/− mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20∶4n-6) and oleic acid (C18∶1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG) were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT)-activity. These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE−/− mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids. PMID:24840793

Effect of low-pressure plasma treatment on the color and oxidative stability of raw pork during refrigerated storage.

PubMed

Ulbin-Figlewicz, Natalia; Jarmoluk, Andrzej

2016-06-01

The effect of low-pressure plasma on quality attributes of meat is an important aspect, which must be considered before application in food. The aim of this study was to determine the color, fatty acid composition, lipid oxidation expressed as thiobarbituric acid reactive substances and total antioxidant capacity of raw pork samples exposed to helium low-pressure plasma treatment (20 kPa) for 0, 2, 5, and 10 min during the storage period. The thiobarbituric acid reactive substance concentrations of all plasma-treated samples during storage were in the range from 0.26 to 0.61 mg malondialdehyde/kg. Exposure time caused significant changes only in total color difference, hue angle, and chroma after 10 min of treatment. Ferric reducing ability of plasma values of meat samples decreased from 1.93 to 1.40 mmol Trolox Eq/kg after 14 days of storage. The storage period significantly affected proportion of polyunsaturated fatty acids, with an increase about 3% after 14 days of refrigeration storage while the content of saturated fatty acids was at the same level. Helium low-pressure plasma does not induce oxidative processes. Application of this decontamination technique while maintaining product quality is possible in food industry. © The Author(s) 2015.

Effects of dietary fats (fish, olive and high-oleic-acid sunflower oils) on lipid composition and antioxidant enzymes in rat liver.

PubMed

Ruiz-Gutiérrez, V; Pérez-Espinosa, A; Vázquez, C M; Santa-María, C

1999-09-01

The effects of two oleic-acid-rich diets (containing olive oil, OO, and high-oleic-acid sunflower oil, HOSO) on plasma and liver lipid composition detoxification enzyme activities, were compared with those of a fish-oil (FO) diet and a control diet. Compared with the control diet, plasma and hepatic total triacylglycerol concentrations were increased in the animals fed on the HOSO and OO diets and decreased in those fed on the FO diet. The animals fed on FO showed the highest level of cholesterol in the liver and had lower plasma cholesterol concentrations when compared with those fed on the two oleic-acid-rich diets. In comparison with the animals fed on the diets enriched in oleic acid, the FO group showed higher hepatic levels of polyunsaturated fatty acids of the n-3 series and lower levels of fatty acids of the n-6 series. Livers of FO-fed rats, compared with those of OO- and HOSO-fed rats showed: (1) significantly higher activities of catalase (EC 1.11.1.6) glutathione peroxidase (EC 1.11.1.9) and Cu/Zn superoxide dismutase (EC 1.15.1.1); (2) no differences in the NADPH-cytochrome c reductase (EC 1.6.99.3) activity. The HOSO diet had a similar effect on liver antioxidant enzyme activities as the OO diet. In conclusion, it appears that changes in the liver fatty acid composition due mainly to n-3 lipids may enhance the efficiency of the antioxidant defence system. The two monounsaturated fatty acids oils studied (OO and HOSO), with the same high content of oleic acid but different contents of natural antioxidants, had similar effects on the antioxidant enzyme activities measured.

Low gastric acid and high plasma gastrin in high-anxiety Wistar Kyoto rats.

PubMed

Florentzson, Malin; Svensson, Karin; Astin-Nielsen, Maria; Andersson, Kjell; Håkanson, Rolf; Lindstrom, Erik

2009-01-01

Wistar Kyoto (WKY) rats are more susceptible to stress-evoked ulcerations than Sprague-Dawley (SPD) rats. We have already demonstrated that gastrin cells are more active and ghrelin cells less active in WKY rats than in SPD rats. The purpose of this study was to compare endocrine cell activity and gastric acid output in WKY and SPD rats. Gastric acid output was determined in conscious rats with gastric fistula. Plasma gastrin and ghrelin levels were measured after an overnight fast. Acid secretagogues (gastrin, histamine and carbachol) were given by continuous subcutaneous infusion. The volume of gastric juice, and the acidity and acid output were all significantly lower (p <0.05) in fasted WKY rats than in fasted SPD rats. Gastrin evoked a 4-fold (p <0.01) and 3-fold (p <0.05) increase in gastric acid output in SPD rats and WKY rats, respectively. Histamine raised the acid output 1.6-fold in SPD rats (p=0.06) and 3-fold in WKY rats (p <0.05), while carbachol failed to affect the acid output (weak increase, p >0.05). Fasting plasma ghrelin levels were 2-fold higher in SPD rats than in WKY rats (p <0.01) while fasting gastrin levels were 10-fold higher in WKY rats than in SPD rats (p <0.05). Neither the parietal-cell density nor the oxyntic mucosal thickness differed between the two strains. The results of the present study suggest that a high gastrin cell activity in WKY rats is secondary to a low gastric acidity. Whether the high gastrin cell activity is linked to susceptibility to stress ulcer in WKY rats warrants further investigation.

Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

PubMed Central

St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH

2002-01-01

Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent. PMID:11825344

Different effects of fenofibrate on metabolic and cardiovascular risk factors in mixed dyslipidemic women with normal thyroid function and subclinical hypothyroidism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Szkrobka, Witold; Okopien, Bogusław

2014-12-01

Subclinical hypothyroidism is suggested to increase cardiovascular risk. No previous study compared the effect of any fibrate on plasma levels of lipids and other cardiovascular risk factors in patients with different thyroid function status. The study included three age-, weight- and lipid-matched groups of women with mixed dyslipidemia in different thyroid function status: patients with untreated subclinical hypothyroidism (group 1, n = 18), women with treated hypothyroidism (group 2, n = 15), and subjects without thyroid disorders (group 3, n = 19). Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. Despite similar plasma lipid levels, mixed dyslipidemic patients with untreated hypothyroidism had decreased insulin sensitivity, as well as higher circulating levels of uric acid, hsCRP, homocysteine, and fibrinogen in comparison with the other groups. The effect of fenofibrate on plasma lipids and, with the exception of homocysteine, on circulating levels of all investigated risk factors was stronger in patients from groups 2 and 3 than in patients from group 1. The obtained results indicate that the effect of fenofibrate on plasma lipids and circulating levels of cardiovascular risk factors is partially related to thyroid function. They also suggest that to improve the strength of fibrate action in dyslipidemic patients with subclinical hypothyroidism, they should be administered together with L-thyroxine. © 2014 John Wiley & Sons Ltd.

Variation in plasma amino acid concentrations during a cycling competition.

PubMed

Medelli, J; Lounana, J; Hill, D

2003-06-01

The variations in plasma concentrations of 24 amino acids (AAs) were measured, taking into account modifications in plasma volume, in 7 male subjects, professional cyclists, during the first 2 stages (EI and EII) of the competition "4 Days of Dunkirk 1999". Blood samples were taken before the start and at the end of each stage. At the end of EI a significant reduction (p<0.02) in alpha-aminobutyric acid was observed (-38%) and a significant increase (Wilcoxon 0.01

The influence of hydroxyurea on oxidative stress in sickle cell anemia

PubMed Central

Torres, Lidiane de Souza; da Silva, Danilo Grünig Humberto; Belini Junior, Edis; de Almeida, Eduardo Alves; Lobo, Clarisse Lopes de Castro; Cançado, Rodolfo Delfini; Ruiz, Milton Artur; Bonini-Domingos, Claudia Regina

2012-01-01

Objective The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. Methods Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. Results Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). Conclusion Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals. PMID:23323065

Effects of two whole-grain barley varieties on caecal SCFA, gut microbiota and plasma inflammatory markers in rats consuming low- and high-fat diets.

PubMed

Zhong, Yadong; Marungruang, Nittaya; Fåk, Frida; Nyman, Margareta

2015-05-28

Mixed-linkage β-glucans are fermented by the colon microbiota that give rise to SCFA. Propionic and butyric acids have been found to play an important role in colonic health, as well as they may have extraintestinal metabolic effects. The aim of the present study was to investigate how two whole-grain barley varieties differing in dietary fibre and β-glucan content affected caecal SCFA, gut microbiota and some plasma inflammatory markers in rats consuming low-fat (LF) or high-fat (HF) diets. Barley increased the caecal pool of SCFA in rats fed the LF and HF diets compared with those fed the control diet, and the effect was generally dependent on fibre content, an exception was butyric acid in the LF setting. Furthermore, whole-grain barley reduced plasma lipopolysaccharide-binding protein and monocyte chemoattractant protein-1, increased the caecal abundance of Lactobacillus and decreased the Bacteroides fragilis group, but increased the number of Bifidobacterium only when dietary fat was consumed at a low level. Fat content influenced the effects of barley: rats fed the HF diets had a higher caecal pool of acetic and propionic acids, higher concentrations of amino acids and higher amounts of lipids in the portal plasma and liver than rats fed the LF diets; however, less amounts of butyric acid were generally formed. Interestingly, there was an increase in the caecal abundance of Akkermansia and the caecal pool of succinic acid, and a decrease in the proportion of Bifidobacterium and the Clostridium leptum group. In summary, whole-grain barley decreased HF diet-induced inflammation, which was possibly related to the formation of SCFA and changes in microbiota composition. High β-glucan content in the diet was associated with reduced plasma cholesterol levels.

The effects of arachidonic acid on the endocrine and osmoregulatory response of tilapia (Oreochromis mossambicus) acclimated to seawater and subjected to confinement stress.

PubMed

Van Anholt, R D; Spanings, F A T; Nixon, O; Wendelaar Bonga, S E; Koven, W M

2012-06-01

In previous studies in freshwater tilapia (Oreochromis mossambicus), dietary supplementation with arachidonic acid (ArA; 20:4n - 6) had considerable, opposing effects on the main ion-transporting enzyme Na(+)/K(+)-ATPase in gills and kidneys and changed the release of osmoregulatory hormones, such as cortisol. The present study was performed to assess the influence of dietary ArA on (1) the osmoregulatory capacity of tilapia acclimated to seawater (SW) (34‰) and (2) the osmoregulatory imbalance associated with acute stress. The increased ambient salinity was associated with significant alterations in the tissue fatty acid composition, particularly the n - 6 polyunsaturated fatty acids (PUFAs). Tissue levels of ArA were further increased as a result of dietary supplementation, whereas docosahexaenoic acid (DHA, 22:6n - 3) and eicosapentaenoic acid (EPA, 20:5n - 3) decreased in gills and kidneys. Basal plasma cortisol as well as lactate levels were elevated in the ArA-supplemented SW-acclimated tilapia compared with the control group. The 5 min of confinement (transient stress) increased plasma cortisol, glucose, and lactate levels with significantly higher levels in ArA-supplemented tilapia. Confinement was also associated with significantly elevated plasma osmolality, sodium, chloride, and potassium levels. ArA-supplemented tilapia showed markedly lower ionic disturbances after confinement, suggesting that dietary ArA can attenuate the hydromineral imbalance associated with acute stress. These results emphasize the involvement of ArA and/or its metabolites in the endocrine and osmoregulatory processes and the response to confinement stress.

Omega-3 Fatty Acid Deficiency Augments Risperidone-Induced Hepatic Steatosis in Rats: Positive Association with Stearoyl-CoA Desaturase

PubMed Central

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

2012-01-01

Psychiatric patients frequently exhibit long-chain n-3 (LCn-3) fatty acid deficits and elevated triglyceride (TAG) production following chronic exposure to second generation antipsychotics (SGA). Emerging evidence suggests that SGAs and LCn-3 fatty acids have opposing effects on stearoyl-CoA desaturase-1 (SCD1), which plays a pivotal role in TAG biosynthesis. Here we evaluated whether low LCn-3 fatty acid status would augment elevations in rat liver and plasma TAG concentrations following chronic treatment with the SGA risperidone (RSP), and evaluated relationships with hepatic SCD1 expression and activity indices. In rats maintained on the n-3 fatty acid-fortified (control) diet, chronic RSP treatment significantly increased liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios), and significantly increased liver, but not plasma, TAG concentrations. Rats maintained on the n-3 deficient diet exhibited significantly lower liver and erythrocyte LCn-3 fatty acid levels, and associated elevations in LCn-6/LCn-3 ratio. In n-3 deficient rats, RSP-induced elevations in liver SCD1 mRNA and activity indices (18:1/18:0 and 16:1/16:0 ratios) and liver and plasma TAG concentrations were significantly greater than those observed in RSP-treated controls. Plasma glucose levels were not altered by diet or RSP, and body weight was lower in RSP- and VEH-treated n-3 deficient rats. These preclinical data support the hypothesis that low n-3 fatty acid status exacerbates RSP-induced hepatic steatosis by augmenting SCD1 expression and activity. PMID:22750665

Levels of cytokines in broncho-alveolar lavage fluid, but not in plasma, are associated with levels of markers of lipid peroxidation in breath of ventilated ICU patients.

PubMed

Boshuizen, Margit; Leopold, Jan Hendrik; Zakharkina, Tetyana; Knobel, Hugo H; Weda, Hans; Nijsen, Tamara M E; Vink, Teunis J; Sterk, Peter J; Schultz, Marcus J; Bos, Lieuwe D J

2015-09-03

Alkanes and alkenes in the breath are produced through fatty acid peroxidation, which is initialized by reactive oxygen species. Inflammation is an important cause and effect of reactive oxygen species. We aimed to evaluate the association between fatty acid peroxidation products and inflammation of the alveolar and systemic compartment in ventilated intensive care unit (ICU) patients.Volatile organic compounds were measured by gas chromatography and mass spectrometry in the breath of newly ventilated ICU patients within 24 h after ICU admission. Cytokines were measured in non-directed bronchial lavage fluid (NBL) and plasma by cytometric bead array. Correlation coefficients were calculated and presented in heatmaps.93 patients were included. Peroxidation products in exhaled breath were not associated with markers of inflammation in plasma, but were correlated with those in NBL. IL-6, IL-8, IL-1β and TNF-α concentration in NBL showed inverse correlation coefficients with the peroxidation products of fatty acids. Furthermore, NBL IL-10, IL-13, GM-CSF and IFNγ demonstrated positive associations with breath alkanes and alkenes. Correlation coefficients for NBL cytokines were high regarding peroxidation products of n-6, n-7 and particularly in n-9 fatty acids.Levels of lipid peroxidation products in the breath of ventilated ICU patients are associated with levels of inflammatory markers in NBL, but not in plasma. Alkanes and alkenes in breath seems to be associated with an anti-inflammatory, rather than a pro-inflammatory state in the alveoli.

Antioxidant activity of flavonoids isolated from young green barley leaves toward biological lipid samples.

PubMed

Benedet, John A; Umeda, Hisao; Shibamoto, Takayuki

2007-07-11

Natural plant flavonoids, saponarin/lutonarin=4.5/1, isolated from young green barley leaves were examined for their antioxidant activity using cod liver oil, omega-3 fatty acids, phospholipids, and blood plasma. The saponarin/lutonarin (S/L) mixture inhibited malonaldehyde (MA) formation from cod liver oil by 76.47+/-0.11% at a level of 1 micromol and 85.88+/-0.12% at a level of 8 micromol. The S/L mixture inhibited MA formation from the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by 45.60+/-1.08 and 69.24+/-0.24%, respectively, at a level of 8 micromol. The S/L mixture inhibited MA formation from the phospholipids lecithin I and II by 43.08+/-0.72 and 69.16+/-2.92%, respectively, at a level of 8 micromol. It also inhibited MA formation from blood plasma by 62.20+/-0.11% at a level of 8 micromol. The antioxidant activities obtained from the S/L mixture were comparable to those obtained from alpha-tocopherol and butylated hydroxy toluene (BHT) in all lipids tested.

Nonessential fatty acids in formula fat blends influence essential fatty acid metabolism and composition in plasma and organ lipid classes in piglets.

PubMed

Wall, K M; Diersen-Schade, D; Innis, S M

1992-12-01

The n-6 and n-3 fatty acid status of developing organs is the cumulative result of the diet lipid composition and many complex events of lipid metabolism. Little information is available, however, on the potential effects of the saturated fatty acid chain length (8:0-16:0) or oleic acid (18:1) content of the diet on the subsequent metabolism of the essential fatty acids 18:2n-6 and 18:3n-3 and their elongated/desaturated products. The effects of feeding piglets formulas with fat blends containing either coconut oil (12:0 + 14:0) or medium chain triglycerides (MCT, 8:0 + 10:0) but similar levels of 18:1, 18:2n-6 and 18:3n-3, or MCT with high or low 18:1 but constant 18:2n-6 and 18:3n-3 on the fatty acid composition of plasma, liver and kidney triglycerides, phospholipids and cholesteryl esters, and of brain total lipid, were studied. Diet-induced changes in the fatty acid composition of lipid classes were generally similar for plasma, liver and kidney. Dietary 18:1 content was reflected in tissue lipids and was inversely associated with levels of 18:2n-6. Lower percentage of 18:2n-6, however, was not associated with lower levels of its elongated/desaturated product 20:4n-6 but was associated with higher levels of 22:6n-3. Feeding coconut oil vs. MCT resulted in lower 18:1 levels in all lipids, and higher percentages of 20:4n-6 in tissue phospholipid. Increasing the dietary n-6/n-3 ratio from 5 to 8 significantly increased tissue percentage of 18:2n-6 and decreased phospholipid 22:6n-3.(ABSTRACT TRUNCATED AT 250 WORDS)

A pharmacologic increase in activity of plasma transaminase derived from small intestine in animals receiving an acyl CoA: diacylglycerol transferase (DGAT) 1 inhibitor.

PubMed

Yokoyama, Hideaki; Kobayashi, Akio; Kondo, Kazuma; Oshida, Shin-Ichi; Takahashi, Tadakazu; Masuyama, Taku; Shoda, Toshiyuki; Sugai, Shoichiro

2018-01-01

Acyl CoA: diacylglycerol acyltransferase (DGAT) 1 is an enzyme that catalyzes the re-synthesis of triglycerides (TG) from free fatty acids and diacylglycerol. JTT-553 is a DGAT1 inhibitor and exhibits its pharmacological action (inhibition of re-synthesis of TG) in the enterocytes of the small intestine leading to suppression of a postprandial elevation of plasma lipids. After repeated oral dosing JTT-553 in rats and monkeys, plasma transaminase levels were increased but there were neither changes in other hepatic function parameters nor histopathological findings suggestive of hepatotoxicity. Based on the results of exploratory studies for investigation of the mechanism of the increase in transaminase levels, plasma transaminase levels were increased after dosing JTT-553 only when animals were fed after dosing and a main factor in the diet contributing to the increase in plasma transaminase levels was lipids. After dosing JTT-553, transaminase levels were increased in the small intestine but not in the liver, indicating that the origin of transaminase increased in the plasma was not the liver but the small intestine where JTT-553 exhibits its pharmacological action. The increase in small intestinal transaminase levels was due to increased enzyme protein synthesis and was suppressed by inhibiting fatty acid-transport to the enterocytes. In conclusion, the JTT-553-related increase in plasma transaminase levels is considered not to be due to release of the enzymes from injured cells into the circulation but to be phenomena resulting from enhancement of enzyme protein synthesis in the small intestine due to the pharmacological action of JTT-553 in this organ.

[Comparison of long-chain polyunsaturated fatty acids in plasma and erythrocyte phospholipids for biological monitoring].

PubMed

Kawabata, Terue; Nakai, Kunihiko; Hagiwara, Chie; Kurokawa, Naoyuki; Murata, Katsuyuki; Yaginuma, Kozue; Satoh, Hiroshi

2011-01-01

Previous data have indicated that the erythrocyte membrane may be the preferred sample type for assessing long-chain polyunsaturated fatty acid (LCPUFA) contents in cardiac and cerebral membranes. In this epidemiological study, we examined whether plasma phospholipids can be used for accurate biological monitoring of the LCPUFA state or whether analysis of erythrocyte membrane phospholipids is indispensable. (1) The analysis of LCPUFA contents in erythrocyte membrane phospholipids was conducted at baseline and after 1 and 3 days at 4°C, and 21 days at -40°C, after blood drawing, and the changes in LCPUFA content were examined. (2) The LCPUFA compositions of plasma and erythrocyte phospholipids in 133 young women (18-30 years old) were examined and the relationships between the sample type and the levels of LCPUFAs were determined. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and DHA/arachidonic acid (AA) and (EPA+DHA)/AA ratios in erythrocyte membrane phospholipids after 21 days of blood drawing significantly decreased compared with the corresponding baseline data. Regarding AA, EPA and DHA, a significant positive correlation was shown between levels of erythrocyte membrane phospholipids and plasma phospholipids (AA, r=0.364; EPA, r=0.709; DHA, r=0.653). The predictive value of plasma phospholipids for determining the highest concentration quartile in erythrocyte phospholipids was better in EPA (70%) than in DHA (55%) and AA (42%). The measurement of LCPUFA content in erythrocyte membrane phospholipids is necessary for accurate biological monitoring. We also found that LCPUFA in erythrocyte membrane phospholipids is stable in cold storage (4°C) for 3 days after blood drawing.

Long chain polyunsaturated fatty acids (LCPUFAs) and nordihydroguaiaretic acid (NDGA) modulate metabolic and inflammatory markers in a spontaneous type 2 diabetes mellitus model (Stillman Salgado rats).

PubMed

Dain, Alejandro; Repossi, Gaston; Diaz-Gerevini, Gustavo T; Vanamala, Jairam; Das, Undurti N; Eynard, Aldo R

2016-11-25

Diabetes mellitus (DM) is a complex disease with alterations in metabolic and inflammatory markers. Stillman Salgado rats (eSS) spontaneously develop type 2 DM by middle age showing progressive impairment of glucose tolerance with hyperglycemia, hypertriglyceridemia and hyperinsulinemia. We analyzed the effects of supplementation of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) with or without nordihydroguaiaretic acid (NDGA) added, an antioxidant and lipoxygenase inhibitor, on metabolic and inflammatory parameters in eSS rats to evaluate whether they can delay development and/or prevent progression of DM. After weaning, eSS rats received, intraperitoneally, once a month ω-3 (EPA 35% and DHA 40%-6.25 mg/Kg) or ω-6 (90% arachidonic acid- 6. 25 mg/Kg) for twelve months. Two additional groups of rats received 1.9 mg/kg NDGA added to ω-3 and ω-6 fatty acids. Blood samples were collected at day 40, and at the end of the 6th month and 12th month of age to determine plasma triglycerides (TGs), total plasma fatty acids (FA), A1C hemoglobin (HbA1C), C-reactive protein (CRP), gamma glutamyl transpeptidase (GGT), lipo and hydro peroxides, nitrites and IL-6 (in plasma and liver, kidney, and pancreas) and underwent oral glucose tolerance test (OGTT) as well. Wistar and eSS rats that received saline solution were used as controls. Plasma lipids profile, TG, fasting and post-prandial blood glucose levels, and glycosylated HbA1C showed significant improvements in ω-3 and ω-3 + NDGA treated animals compared to eSS control group. ω-3 and ω-3 + NDGA groups showed an inverse correlation with fasting blood glucose and showed lower plasma levels of GGT, TG, and CRP. eSS rats treated with ω-3 LCPUFAs showed reduced level of inflammatory and oxidative indices in plasma and liver, kidney and pancreas tissues in comparison with eSS control (non-treated) and ω-6 treated groups. eSS rats are a useful model to study type 2 DM pathophysiology and related inflammatory indices. ω-3 + NDGA supplementation, at the doses tested, ameliorated inflammatory, metabolic and oxidative stress markers studied.

Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

PubMed

Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

2014-04-01

Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

Modulating efficacy of Rebaudioside A, a diterpenoid on antioxidant and circulatory lipids in experimental diabetic rats.

PubMed

Saravanan, Ramalingam; Ramachandran, Vinayagam

2013-09-01

The present study was to evaluate the protective effects of Rebaudioside A (Reb A) on antioxidant status and lipid profile in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats by a single intraperitoneal administration of STZ (40mg/kg b.w). Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, hydroperoxides and decreased levels of insulin. The activity of enzymatic antioxidants (superoxide dismutase, catalase and glutathione peroxidase) and the levels of non enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were decreased in diabetic rats. The levels of total cholesterol (TC), triglycerides (TGs), free fatty acids (FFAs), phospholipids (PLs), low density lipoproteins (LDL-cholesterol) and very low-density lipoproteins (VLDL-cholesterol) in the plasma significantly increased, while plasma high-density lipoproteins (HDL-cholesterol) were significantly decreased in diabetic rats. Oral administration of Reb A (200mg/kg b.w) brought back plasma glucose, insulin, lipid peroxidation products, enzymatic, non-enzymatic antioxidants and lipid profile levels to near normal. The results of the present investigation suggests that Reb A, a natural sweetener exhibits antilipid peroxidative, antihyperlipidemic and antioxidant properties. Copyright © 2013 Elsevier B.V. All rights reserved.

Identification of NaK-ATPase inhibitors in human plasma as nonesterified fatty acids and lysophospholipids.

PubMed

Kelly, R A; O'Hara, D S; Mitch, W E; Smith, T W

1986-09-05

Elevated plasma levels of factors with cardiac glycoside-like activity have been implicated in the response to volume expansion in animals and in the pathogenesis of certain human diseases. We recently described four fractions (IR1, EI1, EI2, EI3) from normal human plasma that inhibit NaK-ATPase, displace ouabain from the enzyme, and exhibit digoxin-like immunoreactivity (Kelly, R. A., O'Hara, D. S., Canessa, M. L., Mitch, W. E., and Smith, T. W. (1985) J. Biol. Chem. 260, 11396-11405). In this report, we identify the active component of these plasma fractions as long-chain nonesterified fatty acids (NEFA) and lysophospholipids. These lipids were present in fractions EI1, EI2, and EI3 in quantities sufficient to account for all of the NaK-ATPase inhibitory activity. The digoxin-like immunoreactivity in fraction IR1 could be attributed to hydrocortisone and other endogenous steroids. To explore the nature of the lipid-NaK-ATPase interactions, we examined the effects of various ATP or sodium concentrations on the NaK-ATPase activity measured in the presence of NEFA. Varying sodium did not affect the inhibition of NaK-ATPase by linoleic acid. At less than 0.15 mM ATP, linoleic acid stimulated NaK-ATPase, but at higher ATP concentrations, the enzyme was progressively inhibited. In summary, NEFA and lysophospholipids, at levels similar to those occurring in human plasma, may account for all of the NaK-ATPase inhibitory activity observed in human plasma fractions. These lipids probably do not directly regulate NaK-ATPase in vivo under normal physiologic conditions, but may alter the sodium pump in disease states characterized by abnormalities in lipid metabolism or plasma protein binding.

Encapsulated fish oil enriched in alpha-tocopherol alters plasma phospholipid and mononuclear cell fatty acid compositions but not mononuclear cell functions.

PubMed

Yaqoob, P; Pala, H S; Cortina-Borja, M; Newsholme, E A; Calder, P C

2000-03-01

Several studies have reported that dietary fish oil (FO) supplementation alters cytokine production and other functional activities of peripheral blood mononuclear cells (PBMC). However, few of these studies have been placebo controlled and few have related the functional changes to alterations in PBMC fatty acid composition Healthy subjects supplemented their diets with 9 g day-1 of encapsulated placebo oil (3 : 1 mix of coconut and soybean oils), olive oil (OO), safflower oil (SO), evening primrose oil (EPO) or FO [providing 2.1 g eicosapentaenoic acid (EPA) plus 1.1 g docosahexaenoic acid (DHA) per day] for 12 weeks; the capsules also provided 205 mg alpha-tocopherol per day. Blood was sampled at 4-weekly intervals and plasma and PBMC prepared. Plasma phospholipid and PBMC fatty acid composition, plasma alpha-tocopherol and thiobarbituric acid-reactive substance concentrations, plasma total antioxidant capacity, the proportions of different PBMC subsets, the proportions of PBMC expressing the adhesion molecules CD2, CD11b and CD54, and PBMC functions (lymphocyte proliferation, natural killer cell activity, cytokine production) were measured. All measurements were repeated after a 'washout' period of 8 weeks. The placebo, OO and SO capsules had no effect on plasma phospholipid or PBMC fatty acid composition. The proportion of dihomo-gamma-linolenic acid in plasma phospholipids was elevated in subjects taking EPO and was decreased in subjects taking FO. There was no appearance of gamma-linolenic acid in the plasma phospholipids or PBMC in subjects taking EPO. There was a marked increase in the proportion of EPA in the plasma phospholipids (10-fold) and PBMC (four-fold) of subjects taking FO supplements; this increase was maximal after 4 weeks of supplementation. There was an increase in the proportion of DHA in plasma phospholipids and PBMC, and an approximately 20% decrease in the proportion of arachidonic acid in plasma phospholipids and PBMC, during FO supplementation. Plasma concentrations of alpha-tocopherol were significantly elevated during supplementation in all subjects and returned to baseline values after the washout period. There were no effects of supplementation with any of the capsules on total plasma antioxidant activity or plasma thiobarbituric acid-reactive substances or on the proportion of different PBMC subsets, on the proportion of PBMC expressing adhesion molecules, on natural killer cell activity, on the proliferation of mitogen-stimulated whole blood cultures or PBMC, or on the ex vivo production of a range of cytokines by whole blood cultures or PBMC cultures stimulated by either concanavalin A or lipopolysaccharide. Supplementation of the diet with 3.2 g EPA plus DHA per day markedly alters plasma phospholipid and PBMC fatty acid compositions. The lack of effect of FO upon PBMC functions may relate to the level of alpha-tocopherol included in the supplements.

The pH dependence of silicon-iron interaction in rats.

PubMed

Jia, X; Emerick, R J; Kayongo-Male, H

1997-01-01

A 2 x 2 x 3 factorial experiment was conducted to study the pH dependence of a silicon-iron interaction in vivo. The dietary treatments used in the factorial design were the following (mg/kg of diet): silicon, 0 and 500; iron, 35 and 187; acid-base, ammonium chloride as 0.5% of total diet (acidic), sodium bicarbonate as 1.0% of total diet (basic), or no supplementation of acid or base (control). The supplementation of 500 mg silicon/kg of diet increased plasma-iron concentration in rats fed the acidic or control diets, but not in rats fed the basic diet. A high dietary-iron level suppressed copper absorption and utilization and subsequently imposed a negative effect on its own utilization. An increase in the plasma total-cholesterol concentration caused by high dietary-iron level was likely a consequence of the antagonistic effect of iron on copper absorption and utilization. The use of cupric sulfate pentahydrate as the dietary-copper source in this study resulted in plasma copper concentrations that were approximately twice those obtained in a related study using cupric carbonate. Also, a 42% coefficient of variation (C.V.) for plasma-copper concentrations of rats fed cupric sulfate in this study was greatly reduced from the C.V. = 108% previously associated with the dietary cupric carbonate.

Effectiveness of a flow-based device using riboflavin photochemistry in damaging blood-borne viral nucleic acids.

PubMed

Zhu, Liguo; Tong, Hongli; Wang, Shufang; Yu, Yang; Liu, Zhong; Li, Changqing; Wang, Deqing

2018-05-03

Effectiveness of a flow-based treatment device using riboflavin photochemistry was demonstrated by cytopathic effect method using indicator viruses. However, inactivation efficacy against real blood-borne viruses needs to be evaluated, especially at nucleic acid level. Special plasma samples with varying concentrations of blood-borne virus were selected using a strict blood selection procedure and were treated with device treatment (DT). Nucleic acid test (NAT) using polymerase chain reaction fluorescence method was used to detect virus copies. The NAT value of 4325 in plasma with high Hepatitis B Virus (HBV) concentrations decreased to 1330 with DT. After 100-fold dilution, the NAT value was below the NAT detection limits with DT compared with 23.0 that without DT. The NAT value of 61.9 in plasma with medium HBV concentrations decreased to 37.8 with DT, and after 10-fold dilution, the NAT value was below the NAT detection limits with DT compared with below 20 that without DT. The Ct values of plasma with low concentrations of blood-borne viruses were below the NAT detection limits with DT. There was a dose effect with DT which was effective in blood-borne viruses damaging nucleic acids to a level below the NAT detection limits. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed

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

2005-02-07

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

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

PubMed Central

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

2005-01-01

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

Endogenous glucocorticoids exacerbate cholestasis-associated liver injury and hypercholesterolemia in mice

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

Geest, Rick van der, E-mail: r.van.der.geest@lacdr

Cholestatic liver disease is characterized by a disruption of bile flow, bile acid toxicity, liver injury, and hypercholesterolemia. Relatively high secretion of glucocorticoids by the adrenals has been observed under cholestatic conditions. Here we investigated a contribution of the rise in endogenous glucocorticoids to initial stage cholestasis pathology. Adrenalectomized or sham-operated control C57BL/6 mice were given an oral dose of alpha-naphthylisothiocyanate to induce cholestasis. Adrenalectomy effectively lowered plasma corticosterone levels (18 ± 5 ng/ml vs 472 ± 58 ng/ml; P < 0.001) and disrupted the metabolic and anti-inflammatory glucocorticoid function. Adrenal removal did not exacerbate the cholestasis extent. In contrast,more » the cholestasis-associated liver injury was markedly lower in adrenalectomized mice as compared to controls as evidenced by a 84%–93% decrease in liver necrosis and plasma alanine aminotransferase and bile acid levels (P < 0.001 for all). Gene expression analysis on livers from adrenalectomized mice suggested the absence of bile acid toxicity-associated farnesoid X receptor signaling in the context of a 44% (P < 0.01) and 82% (P < 0.001) reduction in sodium/bile acid cotransporter member 1 transcript level as compared to respectively control and non-diseased mice. Adrenalectomy reduced the expression of the cholesterol synthesis gene HMG-CoA reductase by 70% (P < 0.05), which translated into a 73% lower plasma total cholesterol level (P < 0.05). Treatment of C57BL/6 mice with the glucocorticoid receptor antagonist RU-486 recapitulated the protective effect of adrenalectomy on indices of liver injury and hypercholesterolemia. In conclusion, we have shown that endogenous glucocorticoids exacerbate the liver injury and hypercholesterolemia associated with acute cholestasis in mice. - Highlights: • Cholestasis is associated with increased plasma glucocorticoid levels in mice. • Adrenalectomy lowers cholestasis-associated liver injury and hypercholesterolemia. • GR antagonist RU-486 similarly improves the cholestasis phenotype. • Endogenous glucocorticoids promote re-uptake of circulating bile acids into liver.« less

Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos

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

Egloff, Caroline; Crump, Doug, E-mail: doug.crump@ec.gc.ca; Porter, Emily

The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highestmore » doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • TBOEP is not embryolethal to chicken embryos. • TEP affected embryonic viability, morphometric endpoints, and thyroid hormone levels. • TEP altered mRNA levels of xenobiotic and lipid metabolism genes. • TEP increased plasma bile acids and caused gallbladder hypotrophy. • TEP elicited more adverse molecular and phenotypic effects than TBOEP.« less

Uric acid in major depressive and anxiety disorders.

PubMed

Black, Catherine N; Bot, Mariska; Scheffer, Peter G; Snieder, Harold; Penninx, Brenda W J H

2018-01-01

Uric acid has neuroprotective effects, owing to its antioxidant properties. Lowered antioxidant capacity, causing increased oxidative stress, may be involved in affective disorders and might be altered by antidepressants. This study investigated the association of plasma uric acid, the greatest contributor to blood antioxidant capacity, with major depressive disorder (MDD) and anxiety disorders. Data were from the Netherlands Study of Depression and Anxiety including patients with current (N = 1648), remitted (N = 609) MDD and/or anxiety disorders (of which N = 710 antidepressant users) and 618 controls. Diagnoses were established with the Composite International Diagnostic Interview. Symptom severity was assessed with the Inventory of Depressive Symptoms-Self Report, Beck Anxiety Inventory and Fear Questionnaire. Uric acid was measured in plasma. Analyses were adjusted for sociodemographic, health and lifestyle variables. Plasma uric acid adjusted mean levels were lower in current MDD and/or anxiety disorder(s) (289μmol/l) compared to remitted disorders (298μmol/l, p < .001) and controls (299μmol/l, p < .001; Cohen's d .10). This finding was independent of antidepressant use. Depressive (β-.05, p = .0012), anxiety (β-.04, p = .009) and phobic (β-.03, p = .036) symptom severity, and symptom duration (β-.04, p = .009) were negatively associated with uric acid. Limitations include the lack of data on dietary intake which could be a potential confounding factor. From these cross-sectional findings, the association between uric acid and psychopathology cannot be inferred to be causal. This large scale study finds plasma uric acid levels are lower in current, but not remitted, MDD and/or anxiety disorders, according to a dose-response gradient. This suggests the involvement of decreased antioxidant status in affective disorders, and points to their potential as an avenue for treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

1H-NMR-Based Metabolic Profiling of Maternal and Umbilical Cord Blood Indicates Altered Materno-Foetal Nutrient Exchange in Preterm Infants

PubMed Central

Küster, Alice; Guignard, Nadia; Alexandre–Gouabau, Marie-Cécile; Darmaun, Dominique; Robins, Richard J.

2012-01-01

Background Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used 1H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth. Methodology The metabolic profile in 1H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates. Principal Findings Clear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood. Conclusion These results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants. PMID:22291897

Potential use of nutritional factors to optimize performance under stress

NASA Technical Reports Server (NTRS)

Munro, H. N.

1977-01-01

A study of the effects of amino acids on hypothalamo-pituitary capacity to secrete ACTH, and the response of the adrenal gland in terms of corticosterone level in the plasma was discussed in the first part of this report. Second, the report includes a study of the response of protein metabolism in various levels of corticosterone elevation in the plasma. This second part is regarded as having considerable significance for space travel, since this data indicate a threshold level of plasma corticosteroids above which there is increased catabolism of muscle protein.

Pharmacokinetics and metabolism of all-trans- and 13-cis-retinoic acid in pulmonary emphysema patients.

PubMed

Muindi, Josephia R; Roth, Michael D; Wise, Robert A; Connett, John E; O'Connor, George T; Ramsdell, Joe W; Schluger, Neil W; Romkes, Marjorie; Branch, Robert A; Sciurba, Frank C

2008-01-01

Retinoids promote lung alveolarization in animal models and were administered to patients as part of the Feasibility of Retinoid Therapy for Emphysema (FORTE) study. This FORTE substudy investigated the pharmacokinetic profiles of 2 retinoic acid isomers-all-trans-retinoic acid (ATRA) and 13-cis-retinoic acid (13-cRA)-in subjects with emphysema, evaluated strategies to overcome self-induced ATRA catabolism, and identified pharmacodynamic relationships. Comprehensive and limited pharmacokinetics were obtained at multiple visits in emphysema subjects treated with placebo (n = 30), intermittent dosing (4 days/week) with low-dose ATRA (1 mg/kg/day, n = 21), or high-dose ATRA (2 mg/kg/day, n = 25) or daily administration of 13-cRA (1 mg/kg/day, n = 40). High-dose ATRA produced the highest peak plasma ATRA Cmax. However, at follow-up, plasma ATRA C(max) was significantly decreased from baseline in subjects whose day 1 levels exceeded 100 ng/mL (P < .0001). In contrast, administration of 13-cRA produced lower plasma ATRA C(max) (<100 ng/mL), but the levels were significantly higher at follow-up than those on day 1 (P < .001). Plasma ATRA levels as determined on day 1 correlated with changes in pulmonary diffusing capacity at 6 months, consistent with concentration-dependent biologic effects (r2 = -0.25). The authors conclude that intermittent therapy with high-dose ATRA produced the greatest ATRA exposure, but alternative approaches for limiting self-induced ATRA catabolism should be sought.

Measurement of plasma homovanillic acid concentrations in schizophrenic patients.

PubMed

Kaminski, R; Powchick, P; Warne, P A; Goldstein, M; McQueeney, R T; Davidson, M

1990-01-01

1. Several lines of evidence suggest that abnormalities of central dopaminergic transmission may be involved in the expression of some schizophrenic symptoms. However, elucidation of the role of dopamine (DA) in schizophrenia has eluded investigative efforts partially because no accurate and easily repeatable measure of brain DA activity exists. 2. The development of a technique to measure homovanillic acid in plasma has offered the possibility of performing serial measurements of this major DA metabolite. 3. Assuming that plasma homovanillic acid (PHVA) concentrations is an index of brain DA activity, measurement of PHVA can play a role in elucidating the DA abnormality in schizophrenia. 4. Results to date suggest that plasma homovanillic acid concentrations are lower in chronic schizophrenic patients compared to normal controls, and that PHVA values correlate with schizophrenic symptom severity. 5. In addition, PHVA levels were shown to initially rise and subsequently decline during chronic neuroleptic administration in treatment responsive but not in treatment refractory schizophrenic patients.

Plasma fluctuation in estradiol-17β and bone resorption markers around parturition in dairy cows

PubMed Central

DEVKOTA, Bhuminad; TAKAHASHI, Masahiro; SATO, Saori; SASAKI, Kouya; UEKI, Atsushi; OSAWA, Takeshi; TAKAHASHI, Masahiro; YAMAGISHI, Norio

2015-01-01

Blood samples were obtained sequentially from 10 dairy cows around the time of parturition to assess plasma fluctuations in estradiol-17β (E2) levels in association with those of several bone resorption markers. Plasma E2 concentration increased sharply a few days prepartum and decreased quickly after parturition. In terms of bone resorption markers, the plasma level of tartrate-resistant acid phosphatase isoform 5b (TRAP5b) rose significantly, commencing 1 week prepartum, and was maintained at this level to a few days postpartum. The plasma concentration of carboxyterminal collagen cross-links of type-I collagen (CTx) increased significantly after parturition. These observations suggest that osteoclast-mediated bone resorption was activated after parturition when plasma E2 concentrations decreased. PMID:25755022

Plasma fluctuation in estradiol-17β and bone resorption markers around parturition in dairy cows.

PubMed

Devkota, Bhuminad; Takahashi, Masahiro; Sato, Saori; Sasaki, Kouya; Ueki, Atsushi; Osawa, Takeshi; Takahashi, Masahiro; Yamagishi, Norio

2015-07-01

Blood samples were obtained sequentially from 10 dairy cows around the time of parturition to assess plasma fluctuations in estradiol-17β (E2) levels in association with those of several bone resorption markers. Plasma E2 concentration increased sharply a few days prepartum and decreased quickly after parturition. In terms of bone resorption markers, the plasma level of tartrate-resistant acid phosphatase isoform 5b (TRAP5b) rose significantly, commencing 1 week prepartum, and was maintained at this level to a few days postpartum. The plasma concentration of carboxyterminal collagen cross-links of type-I collagen (CTx) increased significantly after parturition. These observations suggest that osteoclast-mediated bone resorption was activated after parturition when plasma E2 concentrations decreased.

Plasma Amyloid β-Protein and C-reactive Protein in Relation to the Rate of Progression of Alzheimer Disease

PubMed Central

Locascio, Joseph J.; Fukumoto, Hiroaki; Yap, Liang; Bottiglieri, Teodoro; Growdon, John H.; Hyman, Bradley T.; Irizarry, Michael C.

2008-01-01

Objective To examine whether plasma markers of amyloid precursor protein metabolism (amyloid β-protein ending in Val-40 [Aβ40] and Ala-42 [Aβ42]), inflammation (high-sensitivity C-reactive protein), and folic acid metabolism (folic acid, vitamin B12, and total homocysteine levels) are associated with the rate of cognitive and functional decline in persons with Alzheimer disease. Design Longitudinal study across a mean (SD) of 4.2 (2.6) years with assessments at approximately 6- to 12- month intervals. Setting Out patient care. Patients A cohort of 122 patients having a clinical diagnosis of probable Alzheimer disease, each with at least 2 assessments across time. Main Outcome Measures Scores on the cognitive Information-Memory-Concentration subscale of the Blessed Dementia Scale and the functional Weintraub Activities of Daily Living Scale. Results Low plasma levels of Aβ40, Aβ42, and high-sensitivity C-reactive protein were associated with a significantly more rapid cognitive decline, as indexed using the Blessed Dementia Scale, than were high levels. Low levels of Aβ42 and high-sensitivity C-reactive protein were significantly associated with more rapid functional decline on the Weintraub Activities of Daily Living Scale than were high levels. These plasma markers contributed about 5% to 12% of the variance accounted for on the Blessed Dementia Scale and the Activities of Daily Living Scale by fixed-effects predictors. Measures of folic acid metabolism were not associated with changes on either the Blessed Dementia Scale or the Activities of Daily Living Scale. Conclusions Plasma markers of amyloid precursor protein metabolism and C-reactive protein may be associated with the rate of cognitive and functional decline in patients with Alzheimer disease. PMID:18541797

Lack of effect of laboratory-provoked anxiety on plasma homovanillic acid concentration in normal subjects.

PubMed

Zemishlany, Z; Davidson, M

1996-08-15

The present study was undertaken to investigate if acute anxiety can affect plasma concentrations of homovanillic acid (pHVA). Since elevated pHVA levels have been associated with severity of schizophrenic symptoms, the results of this study will help determine if the pHVA elevations are directly related to psychosis or if anxiety is also a contributory factor. Anxiety was provoked in 10 young normal subjects by a combined paradigm of mental arithmetic task and threat of electrical shock. A significant increase in self-ratings of anxiety, blood pressure, and plasma levels of norepinephrine, 3-methoxy-4-hydroxyphenylethyleneglycol and growth hormone indicated that the paradigm used was effective in provoking anxiety; however, anxiety did not affect pHVA concentrations. The results may support the notion that increased pHVA levels in severely ill schizophrenic patients are related to the schizophrenic pathophysiology rather than to anxiety.

Micro determination of plasma and erythrocyte copper by atomic absorption spectrophotometry

PubMed Central

Blomfield, Jeanette; Macmahon, R. A.

1969-01-01

The free and total plasma copper and total erythrocyte copper levels have been determined by simple, yet sensitive and highly specific methods, using atomic absorption spectrophotometry. For total copper determination, the copper was split from its protein combination in plasma or red cells by the action of hydrochloric acid at room temperature. The liberated copper was chelated by ammonium pyrrolidine dithiocarbamate and extracted into n-butyl acetate by shaking and the organic extract was aspirated into the atomic absorption spectrophotometer flame. The entire procedure was carried out in polypropylene centrifuge tubes, capped during shaking. For the free plasma copper measurement the hydrochloric acid step was omitted. Removal of the plasma or erythrocyte proteins was found to be unnecessary, and, in addition, the presence of trichloracetic acid caused an appreciable lowering of absorption. Using a double-beam atomic absorption spectrophotometer and scale expansion × 10, micro methods have been derived for determining the total copper of plasma or erythrocytes with 0·1 ml of sample, and the free copper of plasma with 0·5 ml. The macro plasma copper method requires 2 ml of plasma and is suitable for use with single-beam atomic absorption spectrophotometers. With blood from 50 blood donors, normal ranges of plasma and erythrocyte copper have been determined. PMID:5776543

Maternal dietary fat affects milk fatty acid profile and impacts on weight gain and thermogenic capacity of suckling rats.

PubMed

Priego, Teresa; Sánchez, Juana; García, Ana Paula; Palou, Andreu; Picó, Catalina

2013-05-01

We aimed to assess the effects of maternal supplementation with the main fat sources used in the human Western diet (olive oil, butter, margarine) on milk FA composition and on plasma FA profile of offspring, and to determine whether it may influence body-weight-gain (BWG) and adiposity of offspring during the suckling period. Wistar rats were supplemented with the different fat sources from day 14 of gestation and throughout lactation. Olive oil-supplemented dams showed the highest proportion of oleic-acid in milk, with no changes in plasma. Their offspring also showed the highest proportion of this FA in plasma, lower BWG during the suckling period, and higher levels of UCP1 in brown adipose tissue (BAT) at weaning. Margarine-supplemented dams showed the highest percentage of PUFA in milk, and a similar tendency was found in plasma of their offspring. Butter-supplemented dams displayed higher proportion of saturated FA (SFA) in milk compared to other fat-supplemented dams, but lower than controls. Control offspring also showed higher proportion of SFA in plasma and greater BWG during the suckling period than fat-supplemented groups. Significant correlations were found between the relative content of some milk FA and BWG of offspring, in particular, oleic-acid levels correlated negatively with BWG and positively with UCP1 levels. These results show that maternal dietary source of fat affects milk FA composition and circulating FA profile, as could be expected, but also BWG and thermogenic capacity of offspring during the suckling period. An effect of oleic-acid stimulating BAT thermogenic capacity of suckling pups is proposed.

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

PubMed

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

2011-01-20

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

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice.

PubMed

Seto, Sai Wang; Lam, Tsz Yan; Or, Penelope Mei Yu; Lee, Wayne Yuk Wai; Au, Alice Lai Shan; Poon, Christina Chui Wa; Li, Rachel Wai Sum; Chan, Shun Wan; Yeung, John Hok Keung; Leung, George Pak Heng; Lee, Simon Ming Yuen; Ngai, Sai Ming; Kwan, Yiu Wa

2010-09-01

Folic acid supplementation provides beneficial effects on endothelial functions in patients with hyperhomocysteinemia. However, its effects on vascular functions under diabetic conditions are largely unknown. Therefore, the effect(s) of folic acid (5.7 and 71 microg/kg/day for 4 weeks) on aortic relaxation was investigated using obese/diabetic (+db/+db) mice and lean littermate (+db/+m) mice. Acetylcholine-induced relaxation in +db/+db mice was less than that observed in +db/+m mice. The reduced relaxation in +db/+db mice was restored by consumption of 71 microg/kg folic acid. Acetylcholine-induced relaxation (with and without folic acid treatment) was sensitive to N(G)-nitro-L-arginine methyl ester, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, geldanamycin and triciribine. In addition, acetylcholine-induced relaxation was attenuated by resistin. The plasma level of resistin in +db/+db mice was sevenfold higher than that measured in +db/+m mice, and the elevated plasma level of resistin in +db/+db mice was reduced by 25% after treatment with 71 microg/kg folic acid. Folic acid slightly increased the ratio of reduced glutathione to oxidized glutathione in +db/+db mice. Moreover, folic acid caused a reduction in PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression, an increase in the phosphorylation of endothelial nitric oxide synthase (eNOS(Ser1177)) and Akt(Ser473), and an enhanced interaction of heat shock protein 90 (HSP90) with eNOS in both strains, with greater magnitude observed in +db/+db mice. In conclusion, folic acid consumption improved blunted acetylcholine-induced relaxation in +db/+db mice. The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state. Copyright 2010 Elsevier Inc. All rights reserved.

ToF-SIMS study of differentiation of human bone-derived stromal cells: new insights into osteoporosis.

PubMed

Schaepe, Kaija; Werner, Janina; Glenske, Kristina; Bartges, Tessa; Henss, Anja; Rohnke, Marcus; Wenisch, Sabine; Janek, Jürgen

2017-07-01

Lipids have numerous important functions in the human body, as they form the cells' plasma membranes and play a key role in many disease states, presumably also in osteoporosis. Here, the fatty acid composition of the outer plasma membranes of cells differentiated into the osteogenic and adipogenic direction is studied with surface-sensitive time-of-flight secondary ion mass spectrometry (ToF-SIMS). For data evaluation, principal component analysis (PCA) is applied. Human (bone-derived) mesenchymal stromal cells (hMSCs) from an osteoporotic donor and a control donor are compared to reveal differences in the fatty acid composition of the membranes. The chemical information is correlated to staining and real-time quantitative polymerase chain reaction (rt-qPCR) results to provide insight into the gene expression of several differentiation markers on the RNA level. Adipogenic differentiation of hMSCs from a non-osteoporotic donor correlates with increased relative intensities of all fatty acids under investigation. After osteogenic differentiation of non-osteoporotic cells, the relative mass signal intensities of unsaturated fatty acids such as oleic and linoleic acids are increased. However, the osteoporotic cells show increased levels of palmitic acid in the plasma membrane after exposure to osteogenic differentiation conditions, which correlates to an immature differentiation state relative to non-osteoporotic osteogenic cells. This immature differentiation state is confirmed by increased early osteogenic differentiation factor Runx2 on RNA level and by less calcium mineralization spots seen in von Kossa staining and ToF-SIMS images. Graphical abstract Time-of-flight secondary ion mass spectrometry is applied to analyze the fatty acid composition of the outer plasma membranes of cells differentiated into the adipogenic and osteogenic direction. Cells from an osteoporotic and a control donor are compared to reveal differences due to differentiation and disease stage of the cells.

Amino acid transmitters in patients with headache during the acute phase of cerebrovascular ischemic disease.

PubMed

Castillo, J; Martínez, F; Corredera, E; Aldrey, J M; Noya, M

1995-11-01

The pathophysiology of headache occurring at stroke onset is unknown. Migraine and ischemia share an excessive release of neuroexcitatory amino acids. Inhibitory amino acids also may be implicated in both diseases. We investigated whether fluctuations of these amino acids occur in headache accompanying cerebral infarction. We studied 100 patients with infarction in the territory of the middle cerebral artery. Neurological impairment was assessed using the Canadian Neurological Scale and Barthel Index. Size of infarction was determined with CT. Twenty-eight patients developed headache. Glutamate, aspartate, and taurine were quantified in blood and cerebrospinal fluid (CSF) within 24 hours of stroke onset with cationic exchange chromatography. Stroke subtypes, size of infarct on CT, and clinical scales were similar in patients with and without headache. Plasma glutamate level was 321.14 +/- 149.53 mumol/L in patients with headache and 233 +/- 107.23 mumol/L in those without headache (P < .005). Glutamate in CSF was higher in patients with headache (4.6 +/- 1.49 mumol/L) than in patients without headache (3.11 +/- 1.18 mumol/L) (P < .001). Aspartate concentrations in plasma and CSF were similar in both groups. Taurine concentrations in plasma were 103.10 +/- 52.82 mumol/L and 177.49 +/- 90.92 mumol/L in headache and nonheadache patients, respectively (P < .001). Taurine levels in CSF were 5.42 +/- 2.42 mumol/L in patients with headache and 9.27 +/- 5.31 mumol/L in those without headache (P < .001). No significant correlation was found between amino acid levels in plasma or CSF and size of infarction. Amino acid neurotransmitters play a role in the pathophysiology of headache that occurs at the onset of stroke. The ischemic penumbral area, more than the infarction itself, may cause a state of cortical hyperexcitability that would be responsible for the cortical release of amino acids and the induction of headache by altering pain perception mechanisms.

Effect of plasma homocysteine level and urinary monomethylarsonic acid on the risk of arsenic-associated carotid atherosclerosis

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

Wu, M.-M.; Graduate Institute of Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan; Chiou, H.-Y.

2006-10-01

Arsenic-contaminated well water has been shown to increase the risk of atherosclerosis. Because of involving S-adenosylmethionine, homocysteine may modify the risk by interfering with the biomethylation of ingested arsenic. In this study, we assessed the effect of plasma homocysteine level and urinary monomethylarsonic acid (MMA{sup V}) on the risk of atherosclerosis associated with arsenic. In total, 163 patients with carotid atherosclerosis and 163 controls were studied. Lifetime cumulative arsenic exposure from well water for study subjects was measured as index of arsenic exposure. Homocysteine level was determined by high-performance liquid chromatography (HPLC). Proportion of MMA{sup V} (MMA%) was calculated bymore » dividing with total arsenic species in urine, including arsenite, arsenate, MMA{sup V}, and dimethylarsinic acid (DMA{sup V}). Results of multiple linear regression analysis show a positive correlation of plasma homocysteine levels to the cumulative arsenic exposure after controlling for atherosclerosis status and nutritional factors (P < 0.05). This correlation, however, did not change substantially the effect of arsenic exposure on the risk of atherosclerosis as analyzed in a subsequent logistic regression model. Logistic regression analyses also show that elevated plasma homocysteine levels did not confer an independent risk for developing atherosclerosis in the study population. However, the risk of having atherosclerosis was increased to 5.4-fold (95% CI, 2.0-15.0) for the study subjects with high MMA% ({>=}16.5%) and high homocysteine levels ({>=}12.7 {mu}mol/l) as compared to those with low MMA% (<9.9%) and low homocysteine levels (<12.7 {mu}mol/l). Elevated homocysteinemia may exacerbate the formation of atherosclerosis related to arsenic exposure in individuals with high levels of MMA% in urine.« less

Urinary Liver Type Fatty Acid Binding Protein Is Negatively Associated With Estimated Glomerular Filtration Rate in Renal Transplant Recipients With Graft Loss.

PubMed

Huang, Y-C; Chang, Y-S; Chen, C-C; Tsai, S-F; Yu, T-M; Wu, M-J; Chen, C-H

2018-05-01

Liver type fatty acid binding protein (L-FABP) is abundant not only in the liver but also in the kidney and is excreted in urine. Its primary function is to facilitate intracellular long chain fatty acid transport and it might also act as an endogenous antioxidant molecular. The purpose of this study was to investigate whether plasma or urinary L-FABP levels were associated with graft function in renal transplant recipients. Sixty-seven renal transplant recipients with a mean age of 48.8 years were recruited. The mean duration of renal transplantation was 4131 days. Recipients were divided into 2 groups based on their estimated glomerular filtration rate (eGFR) values: moderate graft function (eGFR ≥60 mL/min/1.73 m 2 ) and low graft function (eGFR <60 mL/min/1.73 m 2 ). Fasting plasma and urinary L-FABP levels were measured. There was no significant difference in plasma L-FABP level between the 2 groups, although recipients in the low graft function group had significantly lower urinary L-FABP level when compared with recipients in the moderate graft function group. Plasma and urinary L-FABP levels were not associated with eGFR in the 67 recipients; however, urinary L-FABP level (β = -1.24, P = .037) and level adjusted by urinary creatinine (β = -0.75, P = .046) were significantly negatively associated with eGFR in recipients with low graft function after adjusting for potential confounders. Increased urinary L-FABP level seems to be a significant indicator of decreased graft function in renal transplant recipients with loss of graft function. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet.

PubMed

Xie, Z X; Xia, S F; Qiao, Y; Shi, Y H; Le, G W

2015-06-01

Increased levels of plasma free amino acids (pFAAs) can disturb the blood glucose levels in patients with obesity, diabetes mellitus and metabolic syndrome (MS) and are associated with enhanced protein oxidation. Oxidation of proteins, especially in the muscles, can promote protein degradation and elevate the levels of pFAAs. Gamma-aminobutyric acid (GABA), a food additive, can reduce high-fat diet (HFD)-induced hyperglycaemia; however, the mechanisms remain unclear. The aim of this study was to evaluate the effects of GABA on protein oxidation and pFAAs changes. One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose-dependently inhibited body weight gains, muscular oxidation and protein degradation. While medium and low doses of GABA mitigated HFD-induced pFAA disorders, the high dose of GABA deteriorated the pFAA disorders. Medium dose of GABA increased the levels of GABA, but high dose of GABA reduced the levels of plasma GABA and increased the activity of succinic semialdehyde dehydrogenase in the liver. Therefore, treatment with GABA mitigated HFD-induced hyperglycaemia probably by repairing HFD-induced muscular oxidative stress and pFAA disorders in mice. Our data also suggest that an optimal dose of GABA is crucial for the prevention of excess GABA-related decrease in the levels of pFAA and GABA as well as obesity. Journal of Animal Physiology and Animal Nutrition © 2014 Blackwell Verlag GmbH.

Salmon diet in patients with active ulcerative colitis reduced the simple clinical colitis activity index and increased the anti-inflammatory fatty acid index--a pilot study.

PubMed

Grimstad, Tore; Berge, Rolf K; Bohov, Pavol; Skorve, Jon; Gøransson, Lasse; Omdal, Roald; Aasprong, Ole G; Haugen, Margaretha; Meltzer, Helle M; Hausken, Trygve

2011-02-01

Data concerning the anti-inflammatory effect of dietary n-3 polyunsaturated fatty acids (PUFAs) in patients with ulcerative colitis (UC) are inconsistent. Salmon fillet contains n-3 PUFAs and bioactive peptides that may improve its effects compared to fish oil alone. We assessed the efficacy of a salmon-rich diet in patients with mild ulcerative colitis. An 8-week intervention pilot study was designed to assess the effects of 600 grams Atlantic salmon consumption weekly in 12 UC patients. Simple clinical colitis activity index (SCCAI), a dietary questionnaire, sigmoidoscopy, selected serum inflammatory markers, fecal calprotectin, and plasma and rectal biopsy fatty acid profiles were assessed before and after intervention. The levels of C20:4n-6 arachidonic acid in biopsies after dietary intervention were correlated with histology and endoscopy scores. The concentrations of n-3 PUFAs, C20:5n-3 eicosapentaenoic acid, C22:6n-3 docosahexaenoic acid, and the n-3/n-6 ratio increased in plasma and rectal biopsies. The anti-inflammatory fatty acid index (AIFAI) increased both in biopsies and plasma accompanied with a significantly reduced SCCAI. Based on evidence of SCCAI and AIFAI and a tendency of decreased levels of CRP and homocysteine, intake of Atlantic salmon may have beneficial effects on disease activity in patients with mild ulcerative colitis.

Dietary saturated and monounsaturated fats protect against acute acetaminophen hepatotoxicity by altering fatty acid composition of liver microsomal membrane in rats

PubMed Central

2011-01-01

Background Dietary polyunsaturated fats increase liver injury in response to ethanol feeding. We evaluated the effect of dietary corn oil (CO), olive oil (OO), and beef tallow (BT) on fatty acid composition of liver microsomal membrane and acute acetaminophen hepatotoxicity. Methods Male Sprague-Dawley rats were fed 15% (wt/wt) CO, OO or BT for 6 weeks. After treatment with acetaminophen (600 mg/kg), samples of plasma and liver were taken for analyses of the fatty acid composition and toxicity. Results Treatment with acetaminophen significantly elevated levels of plasma GOT and GPT as well as hepatic TBARS but reduced hepatic GSH levels in CO compared to OO and BT groups. Acetaminophen significantly induced protein expression of cytochrome P450 2E1 in the CO group. In comparison with the CO diet, lower levels of linoleic acid, higher levels of oleic acids and therefore much lower ratios of linoleic to oleic acid were detected in rats fed OO and BT diets. Conclusions Dietary OO and BT produces similar liver microsomal fatty acid composition and may account for less severe liver injury after acetaminophen treatment compared to animals fed diets with CO rich in linoleic acid. These findings imply that types of dietary fat may be important in the nutritional management of drug-induced hepatotoxicity. PMID:22011590

Effect of intravenous omega-3 fatty acid infusion and hemodialysis on fatty acid composition of free fatty acids and phospholipids in patients with end-stage renal disease.

PubMed

Madsen, Trine; Christensen, Jeppe Hagstrup; Toft, Egon; Aardestrup, Inge; Lundbye-Christensen, Søren; Schmidt, Erik B

2011-01-01

Patients treated with hemodialysis (HD) have been reported to have decreased levels of ω-3 polyunsaturated fatty acids (PUFAs) in plasma and cells. The aim of this study was to investigate the effect of ω-3 PUFAs administered intravenously during HD, as well as the effect of HD treatment, on the fatty acid composition of plasma free fatty acids (FFAs), plasma phospholipids, and platelet phospholipids. Forty-four HD patients were randomized to groups receiving either a single dose of a lipid emulsion containing 4.1 g of ω-3 PUFAs or placebo (saline) administered intravenously during HD. Blood was drawn immediately before (baseline) and after (4 hours) HD and before the next HD session (48 hours). Fatty acid composition was measured using gas chromatography. The increase in ω-3 FFAs was greater in the ω-3 PUFA group compared with the placebo group, whereas the increase in total FFAs was similar between the 2 groups. In the ω-3 PUFA group, ω-3 PUFAs in plasma phospholipids were higher after 48 hours than at baseline, and in platelet phospholipids, ω-3 PUFAs increased after 4 hours. In the placebo group, no changes were observed in ω-3 PUFAs in plasma and platelet phospholipids. Intravenous ω-3 PUFAs administered during HD caused a transient selective increase in ω-3 FFA concentration. Furthermore, ω-3 PUFAs were rapidly incorporated into platelets, and the content of ω-3 PUFAs in plasma phospholipids increased after 48 hours.

Lecithin has no effect on serum lipoprotein, plasma fibrinogen and macro molecular protein complex levels in hyperlipidaemic men in a double-blind controlled study.

PubMed

Oosthuizen, W; Vorster, H H; Vermaak, W J; Smuts, C M; Jerling, J C; Veldman, F J; Burger, H M

1998-06-01

To examine the effects of lecithin on serum lipoprotein, plasma fibrinogen and macro molecular protein complex (MPC) levels. Twenty free living hyperlipidaemic men participated in this double-blind study which controlled for possible indirect effects. The subjects were randomly assigned to one of three treatments: frozen yoghurt or frozen yoghurt with 20 g soya bean lecithin or frozen yoghurt with 17 g sunflower oil. Sunflower oil was used to control for the increased energy and linoleic acid intake from lecithin. Yoghurt served as the 'vehicle' for the lecithin and sunflower oil and yoghurt alone was given to one group to control for possible effects due to the yoghurt 'vehicle', as well as other environmental influences. Variables were measured with standard methods twice at baseline and after 2 and 4 weeks of treatment. Plasma linoleic acid levels increased significantly with lecithin and sunflower oil treatments indicating that compliance to the treatments were obtained. Lecithin treatment did not have significant effects on serum total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, apolipoprotein A, apolipoprotein B or lipoprotein (a) levels. Plasma fibrinogen and MPC levels were also not affected by lecithin therapy. Sunflower oil treatment resulted in significant increased body weight, serum TC and decreased MPC levels. Lecithin treatment had no independent effects on serum lipoprotein, plasma fibrinogen or MPC levels in hyperlipidaemic men.

Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

PubMed

Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

2006-05-01

Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (P<.05) as compared with control adult offspring (6.04+/-2.28 vs 10.33+/-0.86 g/100 g fatty acids) and higher n-6/n-3 ratio (P<.05). Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.

Relationship between red cell membrane fatty acids and adipokines in individuals with varying insulin sensitivity.

PubMed

Min, Y; Lowy, C; Islam, S; Khan, F S; Swaminathan, R

2011-06-01

Plasma leptin and adiponectin, and membrane phospholipid fatty acid composition are implicated into the mechanism of insulin resistance but no clear pattern has emerged. Hence, this study examined these variables in subjects presenting to the diabetic clinic for a diagnostic glucose tolerance test. Body composition, glucose, glycated hemoglobin, insulin, leptin, adiponectin, and red cell and plasma phospholipid fatty acids were assessed from 42 normal and 28 impaired glucose tolerant subjects. Insulin sensitivity was determined by homeostatic model assessment. The plasma phosphatidylcholine fatty acid composition of the impaired glucose tolerant subjects was similar to that of normal subjects. However, the impaired glucose tolerant subjects had significantly lower linoleic (P<0.05), eicosapentaenoic (P<0.05) and docosahexaenoic (P<0.01) acids in the red cell phosphatidylcholine and phosphatidylethanolamine compared with the normal subjects. Moreover, red cell phosphatidylcholine docosahexaenoic acid correlated positively with adiponectin (r=0.290, P<0.05) but negatively with leptin (r=-0.252, P<0.05), insulin (r=-0.335, P<0.01) and insulin resistance (r=-0.322, P<0.01). Plasma triglycerides, leptin and glucose combined predicted about 60% of variation in insulin level whereas insulin was the only component that predicted the membrane fatty acids. We postulate that membrane phospholipids fatty acids have an indirect role in determining insulin concentration but insulin has a major role in determining membrane fatty acid composition.

Effects of feeding omega-3-fatty acids on fatty acid composition and quality of bovine sperm and on antioxidative capacity of bovine seminal plasma.

PubMed

Gürler, Hakan; Calisici, Oguz; Calisici, Duygu; Bollwein, Heinrich

2015-09-01

The aim of the present study was to examine the effects of feeding alpha-linolenic (ALA) acid on fatty acid composition and quality of bovine sperm and on antioxidative capacity of seminal plasma. Nine bulls (ALA bulls) were fed with 800 g rumen-resistant linseed oil with a content of 50% linolenic acid and eight bulls with 400 g palmitic acid (PA bulls). Sperm quality was evaluated for plasma membrane and acrosome intact sperm (PMAI), the amount of membrane lipid peroxidation (LPO), and the percentage of sperm with a high DNA fragmentation index (DFI). Fatty acid content of sperm was determined using gas chromatography. Total antioxidant capacity, glutathione peroxidase, and superoxide dismutase activity were determined in seminal plasma. Feeding ALA increased (P < 0.05) the docosahexaenoic acid (DHA) content in bulls whereas in PA bulls did not change. PMAI increased after cryopreservation in ALA bulls as well as in PA bulls during the experiment period (P < 0.005). LPO of sperm directly after thawing did not change during the study period in ALA group, but decreased in PA group (P < 0.006). After 3h of incubation LPO increased in the ALA group (P < 0.02), while LPO did not differ between phases within groups. In conclusion, feeding of neither saturated nor polyunsaturated fatty acids affect the antioxidant levels in seminal plasma. Both saturated as well as polyunsaturated fatty acids had positive effects on quality of cryopreserved bovine sperm, although the content of docosahexaenoic acid in sperm membranes increased only in ALA bulls. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of flaxseed oil and microalgae DHA on the production performance, fatty acids and total lipids of egg yolk and plasma in laying hens.

PubMed

Neijat, M; Ojekudo, O; House, J D

2016-12-01

The incorporation of omega-3 polyunsaturated fatty acids (PUFA) in the egg is dependent on both the transfer efficiency of preformed dietary omega-3 fatty acids to the eggs as well as endogenous PUFA metabolism and deposition. Employing an experimental design consisting of 70 Lohmann LSL-Classic hens (n=10/treatment) in a 6-week feeding trial, we examined the impact of graded levels of either flaxseed oil (alpha-linolenic acid, ALA) or algal DHA (preformed docosahexaenoic acid, DHA), each supplying 0.20%, 0.40% and 0.60% total omega-3s. The control diet was practically low in omega-3s. Study parameters included monitoring the changes of fatty acid contents in yolk, measures of hen performance, eggshell quality, total lipids and fatty acid contents of plasma. Data were analysed as a complete randomized design using Proc Mixed procedure of SAS. No significant differences were observed between treatments with respect to hen performance, eggshell quality and cholesterol content in plasma and egg yolk. Individual and total omega-3 PUFA in the yolk and plasma increased (P<0.0001) linearly as a function of total omega-3 PUFA intake. At the highest inclusion levels, DHA-fed hens incorporated 3-fold more DHA in eggs compared with ALA-fed hens (179±5.55 vs. 66.7±2.25mg/yolk, respectively). In both treatment groups, maximal enrichment of total n-3 PUFA was observed by week-2, declined by week-4 and leveled thereafter. In addition, accumulation of DHA in egg yolk showed linear (P<0.0001) and quadratic (P<0.05) effects for flaxseed oil (R 2 =0.89) and algal DHA (R 2 =0.95). The current data, based on defined level of total omega-3s in the background diet, provides evidence to suggest that exogenous as well as endogenous synthesis of DHA may be subject to a similar basis of regulation, and serve to highlight potential regulatory aspects explaining the limitations in the deposition of endogenously produced omega-3 LCPUFA. Copyright © 2016 Elsevier Ltd. All rights reserved.

GABA and homovanillic acid in the plasma of Schizophrenic and bipolar I patients.

PubMed

Arrúe, Aurora; Dávila, Ricardo; Zumárraga, Mercedes; Basterreche, Nieves; González-Torres, Miguel A; Goienetxea, Biotza; Zamalloa, Maria I; Anguiano, Juan B; Guimón, José

2010-02-01

We have determined the plasma (p) concentration of gamma-aminobutyric acid (GABA) and the dopamine metabolite homovanillic acid (HVA), and the pHVA/pGABA ratio in schizophrenic and bipolar patients. The research was undertaken in a geographic area with an ethnically homogeneous population. The HVA plasma concentrations were significantly elevated in the schizophrenic patients compared to the bipolar patients. The levels of pGABA was significantly lower in the two groups of patients compared to the control group, while the pHVA/pGABA ratio was significantly greater in the both groups of patients compared to the controls. As the levels of pHVA and pGABA are partially under genetic control it is better to compare their concentrations within an homogeneous population. The values of the ratio pHVA/pGABA are compatible with the idea of an abnormal dopamine-GABA interaction in schizophrenic and bipolar patients. The pHVA/pGABA ratio may be a good peripheral marker in psychiatric research.

Effects of B Vitamins Overload on Plasma Insulin Level and Hydrogen Peroxide Generation in Rats.

PubMed

Sun, Wuping; Zhai, Mingzhu; Zhou, Qian; Qian, Chengrui; Jiang, Changyu

2017-08-31

It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H₂O₂ levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H₂O₂ generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.

Temporal trends of perfluoroalkyl acids in plasma samples of pregnant women in Hokkaido, Japan, 2003-2011.

PubMed

Okada, Emiko; Kashino, Ikuko; Matsuura, Hideyuki; Sasaki, Seiko; Miyashita, Chihiro; Yamamoto, Jun; Ikeno, Tamiko; Ito, Yoichi M; Matsumura, Toru; Tamakoshi, Akiko; Kishi, Reiko

2013-10-01

Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that are used in a wide range of consumer products. Recent epidemiological studies have shown that prenatal exposure to toxic levels of PFAAs in the environment may adversely affect fetal growth and humoral immune response in infants and children. Here we have characterized levels of prenatal exposure to PFAA between 2003 and 2011 in Hokkaido, Japan, by measuring PFAA concentrations in plasma samples from pregnant women. The study population comprised 150 women who enrolled in a prospective birth cohort study conducted in Hokkaido. Eleven PFAAs were measured in maternal plasma samples using simultaneous analysis by ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. At the end of the study, in 2011, age- and parity-adjusted mean concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were 1.35ng/mL, 1.26ng/mL, 0.66ng/mL, 1.29ng/mL, 0.25ng/mL, 0.33ng/mL, 0.28ng/mL, and 3.86ng/mL, respectively. Whereas PFOS and PFOA concentrations declined 8.4%/y and 3.1%/y, respectively, PFNA and PFDA levels increased 4.7%/y and 2.4%/y, respectively, between 2003 and 2011. PFUnDA, PFDoDA, and PFTrDA were detected in the vast majority of maternal samples, but no significant temporal trend was apparent. Future studies must involve a larger population of pregnant women and their children to determine the effects of prenatal exposure to PFAA on health outcomes in infants and children. © 2013.

The effect of testosterone on cardiometabolic risk factors in atorvastatin-treated men with late-onset hypogonadism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Okopień, Bogusław

2016-02-01

By reducing LDL cholesterol levels, statins may decrease androgen production. This study was aimed at investigating whether testosterone treatment has an impact on cardiometabolic risk factors in statin-treated men with late-onset hypogonadism (LOH). The study included 31 men with LOH who had been treated for at least 6 months with atorvastatin (20-40mg daily). On the basis of patient preference, atorvastatin-treated patients were divided into two matched groups of patients: receiving intramuscular testosterone enanthate (100mg weekly, n=16) and not treated with this hormone (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were assessed before and after 4 months of therapy. Compared with the control age-, weight, and lipid-matched statin-naïve subjects with LOH (n=12), atorvastatin-treated patients were characterized by decreased levels of testosterone, hsCRP, and homocysteine. In patients not receiving testosterone therapy, plasma lipids, glucose homeostasis markers, as well as plasma levels of the investigated risk factors remained at the similar levels throughout the whole period of atorvastatin treatment. In atorvastatin-naïve patients, testosterone increased its plasma levels and decreased HDL cholesterol. Apart from an increase in testosterone levels, if administered to atorvastatin-treated subjects with LOH, testosterone reduced plasma levels of LDL cholesterol, uric acid, hsCRP, homocysteine, and fibrinogen, as well as improved insulin sensitivity. Our study may suggest the clinical benefits associated with combination therapy with a statin and testosterone in elderly men with LOH. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Falsely Elevated Plasma Creatinine Due to an Immunoglobulin M Paraprotein.

PubMed

McGill, Mitchell R; Vijayan, Anitha; Trulock, Elbert P; Witt, Chad A; Kohler, Giselle D; Scott, Mitchell G

2016-11-01

The most common method for measuring plasma creatinine is based on its reaction with picric acid. However, enzymatic methods are becoming more popular due to improved specificity. We present a case of falsely elevated plasma creatinine values obtained by an enzymatic method that turned out to be due to a monoclonal immunoglobulin M (IgM) paraprotein. A 63-year-old woman evaluated for lung transplantation had falsely increased plasma creatinine levels (1.54-1.71mg/dL; corresponding to estimated glomerular filtration rates of 32-36 mL/min/1.73m 2 ) as measured by the Roche Creatinine plus enzymatic assay when compared with the picric acid-based procedure and several other enzymatic methods, which gave plasma creatinine values of 0.7 to 0.8mg/dL. Serum protein electrophoresis revealed an IgM κ light chain paraprotein. Removal of high-molecular-weight (>30kDa) proteins by ultrafiltration reduced the patient's plasma creatinine level by the Roche enzymatic method to 0.7mg/dL. Addition of the patient's immunoglobulin fraction to plasma from other patients with normal plasma creatinine levels resulted in values that were increased by 0.58 to 0.62mg/dL. Furthermore, removal of non-IgM immunoglobulins with protein G-coupled beads did not eliminate the interference from the patient's plasma. Taken together, these studies demonstrate that falsely elevated plasma creatinine values by the Roche enzymatic method can be due to an IgM paraprotein. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Reduced protein oxidation in Wistar rats supplemented with marine ω3 PUFAs.

PubMed

Méndez, Lucía; Pazos, Manuel; Gallardo, José M; Torres, Josep L; Pérez-Jiménez, Jara; Nogués, Rosa; Romeu, Marta; Medina, Isabel

2013-02-01

The potential effects of various dietary eicosapentaenoic acid (EPA; 20:5) and docosahexaenoic acid (DHA; 22:6) ratios (1:1, 2:1, and 1:2, respectively) on protein redox states from plasma, kidney, skeletal muscle, and liver were investigated in Wistar rats. Dietary fish oil groups were compared with animals fed soybean and linseed oils, vegetable oils enriched in ω6 linoleic acid (LA; 18:2) and ω3 α-linolenic acid (ALA; 18:3), respectively. Fish oil treatments were effective at reducing the level of total fatty acids in plasma and enriching the plasmatic free fatty acid fraction and erythrocyte membranes in EPA and DHA. A proteomic approach consisting of fluorescein 5-thiosemicarbazide (FTSC) labeling of protein carbonyls, FTSC intensity visualization on 1-DE or 2-DE gels, and protein identification by MS/MS was used for the protein oxidation assessment. Albumin was found to be the most carbonylated protein in plasma for all dietary groups, and its oxidation level was significantly modulated by dietary interventions. Supplementation with an equal EPA:DHA ratio (1:1) showed the lowest oxidation score for plasma albumin, followed in increasing order of carbonylation by 1:2 <2:1 ≈ linseed < soybean. Oxidation patterns of myofibrillar skeletal muscle proteins and cytosolic proteins from kidney and liver also indicated a protective effect on proteins for the fish oil treatments, the 1:1 ratio exhibiting the lowest protein oxidation scores. The effect of fish oil treatments at reducing carbonylation on specific proteins from plasma (albumin), skeletal muscle (actin), and liver (albumin, argininosuccinate synthetase, 3-α-hydroxysteroid dehydrogenase) was remarkable. This investigation highlights the efficiency of dietary fish oil at reducing in vivo oxidative damage of proteins compared to oils enriched in the 18-carbon polyunsaturated fatty acids ω3 ALA and ω6 LA, and such antioxidant activity may differ among different fish oil sources because of variations in EPA/DHA content. Copyright © 2012 Elsevier Inc. All rights reserved.

Postprandial lipid responses to an alpha-linolenic acid-rich oil, olive oil and butter in women: a randomized crossover trial.

PubMed

Svensson, Julia; Rosenquist, Anna; Ohlsson, Lena

2011-06-28

Postprandial lipaemia varies with gender and the composition of dietary fat due to the partitioning of fatty acids between beta-oxidation and incorporation into triacylglycerols (TAGs). Increasing evidence highlights the importance of postprandial measurements to evaluate atherogenic risk. Postprandial effects of alpha-linolenic acid (ALA) in women are poorly characterized. We therefore studied the postprandial lipid response of women to an ALA-rich oil in comparison with olive oil and butter, and characterized the fatty acid composition of total lipids, TAGs, and non-esterified fatty acids (NEFAs) in plasma. A randomized crossover design (n = 19) was used to compare the postprandial effects of 3 meals containing 35 g fat. Blood samples were collected at regular intervals for 7 h. Statistical analysis was carried out with ANOVA (significant difference = P < 0.05). No significant difference was seen in incremental area under the curve (iAUC) plasma-TAG between the meals. ALA and oleic acid levels were significantly increased in plasma after ALA-rich oil and olive oil meals, respectively. Palmitic acid was significantly increased in plasma-TAG after the butter meal. The ratios of 18:2 n-6 to18:3 n-3 in plasma-TAGs, three and seven hours after the ALA-rich oil meal, were 1.5 and 2.4, respectively. The corresponding values after the olive oil meal were: 13.8 and 16.9; and after the butter meal: 9.0 and 11.6. The postprandial p-TAG and NEFA response in healthy pre-menopausal women was not significantly different after the intake of an ALA-rich oil, olive oil and butter. The ALA-rich oil significantly affected different plasma lipid fractions and improved the ratio of n-6 to n-3 fatty acids several hours postprandially.

Catecholaminergic effects of prolonged head-down bed rest

NASA Technical Reports Server (NTRS)

Goldstein, D. S.; Vernikos, J.; Holmes, C.; Convertino, V. A.

1995-01-01

Prolonged head-down bed rest (HDBR) provides a model for examining responses to chronic weightlessness in humans. Eight healthy volunteers underwent HDBR for 2 wk. Antecubital venous blood was sampled for plasma levels of catechols [norepinephrine (NE), epinephrine, dopamine, dihydroxyphenylalanine, dihydroxyphenylglycol, and dihydroxyphenylacetic acid] after supine rest on a control (C) day and after 4 h and 7 and 14 days of HDBR. Urine was collected after 2 h of supine rest during day C, 2 h before HDBR, and during the intervals 1-4, 4-24, 144-168 (day 7), and 312-336 h (day 14) of HDBR. All subjects had decreased plasma and blood volumes (mean 16%), atriopeptin levels (31%), and peripheral venous pressure (26%) after HDBR. NE excretion on day 14 of HDBR was decreased by 35% from that on day C, without further trends as HDBR continued, whereas plasma levels were only variably and nonsignificantly decreased. Excretion rates of dihydroxyphenylglycol and dihydroxyphenylalanine decreased slightly during HDBR; excretion rates of epinephrine, dopamine, and dihydroxyphenylacetic acid and plasma levels of catechols were unchanged. The results suggest that HDBR produces sustained inhibition of sympathoneural release, turnover, and synthesis of NE without affecting adrenomedullary secretion or renal dopamine production. Concurrent hypovolemia probably interferes with detection of sympathoinhibition by plasma levels of NE and other catechols in this setting. Sympathoinhibition, despite decreased blood volume, may help to explain orthostatic intolerance in astronauts returning from spaceflights.

Effects of dietary polyunsaturated fatty acids and nucleotides on tissue fatty acid profiles of rats with carbon tetrachloride-induced liver damage.

PubMed

Fontana, L; Moreira, E; Torres, M I; Periago, J L; Sánchez de Medina, F; Gil, A

1999-04-01

The deficiency of polyunsaturated fatty acids (PUFA) that occurs in plasma of patients with liver cirrhosis has been assessed in rats with severe steatosis and mild liver necrosis induced by repeated administration of low doses of carbon tetrachloride (CCl(4)). The contribution of both dietary (n-3) long-chain PUFA and nucleotides to the recovery of the altered fatty acid profiles of tissue lipids of these rats has also been studied. Two groups of rats were used. The first was intraperitoneally injected 0.15 ml of a 10% (v/v) CCl(4)solution in paraffin per 100 g of body weight, three times a week for 9 weeks; the second received paraffin alone. After the treatment, six rats of each group were killed. Afterwards, the remaining controls were fed a semipurified diet (SPD) for 3 weeks, and the remaining rats in the CCl(4)group were divided into three new groups: the first was fed the SP diet; the second was fed the SP diet supplemented with 1% (n-3) polyunsaturated fatty acids (PUFA diet); and the third was fed the SP diet supplemented with 250 mg nucleotides per 100 g diet (NT diet). Fatty acids of plasma, erythrocyte membranes and liver microsomes were analyzed. Decreases in linoleic and arachidonic acids in both total plasma lipids and liver microsomal phospholipids were the main findings due to CCl(4)treatment. The rats that received CCl(4)and the PUFA diet showed the lowest levels of (n-6) PUFA and the highest levels of (n-3) PUFA in liver microsomal phospholipids, as well as a significant increase of (n-3) PUFAs in total plasma lipids. The animals that received the NT diet showed no signs of fatty infiltration and exhibited the highest levels of (n-6) PUFAs in liver microsomal phospholipids. These results show that CCl(4)affects fatty acid metabolism which is accordingly reflected in altered tissue fatty acid profiles, and that balanced diets containing PUFA and nucleotides are important for the recovery of the damaged liver in rats. Copyright 1999 Harcourt Publishers Ltd.

Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

PubMed

Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

2016-10-01

Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P < 0.01) whole body phenylalanine rate of appearance (μmol·kg -1 ·min -1 ), indicating suppression of muscle proteolysis, in both the control (1.02 ± 0.04 vs 0.76 ± 0.04) and the BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. Copyright © 2016 the American Physiological Society.

Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans

PubMed Central

Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C.; Dedmon, William L.

2016-01-01

Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P < 0.01) whole body phenylalanine rate of appearance (μmol·kg−1·min−1), indicating suppression of muscle proteolysis, in both the control (1.02 ± 0.04 vs 0.76 ± 0.04) and the BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. PMID:27530230

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats.

PubMed

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography-tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney.

Chronic Arachidonic Acid Administration Decreases Docosahexaenoic Acid- and Eicosapentaenoic Acid-Derived Metabolites in Kidneys of Aged Rats

PubMed Central

Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Mamun, Abdullah Al; Tanabe, Yoko; Arita, Makoto; Shido, Osamu

2015-01-01

Arachidonic acid (ARA) metabolites produced by cyclo-oxygenase and lipoxygenase are important mediators maintaining physiological renal function. However, the effects of exogenous ARA on kidney function in vivo remain unknown. This study examined the effects of long-term oral ARA administration on normal renal function as well as inflammation and oxidative stress in aged rats. In addition, we measured levels of renal eicosanoids and docosanoids using liquid chromatography–tandem mass spectrometry. Control or ARA oil (240 mg/kg body weight/day) was orally administered to 21-month-old Wistar rats for 13 weeks. Levels of plasma creatinine, blood urea nitrogen, inflammatory and anti-inflammatory cytokines, reactive oxygen species, and lipid peroxidation were not significantly different between the two groups. The ARA concentration in the plasma, kidney, and liver increased in the ARA-administered group. In addition, levels of free-form ARA, prostaglandin E2, and 12- and 15-hydroxyeicosatetraenoic acid increased in the ARA-administered group, whereas renal concentration of docosahexaenoic acid and eicosapentaenoic acid decreased in the ARA-administered group. Levels of docosahexaenoic acid-derived protectin D1, eicosapentaenoic acid-derived 5-, and 18-hydroxyeicosapentaenoic acids, and resolvin E2 and E3 decreased in the ARA-administered group. Our results indicate that long-term ARA administration led to no serious adverse reactions under normal conditions and to a decrease in anti-inflammatory docosahexaenoic acid- and eicosapentaenoic acid-derived metabolites in the kidneys of aged rats. These results indicate that there is a possibility of ARA administration having a reducing anti-inflammatory effect on the kidney. PMID:26485038

Dietary Caprylic Acid (C8:0) Does Not Increase Plasma Acylated Ghrelin but Decreases Plasma Unacylated Ghrelin in the Rat

PubMed Central

Lemarié, Fanny; Beauchamp, Erwan; Dayot, Stéphanie; Duby, Cécile; Legrand, Philippe; Rioux, Vincent

2015-01-01

Focusing on the caprylic acid (C8:0), this study aimed at investigating the discrepancy between the formerly described beneficial effects of dietary medium chain fatty acids on body weight loss and the C8:0 newly reported effect on food intake via ghrelin octanoylation. During 6 weeks, Sprague-Dawley male rats were fed with three dietary C8:0 levels (0, 8 and 21% of fatty acids) in three experimental conditions (moderate fat, caloric restriction and high fat). A specific dose-response enrichment of the stomach tissue C8:0 was observed as a function of dietary C8:0, supporting the hypothesis of an early preduodenal hydrolysis of medium chain triglycerides and a direct absorption at the gastric level. However, the octanoylated ghrelin concentration in the plasma was unchanged in spite of the increased C8:0 availability. A reproducible decrease in the plasma concentration of unacylated ghrelin was observed, which was consistent with a decrease in the stomach preproghrelin mRNA and stomach ghrelin expression. The concomitant decrease of the plasma unacylated ghrelin and the stability of its acylated form resulted in a significant increase in the acylated/total ghrelin ratio which had no effect on body weight gain or total dietary consumption. This enhanced ratio measured in rats consuming C8:0 was however suspected to increase (i) growth hormone (GH) secretion as an increase in the GH-dependent mRNA expression of the insulin like growth Factor 1 (IGF-1) was measured (ii) adipocyte diameters in subcutaneous adipose tissue without an increase in the fat pad mass. Altogether, these results show that daily feeding with diets containing C8:0 increased the C8:0 level in the stomach more than all the other tissues, affecting the acylated/total ghrelin plasma ratio by decreasing the concentration of circulating unacylated ghrelin. However, these modifications were not associated with increased body weight or food consumption. PMID:26196391

Differential distribution of proteins and lipids in detergent-resistant and detergent-soluble domains in rod outer segment plasma membranes and disks.

PubMed

Elliott, Michael H; Nash, Zack A; Takemori, Nobuaki; Fliesler, Steven J; McClellan, Mark E; Naash, Muna I

2008-01-01

Membrane heterogeneity plays a significant role in regulating signal transduction and other cellular activities. We examined the protein and lipid components associated with the detergent-resistant membrane (DRM) fractions from retinal rod outer segment (ROS) disk and plasma membrane-enriched preparations. Proteomics and correlative western blot analysis revealed the presence of alpha and beta subunits of the rod cGMP-gated ion channel and glucose transporter type 1, among other proteins. The glucose transporter was present exclusively in ROS plasma membrane (not disks) and was highly enriched in DRMs, as was the cGMP-gated channel beta-subunit. In contrast, the majority of rod opsin and ATP-binding cassette transporter A4 was localized to detergent-soluble domains in disks. As expected, the cholesterol : fatty acid mole ratio was higher in DRMs than in the corresponding parent membranes (disk and plasma membranes, respectively) and was also higher in disks compared to plasma membranes. Furthermore, the ratio of saturated : polyunsaturated fatty acids was also higher in DRMs compared to their respective parent membranes (disk and plasma membranes). These results confirm that DRMs prepared from both disks and plasma membranes are enriched in cholesterol and in saturated fatty acids compared to their parent membranes. The dominant fatty acids in DRMs were 16 : 0 and 18 : 0; 22 : 6n3 and 18 : 1 levels were threefold higher and twofold lower, respectively, in disk-derived DRMs compared to plasma membrane-derived DRMs. We estimate, based on fatty acid recovery that DRMs account for only approximately 8% of disks and approximately 12% of ROS plasma membrane.

The influence of feeding and fasting on plasma metabolites in the dogfish shark (Squalus acanthias).

PubMed

Wood, Chris M; Walsh, Patrick J; Kajimura, Makiko; McClelland, Grant B; Chew, Shit F

2010-04-01

Dogfish sharks are opportunistic predators, eating large meals at irregular intervals. Here we present a synthesis of data from several previous studies on responses in plasma metabolites after natural feeding and during prolonged fasting (up to 56days), together with new data on changes in plasma concentrations of amino acids and non-esterified fatty acids. Post-prandial and long-term fasting responses were compared to control sharks fasted for 7days, a typical inter-meal interval. A feeding frenzy was created in which dogfish were allowed to feed naturally on dead teleosts at two consumed ration levels, 2.6% and 5.5% of body weight. Most responses were more pronounced at the higher ration level. These included increases in urea and TMAO concentrations at 20h, followed by stability through to 56days of fasting. Ammonia levels were low and exhibited little short-term response to feeding, but declined to very low values during the extended fast. Glucose and beta-hydroxybutyrate both fell after feeding, the latter to a greater and more prolonged extent (up to 60h), whereas acetoacetate did not change. During prolonged fasting, glucose concentrations were well regulated, but beta-hydroxybutyrate increased to 2-3-fold control levels. Total plasma amino acid concentrations increased in a biphasic fashion, with peaks at 6-20h, and 48-60h after the meal, followed by homeostasis during the extended fast. Essential and non-essential amino acids generally followed this same pattern, though some exhibited different trends after feeding: taurine, beta-alanine, and glycine (decreases or stability), alanine and glutamine (modest prolonged increases), and threonine, serine, asparagine, and valine (much larger short-term increases). Plasma non-esterified fatty acid concentrations declined markedly through 48h after the 2.6% meal. These data are interpreted in light of companion studies showing elevations in aerobic metabolic rate, urea production, rectal gland function, metabolic base excretion, and activation of ornithine-urea cycle and aerobic enzymes after the meal, and muscle N-depletion but maintenance of osmolality and urea production during long-term fasting.

Urinary and plasma purine derivatives in fed and fasted llamas (Lama glama and L. guanacoe).

PubMed

Bakker, M L; Chen, X B; Kyle, D J; Orskov, E R; Bourke, D A

1996-02-01

The changes in urinary and plasma purine derivatives in response to fasting and level of feeding in llamas were examines. In one experiment, four llamas were gradually deprived of feed within 3 days and then fasted for 6 days. Daily urinary excretion of purine derivatives decreased with feed intake and leveled on the last 3 days of fasting at 177 +/- 26 mumol/kg W0.75. Allantoin and uric acid comprised 71% and 15% of total purine derivatives, respectively, in both fed and fasted states, but hypoxanthine plus xanthine increased from 9% to 36%. Plasma concentration of allantoin declined with feed intake reduction, but those of uric acid (217 mumol/l) and hypoxanthine plus xanthine (27 mumol/l) remained relatively unchanged. Concentration of uric acid was higher than that of allantoin, probably due to a high reabsorption of uric acid in renal tubules, which was measured as over 90%. In a second experiment, the four llamas were fed at 860 and 1740 g dry matter/d in a crossover design. Urinary total purine derivatives excretion responded to feed intake (10.4 vs 14.4 mmol/d), although the observed differences did not reach significance. Compared with some ruminant species, it appears that the llama resembles sheep regarding the magnitude of urinary purine derivatives excretion but is unique in maintaining a high concentration of uric acid in plasma, which could be part of the llama's adaptation to their environment.

Voluntary wheel running is beneficial to the amino acid profile of lysine-deficient rats.

PubMed

Nagao, Kenji; Bannai, Makoto; Seki, Shinobu; Kawai, Nobuhiro; Mori, Masato; Takahashi, Michio

2010-06-01

Rats voluntarily run up to a dozen kilometers per night when their cages are equipped with a running wheel. Daily voluntary running is generally thought to enhance protein turnover. Thus, we sought to determine whether running worsens or improves protein degradation caused by a lysine-deficient diet and whether it changes the utilization of free amino acids released by proteolysis. Rats were fed a lysine-deficient diet and were given free access to a running wheel or remained sedentary (control) for 4 wk. Amino acid levels in plasma, muscle, and liver were measured together with plasma insulin levels and tissue weight. The lysine-deficient diet induced anorexia, skeletal muscle loss, and serine and threonine aminoacidemia, and it depleted plasma insulin and essential amino acids in skeletal muscle. Allowing rats to run voluntarily improved these symptoms; thus, voluntary wheel running made the rats less susceptible to dietary lysine deficiency. Amelioration of the declines in muscular leucine and plasma insulin observed in running rats could contribute to protein synthesis together with the enhanced availability of lysine and other essential amino acids in skeletal muscle. These results indicate that voluntary wheel running under lysine-deficient conditions does not enhance protein catabolism; on the contrary, it accelerates protein synthesis and contributes to the maintenance of muscle mass. The intense nocturnal voluntary running that characterizes rodents might be an adaptation of lysine-deficient grain eaters that allows them to maximize opportunities for food acquisition.

Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium

PubMed Central

Kabagambe, Edmond K.; Nettleton, Jennifer A.; King, Irena B.; Weng, Lu-Chen; Bhattacharya, Sayanti; Bandinelli, Stefania; Bis, Joshua C.; Rich, Stephen S.; Jacobs, David R.; Cherubini, Antonio; McKnight, Barbara; Liang, Shuang; Gu, Xiangjun; Rice, Kenneth; Laurie, Cathy C.; Lumley, Thomas; Browning, Brian L.; Psaty, Bruce M.; Chen, Yii-Der I.; Friedlander, Yechiel; Djousse, Luc; Wu, Jason H. Y.; Siscovick, David S.; Uitterlinden, André G.; Arnett, Donna K.; Ferrucci, Luigi; Fornage, Myriam; Tsai, Michael Y.; Mozaffarian, Dariush; Steffen, Lyn M.

2011-01-01

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3×10−64) and lower levels of eicosapentaenoic acid (EPA, p = 5×10−58) and docosapentaenoic acid (DPA, p = 4×10−154). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2×10−12) and DPA (p = 1×10−43) and lower docosahexaenoic acid (DHA, p = 1×10−15). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1×10−8). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries. PMID:21829377

Effects of different ratios of monounsaturated and polyunsaturated fatty acids to saturated fatty acids on regulating body fat deposition in hamsters.

PubMed

Liao, Fang-Hsuean; Liou, Tsan-Hon; Shieh, Ming-Jer; Chien, Yi-Wen

2010-01-01

Effects of monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid consumption on regulating body fat accumulation and body weight gain are controversial between animal and human studies. We designed a 2 x 2 factorial study, with two levels of MUFAs (60% and 30%) and two levels of polyunsaturated-to-saturated fatty acid (P/S) ratio (5 and 3) to prepare four kinds of experimental oils consisting of 60% MUFAs with a high or low P/S ratio (HMHR or HMLR, respectively) or 30% MUFAs with a high or low P/S ratio (LMHR or LMLR, respectively). Thirty-two male golden Syrian hamsters were randomly divided into four groups and fed the experimental diets containing 15% (w/w) fat for 12 wk. No difference was observed in the mean daily food intake. Hamsters fed the LMLR diet had increased weight gain, epididymal and retroperitoneal white adipose tissues, plasma non-esterified fatty acids, insulin, hepatic acetyl coenzyme A carboxylase and malic enzyme activities, and mRNA expressions of peroxisome proliferator-activated receptor-alpha and sterol regulatory element-binding protein-1c among all groups (P < 0.05). Hamsters fed the HMHR diet had lower plasma insulin levels and hepatic acetyl coenzyme A carboxylase activities among groups (P < 0.05) and elevated hepatic acyl coenzyme A oxidase and carnitine palmitoyltransferase-I activities compared with those fed the LMLR diet (P < 0.05). Hamsters fed the LMLR diet had increased weight gain and body fat accumulation, whereas the HMHR diet appeared to be beneficial in preventing white adipose tissue accumulation by decreasing plasma insulin levels and increasing hepatic lipolytic enzyme activities involved in beta-oxidation. 2010 Elsevier Inc. All rights reserved.

Increased plasma levels of competing amino acids, rather than lowered plasma tryptophan levels, are associated with a non-response to treatment in major depression.

PubMed

Ormstad, Heidi; Dahl, Johan; Verkerk, Robert; Andreassen, Ole A; Maes, Michael

2016-08-01

Lowered plasma tryptophan (TRP) and TRP/competing amino acid (CAA) ratio may be involved in the pathophysiology of major depression (MDD). Increased cortisol and immune-inflammatory mediators in MDD may affect the availability of TRP to the brain. We investigated whether baseline or post-treatment TRP, CAAs and TRP/CAA ratio are associated with a treatment response in MDD and whether these effects may be mediated by cortisol or immune biomarkers. We included 50 medication-free MDD patients with a depressive episode (DSM diagnosis) and assessed symptom severity with the Inventory of Depressive Symptomatology (IDS) before and after treatment as usual for 12 weeks (endpoint). Plasma levels of TRP, CAAs, the ratio, cortisol, CRP and 6 selected cytokines were assayed. The primary outcome was a 50% reduction in the IDS, while the secondary was a remission of the depressive episode. In IDS non-responders, CAAs increased and the TRP/CAA ratio decreased, while in IDS responders CAAs decreased and the TRP/CAA ratio increased from baseline to endpoint. In patients who were still depressed at endpoint TRP and CAAs levels had increased from baseline, while in remitted patients no such effects were found. Increases in CAAs were inversely correlated with changes in interleukin-1 receptor antagonist levels. The results show that increased CAA levels from baseline to endpoint are associated with a non-response to treatment in MDD patients. This suggests that the mechanism underpinning the CAA-related treatment resistance may be related to changes in immune pathways. CAA levels and amino acid metabolism may be new drug targets in depression. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Long-term dietary supplementation with saury oil attenuates metabolic abnormalities in mice fed a high-fat diet: combined beneficial effect of omega-3 fatty acids and long-chain monounsaturated fatty acids.

PubMed

Yang, Zhi-Hong; Inoue, Seika; Taniguchi, Yasuko; Miyahara, Hiroko; Iwasaki, Yusuke; Takeo, Jiro; Sakaue, Hiroshi; Nakaya, Yutaka

2015-12-01

Pacific saury is a common dietary component in East Asia. Saury oil contains considerable levels of n-3 unsaturated fatty acids (PUFA) and long-chain monounsaturated fatty acids (LCMUFA) with aliphatic tails longer than 18 carbons. In our previous study, consumption of saury oil for 4 to 6 wk improved insulin sensitivity and the plasma lipid profile in mice. However, the long-term effects of saury oil on metabolic syndrome (MetS) risk factors remain to be demonstrated. In the current study, we examined the long-term effects of saury oil on mice fed a high-fat diet, and compared the effect of n-3 PUFA EPA and LCMUFA on MetS risk factor in diet-induced obese mice. In Experiment 1, male C57BL/6 J mice were fed either a 32% lard diet (control) or a diet containing 22% lard plus 10% saury oil (saury oil group) for 18 weeks. Although no differences were found in body weight and energy expenditure between the control and saury oil groups, the saury oil diet decreased plasma insulin, non-HDL cholesterol, hepatic steatosis, and adipocyte size, and altered levels of mRNA transcribed from genes involved in insulin signaling and inflammation in adipose tissue. Organ and plasma fatty acid profile analysis revealed that consumption of saury oil increased n-3 PUFA and LCMUFA (especially n-11 LCMUFA) levels in multiple organs, and decreased the fatty acid desaturation index (C16:1/C16:0; C18:1/C18:0) in liver and adipose tissue. In Experiment 2, male C57BL/6 J mice were fed a 32% lard diet (control), a diet containing 28% lard plus 4% EPA (EPA group), or a diet containing 20% lard plus 12% LCMUFA concentrate (LCMUFA group) for 8 weeks. EPA or LCMUFA intake increased organ levels of EPA and LCMUFA, respectively. Consumption of EPA reduced plasma lipid levels and hepatic lipid deposition, and decreased the fatty acid desaturation index in liver and adipose tissue. Consumption of LCMUFA decreased plasma non-HDL cholesterol, improved hyperinsulinemia, and decreased the fatty acid desaturation index in adipose tissue. EPA accumulated mainly in liver, and LCMUFA (especially n-11 LCMUFA) accumulated mainly in white adipose tissue, suggesting their possible individual biological effects for improving MetS. Our results suggest that saury oil-mediated improvement of metabolic syndrome in diet-induced obese mice may possibly be due to a combined effect of n-3 PUFA and LCMUFA.

The physiological disposition of the uricosuric-saluretic agent (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196) in the rat, dog, and monkey.

PubMed

Zacchei, A G; Wishousky, T I

1976-01-01

The physiological disposition of a new saluretic-uricosuric agent, (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy)acetic acid (MK-196), was studied in the rat, dog, and monkey. MK-196 was well absorbed and showed minimal metabolism in these species. Peak plasma levels of radioactivity and drug occurred 0.5-2 hr after oral administration at a dose of 2.5 mg/kg. Essentially all of the radioactivity present in the plasma during the first day was intact MK-196. Following a single dose, a long terminal half-life for plasma radioactivity was observed in the dog (approximately 68 hr) and monkey (approximately 105 hr). The chronic administration of MK-196 to dogs resulted in a dose-related plasma profile and showed no tendency to increase or decrease with dosing. However, upon repeated drug administration to monkeys, the plasma levels of drug increased and then decreased, possibly due to hypochloremia and secondary metabolic alkalosis. Fecal excretion was the predominant route of tracer elimination in the dog (approximately 80%) and rat (approximately 94%), whereas the monkey eliminated the majority of the dose (approximately 60%) via the urine. Minimal metabolism was noted in the three lower species; most of the urinary, plasma, and fecal radioactivity was accounted for as intact drug and its glucuronide conjugate. Three minor metabolites, which were present in dog bile, plasma, and urine, were characterized as: (l,7-dichloro-1alpha-hydroxy-2-methyl-2-phenyl-5-indanyloxy)acetic acid, I; (6,7-dichloro-2-(4-hydroxyphenyl)-2-methyl-2-oxo-5-indanyloxy)acetic acid, II; and 2-methyl-2-phenyl-5-hydroxy-6,7-dichloro-1-indanone, III. The monkey urine and plasma also contained small amounts of II.

Ascorbic acid insufficiency induces the severe defect on bone formation via the down-regulation of osteocalcin production

PubMed Central

Kim, Won; Bae, Seyeon; Kim, Hyemin; Kim, Yejin; Choi, Jiwon; Lim, Sun Young; Lee, Hei Jin; Lee, Jihyuk; Choi, Jiyea; Jang, Mirim; Lee, Kyoung Eun; Chung, Sun G.; Hwang, Young-il

2013-01-01

The L-gulono-γ-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo-/- mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo-/- mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo-/- mice, 3-week ascorbic acid-insufficient Gulo-/- mice, and 4-week ascorbic acid-insufficient Gulo-/- mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo-/- mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo-/- mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo-/- mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo-/-. In summary, ascorbic acid insufficiency in Gulo-/- mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels. PMID:24386598

Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children (ALSPAC)

PubMed Central

Lattka, Eva; Koletzko, Berthold; Zeilinger, Sonja; Hibbeln, Joseph R.; Klopp, Norman; Ring, Susan M.; Steer, Colin D.

2012-01-01

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno–fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism. PMID:22877655

Umbilical cord PUFA are determined by maternal and child fatty acid desaturase (FADS) genetic variants in the Avon Longitudinal Study of Parents and Children (ALSPAC).

PubMed

Lattka, Eva; Koletzko, Berthold; Zeilinger, Sonja; Hibbeln, Joseph R; Klopp, Norman; Ring, Susan M; Steer, Colin D

2013-04-14

Fetal supply with long-chain PUFA (LC-PUFA) during pregnancy is important for brain growth and visual and cognitive development and is provided by materno-fetal placental transfer. We recently showed that maternal fatty acid desaturase (FADS) genotypes modulate the amounts of LC-PUFA in maternal blood. Whether FADS genotypes influence the amounts of umbilical cord fatty acids has not been investigated until now. The aim of the present study was to investigate the influence of maternal and child FADS genotypes on the amounts of LC-PUFA in umbilical cord venous plasma as an indicator of fetal fatty acid supply during pregnancy. A total of eleven cord plasma n-6 and n-3 fatty acids were analysed for association with seventeen FADS gene cluster SNP in over 2000 mothers and children from the Avon Longitudinal Study of Parents and Children. In a multivariable analysis, the maternal genotype effect was adjusted for the child genotype and vice versa to estimate which of the two has the stronger influence on cord plasma fatty acids. Both maternal and child FADS genotypes and haplotypes influenced amounts of cord plasma LC-PUFA and fatty acid ratios. Specifically, most analysed maternal SNP were associated with cord plasma levels of the precursor n-6 PUFA, whereas the child genotypes were mainly associated with more highly desaturated n-6 LC-PUFA. This first study on FADS genotypes and cord fatty acids suggests that fetal LC-PUFA status is determined to some extent by fetal fatty acid conversion. Associations of particular haplotypes suggest specific effects of SNP rs498793 and rs968567 on fatty acid metabolism.

Age dependence of plasma phospholipid fatty acid levels: potential role of linoleic acid in the age-associated increase in docosahexaenoic acid and eicosapentaenoic acid concentrations.

PubMed

de Groot, Renate H M; van Boxtel, Martin P J; Schiepers, Olga J G; Hornstra, Gerard; Jolles, Jelle

2009-10-01

Limited information is available with respect to the association between age and the plasma phospholipid fatty acid profile. Therefore we investigated the association between plasma phospholipid fatty acid status and age after correction for sex, smoking, alcohol use, BMI and fish intake. Plasma phospholipid fatty acid composition was measured and information on fish intake and other potential covariates was collected in 234 participants of the Maastricht Aging Study. The participants were healthy individuals of both sexes with an age range between 36 and 88 years. Hierarchical linear regression analyses were applied to study the relationship between age and fatty acid concentrations. After correction for fish consumption and other relevant covariates, a significant positive relationship was observed between age of the subjects and their plasma phospholipid concentrations of DHA (22 : 6n-3, P = 0.006) and EPA (20 : 5n-3; P = 0.001). Age contributed 2.3 and 3.9 % to the amount of explained variance, respectively. The higher n-3 long-chain PUFA status at advanced age was confirmed by lower concentrations of their putative 'shortage marker' Osbond acid (ObA, 22 : 5n-6; P = 0.022 for the relationship with age after correction for covariates and fish intake, R2 0.022). Concentrations of linoleic acid (LA; 18 : 2n-6) were negatively associated with age (P < 0.001; R2 0.061). In conclusion, DHA and EPA concentrations appeared to be higher in older age groups, partly because of a higher fish intake and partly because of another age-associated mechanism, possibly involving the well-known competition with LA.

Blood fatty acid composition of pregnant and nonpregnant Korean women: red cells may act as a reservoir of arachidonic acid and docosahexaenoic acid for utilization by the developing fetus.

PubMed

Ghebremeskel, K; Min, Y; Crawford, M A; Nam, J H; Kim, A; Koo, J N; Suzuki, H

2000-05-01

Relative fatty acid composition of plasma and red blood cell (RBC) choline phosphoglycerides (CPG), and RBC ethanolamine phosphoglycerides (EPG) of pregnant (n = 40) and nonpregnant, nonlactating (n = 40), healthy Korean women was compared. The two groups were of the same ethnic origin and comparable in age and parity. Levels of arachidonic (AA) and docosahexaenoic (DHA) acids were lower (P < 0.05) and palmitic and oleic acids higher (P < 0.0001) in plasma CPG of the pregnant women. Similarly, the RBC CPG and EPG of the pregnant women had lower AA and DHA (P < 0.05) and higher palmitic and oleic acids (P < 0.01). The reduction in DHA and total n-3 fatty acids in plasma CPG of the pregnant women was paralleled by an increase in docosatetraenoic (DTA) and docosapentaenoic (DPA) acids of the n-6 series and in DPA/DTA ratio. In the RBC phospholipids (CPG and EPG) of the pregnant women, DTA and DPA acids of the n-6 series and DPA/DTA ratio did not increase with the decrease of the n-3 metabolites (eicosapentaenoic acid, DPA, and DHA) and total n-3. Since pregnancy was the main identifiable variable between the two groups, the lower levels of AA and DHA in RBC CPG and EPG of the pregnant women suggest that the mothers were mobilizing membrane AA and DHA to meet the high fetal requirement for these nutrients. It may also suggest that RBC play a role as a potential store of AA and DHA and as a vehicle for the transport of these fatty acids from maternal circulation to the placenta to be utilized by the developing fetus.

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

PubMed

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

2009-11-01

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

Sex differences in plasma homovanillic acid levels in schizophrenia and normal controls: relation to neuroleptic resistance.

PubMed

Sumiyoshi, T; Hasegawa, M; Jayathilake, K; Meltzer, H Y

1997-03-01

Plasma homovanillic acid (pHVA) levels were compared in a large number of neuroleptic-resistant and -responsive schizophrenic patients (male/female = 161/46) and normal controls (67/27), and correlated with various measures of psychopathology. Psychopathology was evaluated with the brief psychiatric rating scale, the Schedule for Affective Disorders and Schizophrenia-Change version (SADS-C) and SADS-C Global Assessment Scale, the Scale for Assessment of Negative Symptoms, the Scale for Assessment of Positive Symptoms (SAPS), and the Quality of Life Scale. No significant differences in pHVA levels between neuroleptic-resistant (n = 104) or -responsive (n = 103) schizophrenic patients, and normal controls, were found; however, there was a main effect for sex, due to higher pHVA levels in women than men. There were no diagnosis x gender or age effects on pHVA levels. No significant correlations were observed between psychopathology ratings and baseline pHVA levels, except with the Hallucinations subscale of SAPS in neuroleptic-responsive patients. Neither duration of neuroleptic washout nor plasma prolactin levels correlated with pHVA levels. Further studies on the origin and significance of the gender difference in pHVA are indicated.

Metabolic response to dietary fibre composition in horses.

PubMed

Brøkner, C; Austbø, D; Næsset, J A; Blache, D; Bach Knudsen, K E; Tauson, A H

2016-07-01

The hypothesis for this study was that a higher dietary proportion of soluble fibre would result in stable and constant plasma metabolite and regulatory hormone concentrations. The study was a 4×4 Latin Square design with a sequence of 17 days adaptation to the ration followed by 8 sampling days. The feed rations consisted of only timothy hay (H), hay plus molassed sugar beet pulp combined with either whole oats (OB) or barley (BB) and hay plus a loose chaff-based concentrate (M). Four horses were fitted with permanent caecal cannulas and liquid caecal content was withdrawn manually and blood was drawn from the jugular vein at 0, 3 and 9 h postprandial. The horses were exercised daily at medium level for about 1 h. Samples were analysed for short-chain fatty acids (SCFA) and metabolic traits. Caecal SCFA and propionic acid concentrations increased with increased dietary starch and soluble fibre. The diet highest in soluble fibre (M) resulted in the highest plasma glucose and insulin concentrations in the morning, which then remained stable and constant throughout the day. A strong interaction (P<0.01) between time and diet was measured for plasma urea, glucose, insulin and leptin. The greatest variations in plasma glycaemic and insulinaemic responses were associated with the cereal grain diets (OB and BB). There were indications of a negative energy balance, which was reflected in a significantly higher plasma β-hydroxybutyrate concentration and a numerically higher non-esterified fatty acid concentration. In conclusion, this study found that inclusion of soluble fibre resulted in increased total caecal SCFA and propionic acid concentrations. This consequently resulted in stable and constant plasma glycaemic and insulinaemic responses. Diets with a high content of soluble fibre provided enough energy for horses at medium work level.

Plasma acylcarnitine profiling indicates increased fatty acid oxidation relative to tricarboxylic acid cycle capacity in young, healthy low birth weight men.

PubMed

Ribel-Madsen, Amalie; Ribel-Madsen, Rasmus; Brøns, Charlotte; Newgard, Christopher B; Vaag, Allan A; Hellgren, Lars I

2016-10-01

We hypothesized that an increased, incomplete fatty acid beta-oxidation in mitochondria could be part of the metabolic events leading to insulin resistance and thereby an increased type 2 diabetes risk in low birth weight (LBW) compared with normal birth weight (NBW) individuals. Therefore, we measured fasting plasma levels of 45 acylcarnitine species in 18 LBW and 25 NBW men after an isocaloric control diet and a 5-day high-fat, high-calorie diet. We demonstrated that LBW men had higher C2 and C4-OH levels after the control diet compared with NBW men, indicating an increased fatty acid beta-oxidation relative to the tricarboxylic acid cycle flux. Also, they had higher C6-DC, C10-OH/C8-DC, and total hydroxyl-/dicarboxyl-acylcarnitine levels, which may suggest an increased fatty acid omega-oxidation in the liver. Furthermore, LBW and NBW men decreased several acylcarnitine levels in response to overfeeding, which is likely a result of an upregulation of fatty acid oxidation due to the dietary challenge. Moreover, C10-OH/C8-DC and total hydroxyl-/dicarboxyl-acylcarnitine levels tended to be negatively associated with the serum insulin level, and the total hydroxyl-/dicarboxyl-acylcarnitine level additionally tended to be negatively associated with the hepatic insulin resistance index. This indicates that an increased fatty acid omega-oxidation could be a compensatory mechanism to prevent an accumulation of lipid species that impair insulin signaling. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Nutrient intake and hormonal status of premenopausal vegetarian Seventh-day Adventists and premenopausal nonvegetarians.

PubMed

Shultz, T D; Leklem, J E

1983-01-01

The relationship between dietary nutrients and plasma estrone, estradiol-17 beta, estriol, dehydroepiandrosterone sulfate, and prolactin levels was investigated in 14 premenopausal Seventh-day Adventist vegetarian (SV) women and 9 premenopausal non-Seventh-day Adventist nonvegetarian (NV) women. The SV subjects consumed less fat, especially saturated fat, and used significantly less fried food than the NV subjects. Plasma levels of estrone and estradiol-17 beta in the SV subjects were significantly lower than in the NV subjects. SV estradiol-17 beta and estriol levels were positively correlated with linoleic acid and protein intake, while NV prolactin levels were significantly correlated with intakes of oleic and linoleic acids and total fat. The data suggest that specific dietary nutrients were related to the hormonal milieu of these SV and NV subjects.

Effects of fenfluramine on plasma homovanillic acid in healthy subjects.

PubMed

Hollander, E; Stein, D J; Saoud, J B; DeCaria, C M; Cooper, T B; Islam, M N; Liebowitz, M R; Stanley, M

1992-01-01

The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose l-fenfluramine show increases in striatal levels of the dopamine metabolite homovanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.

Changes in kynurenine pathway metabolism in Parkinson patients with L-DOPA-induced dyskinesia.

PubMed

Havelund, Jesper F; Andersen, Andreas D; Binzer, Michael; Blaabjerg, Morten; Heegaard, Niels H H; Stenager, Egon; Faergeman, Nils J; Gramsbergen, Jan Bert

2017-09-01

L-3,4-Dihydroxyphenylalanine (L-DOPA) is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study, we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls. Parkinson patients (n = 26) were clinically assessed for severity of motor symptoms (UPDRS) and L-DOPA-induced dyskinesia (UDysRS). Plasma and cerebrospinal fluid samples were collected after overnight fasting and 1-2 h after intake of L-DOPA or other anti-Parkinson medication. Metabolites were analyzed in plasma and cerebrospinal fluid of controls (n = 14), Parkinson patients receiving no L-DOPA (n = 8), patients treated with L-DOPA without dyskinesia (n = 8), and patients with L-DOPA-induced dyskinesia (n = 10) using liquid chromatography-mass spectrometry. We observed approximately fourfold increase in the 3-hydroxykynurenine/kynurenic acid ratio in plasma of Parkinson's patients with L-DOPA-induced dyskinesia. Anthranilic acid levels were decreased in plasma and cerebrospinal fluid of this patient group. 5-Hydroxytryptophan levels were twofold increased in all L-DOPA-treated Parkinson's patients. We conclude that a higher 3-hydroxykynurenine/kynurenic acid ratio in plasma may serve as a biomarker for L-DOPA-induced dyskinesia. Longitudinal studies including larger patients cohorts are needed to verify whether the changes observed here may serve as a prognostic marker for L-DOPA-induced dyskinesia. © 2017 International Society for Neurochemistry.

Diacylglycerol-enriched structured lipids containing CLA and capric acid alter body fat mass and lipid metabolism in rats.

PubMed

Kim, Hye-Jin; Lee, Ki-Teak; Lee, Mi-Kyung; Jeon, Seon-Min; Choi, Myung-Sook

2006-01-01

The present study compared the effect of corn oil, diacylglycerol (DG) oil, and DG-enriched structured lipids (SL-DG) produced from corn oil, capric and conjugated linoleic acid on adiposity in rats fed an AIN-76 diet (5% fat) for 6 weeks. The plasma and hepatic lipids, adipose tissue weight, and enzyme activities related to fatty acid metabolism were determined. The weights of the epididymal white adipose tissue (WAT), perirenal WAT, and interscapular WAT were significantly lower in the SL-DG group than in the DG group. Reduction of fat mass in the SL-DG group was related to suppressing fatty acid synthase activities and enhancing beta-oxidation activity in perirenal WAT. The plasma leptin was lower in the SL-DG group than in the DG group, plus a lower plasma TG level was accompanied by an increase in adipocyte LPL activity. Meanwhile the SL-DG supplement lowered the plasma and hepatic cholesterol level. In addition, the hepatic HMG-CoA reductase and ACAT activities were significantly lower in the SL-DG group than in the other groups. The DG-enriched SL used in this study was effective in enhancing triglyceride metabolism in adipose tissue, especially as regards reducing the abdominal fat mass and cholesterol metabolism in the liver. Copyright 2006 S. Karger AG, Basel.

Plasma n-3 and n-6 fatty acids and inflammatory markers in Chinese vegetarians.

PubMed

Yu, Xiaomei; Huang, Tao; Weng, Xiumei; Shou, Tianxing; Wang, Qiang; Zhou, Xiaoqiong; Hu, Qinxin; Li, Duo

2014-09-29

Polyunsaturated fatty acid (PUFA) intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, the relationship between the PUFA and inflammatory factors in the healthy vegetarians were not clear. We aimed to investigate the plasma fatty acids status, and its association with plasma inflammatory factors in Chinese vegetarians and omnivores. A total of 89 male vegetarians and 106 male omnivores were participated the study. Plasma concentrations of inflammatory factors were detected by ELISA, and as standard methods fatty acids were extracted and determined by chromatography. Compared with omnivores, vegetarians have significant higher interleukin-6 (IL-6), plasma n-6 PUFA, n-6/n-3, and 18:3n-3; while they have significant lower leukotriene B4 (LTB4), cyclo-oxygenase-2 (COX2) and prostaglandin E2 (PGE2), 20:5n-3, 22:5n-3, 22:6n-3, and n-3 PUFA. In vegetarians, plasma 20:4n-6 was significant positively related to TNF-α. LTB4 was significantly positively related to plasma 22:6n-3, and negatively associated with n-6 PUFA. Vegetarians have higher plasma n-6 PUFA and IL-6, but lower LTB4, n-3 PUFA, 22:6n-3, COX2 and PGE2 levels. It would seem appropriate for vegetarians to increase their dietary n-3 PUFA, while reduce dietary n-6 PUFA and thus reduce the risk of chronic inflammatory-related diseases.

Omega-3 supplementation during the first 5 years of life and later academic performance: a randomised controlled trial.

PubMed

Brew, B K; Toelle, B G; Webb, K L; Almqvist, C; Marks, G B

2015-04-01

Consumption of oily fish more than once per week has been shown to improve cognitive outcomes in children. However, it is unknown whether similar benefits can be achieved by long-term omega-3 fatty acid supplementation. The objective was to investigate the effect of omega-3 fatty acid supplementation during the first 5 years of life on subsequent academic performance in children by conducting a secondary analysis of the CAPS (Childhood Asthma Prevention Study). A total of 616 infants with a family history of asthma were randomised to receive tuna fish oil (high in long-chain omega-3 fatty acids, active) or Sunola oil (low in omega-3 fatty acids, control) from the time breastfeeding ceased or at the age of 6 months until the age of 5 years. Academic performance was measured by a nationally standardised assessment of literacy and numeracy (National Assessment Program Literacy and Numeracy (NAPLAN)) in school years 3, 5, 7 and 9. Plasma omega-3 fatty acid levels were measured at regular intervals until 8 years of age. Between-group differences in test scores, adjusted for maternal age, birth weight and maternal education, were estimated using mixed-model regression. Among 239 children, there were no significant differences in NAPLAN scores between active and control groups. However, at 8 years, the proportion of omega-3 fatty acid in plasma was positively associated with the NAPLAN score (0.13 s.d. unit increase in score per 1% absolute increase in plasma omega-3 fatty acid (95% CI 0.03, 0.23)). Our findings do not support the practice of supplementing omega-3 fatty acids in the diet of young children to improve academic outcomes. Further exploration is needed to understand the association between plasma omega-3 fatty acid levels at 8 years and academic performance.

Fatty acid supply with complementary foods and LC-PUFA status in healthy infants: results of a randomised controlled trial.

PubMed

Libuda, Lars; Mesch, Christina M; Stimming, Madlen; Demmelmair, Hans; Koletzko, Berthold; Warschburger, Petra; Blanke, Katharina; Reischl, Eva; Kalhoff, Hermann; Kersting, Mathilde

2016-06-01

Introduction of complementary food usually leads to decreasing intakes of long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFA), compared to full breastfeeding. In the randomised controlled PINGU intervention trial, we tested the effects of complementary foods with different contents of alpha-linolenic acid (ALA) and docosahexaenoic acid (DHA) on term infant LC-PUFA status. Healthy infants born at term were randomised to receive from the introduction of complementary feeding at the age of 4 to 6 months until age of 10 months ready-made complementary meals either with ALA-rich rapeseed oil (intervention group (IG)-R), with salmon twice weekly to provide preformed DHA (IG-F), or with linoleic acid-rich corn oil (control group, CG). Fatty acid composition was assessed in erythrocyte (RBC) and plasma glycerophospholipids. Complete data of fatty acids in RBC (plasma) were available from 158 (155) infants. After intervention, infants assigned to IG-F showed higher RBC and plasma percentages of eicosapentaenoic acid (EPA), DHA, and total n-3 LC-PUFA than CG (each p < 0.001). In IG-R, levels of ALA and the ratio of ALA to LA in plasma and RBC (all p < 0.0001) as well as RBC-EPA (p < 0.0001) were higher than in CG, while DHA levels did not differ between IG-R and CG. Regular fish consumption during complementary feeding enhances infant EPA and DHA status. The usage of rapeseed oil in small amounts concordant with EU-law for commercial meals enhances endogenic EPA-synthesis, but does not affect DHA status. Provision of oily fish with complementary feeds is advisable to prevent a decline of DHA status. www.clinicaltrials.gov , identifier: NCT01487889, title: Polyunsaturated fatty acids in child nutrition-a German multimodal optimisation study (PINGU).

Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.

PubMed Central

Cohen, R D; Castellani, L W; Qiao, J H; Van Lenten, B J; Lusis, A J; Reue, K

1997-01-01

Transgenic mouse lines carrying several copies of the mouse apo A-IV gene were produced. Lipoprotein composition and function, and aortic lesion development were examined. Apo A-IV levels in the plasma of transgenic mice were elevated threefold compared with nontransgenic littermates on a chow diet, and sixfold in mice fed an atherogenic diet. Plasma concentrations of total cholesterol, HDL cholesterol, triglycerides, and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0.05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and free fatty acids (P < 0.05), and lower levels of unesterified cholesterol (P < 0.05), than nontransgenic littermates. Expression of the apo A-IV transgene had a protective effect against the formation of diet-induced aortic lesions, with transgenics exhibiting lesion scores of approximately 30% those seen in control mice. HDL-sized lipoproteins isolated from transgenic mice fed the atherogenic diet promoted cholesterol efflux from cholesterol-loaded human monocytes more efficiently than comparable lipoproteins from nontransgenic counterparts. Plasma from transgenics also exhibited higher endogenous cholesterol esterification rates. Taken together, these results suggest that apo A-IV levels influence the metabolism and antiatherogenic properties of HDL. PMID:9109435

[Quantitative determination of the main metabolites of acetylsalicylic acid/2nd communication: the concentrations of salicylic acid and its metabolites in patients with renal insufficiency (author's transl)].

PubMed

Daneels, R; Loew, D; Pütter, J

1975-07-01

Quantitative Determination of the Main Metabolites of Acetylsalicylic Acid / 2nd Communication: The concentrations of salicylic acid and its metabolies in patients with renal insufficiency 9 patients suffering from renal insufficiencies of varing degrees and treated regularly by hemodialysis were given 1.5 g Colfarit (microcapsulated acetyl salicylic acid) as a single dose. The concentrations of salicylic acid (SA), salicyluric acid (SU), further salicylic acid conjugates (SAC) and salicyluric acid conjugates (SUC) were determined in the blood plasma. Likewise urea and creatinine were determined. SA concentration decreased continually and, at the end of the trial (72 h after application), had vanished almost completely from the plasma of most patients. SU increased at first and decreased afterwards. With the exception of the dailysis time SAC and SUC increased during the trial. After 3 days the SUC level was more than 50% of total salicylate (SSS) in most patients. SSS (the sum of SA + SU + SAC + SUC) did not change very much before dialysis, but showed a rather high decrease during the first hours of dialysis. tafter dialysis the SSS levels rose again, apparently as a consequence of a redistribution and of the synthesis of conjugates with decreased tissue affinity. It could be shown that SSS in the blood plasma does not parallel SSS in the whole body. The interindividual variation of SA metabolism as well as the variation of the biological blank values was rather high. The results are discussed with regard to salicylate pharmacokinetics in renal insufficiency and to normal salicylate metabolism.

Renal norepinephrine spillover during infusion of nonesterified fatty acids.

PubMed

Grekin, Roger J; Ngarmukos, Chardpra-Orn; Williams, David M; Supiano, Mark A

2005-03-01

Sympathetic activity and renal norepinephrine spillover are increased in obese individuals. We have reported that infusion of nonesterified fatty acids increases blood pressure in animals through stimulation of the sympathetic nervous system. In this study, we assessed the effect of increasing circulating nonesterified fatty acids on systemic and renal norepinephrine kinetics in healthy adults by infusing fat emulsion and heparin for 4 h. (3)H-norepinephrine was infused for 60 min before and again during the last hour of the fatty acid infusion to assess norepinephrine kinetics. Renal venous blood samples were obtained to calculate renal norepinephrine spillover. Nonesterified fatty acid levels increased threefold during the first hour and remained elevated throughout the study. Arterial and renal venous plasma norepinephrine levels fell by 15% and 20%, respectively, during the infusion (P < .05 for both). Kinetic analysis indicated that systemic release of norepinephrine into an extravascular compartment decreased from 11.6 +/- 1.1 to 10.0 +/- 1.3 nmol/min/m(2) (P = .067) and renal venous norepinephrine spillover decreased from 454 +/- 54 pmol/min (P = .055). These results indicate that nonesterified fatty acids do not have a direct stimulating effect on whole-body or renal sympathetic activity. It is possible that increased plasma levels of fatty acids serve as a signal to decrease sympathetic tone during the fasting state.

The Effects of Graded Levels of Calorie Restriction: XIII. Global Metabolomics Screen Reveals Graded Changes in Circulating Amino Acids, Vitamins, and Bile Acids in the Plasma of C57BL/6 Mice.

PubMed

Green, Cara L; Soltow, Quinlyn A; Mitchell, Sharon E; Derous, Davina; Wang, Yingchun; Chen, Luonan; Han, Jing-Dong J; Promislow, Daniel E L; Lusseau, David; Douglas, Alex; Jones, Dean P; Speakman, John R

2018-04-30

Calorie restriction (CR) remains the most robust intervention to extend life span and improve health span. Using a global mass spectrometry-based metabolomics approach, we identified metabolites that were significantly differentially expressed in the plasma of C57BL/6 mice, fed graded levels of calorie restriction (10% CR, 20% CR, 30% CR, and 40% CR) compared with mice fed ad libitum for 12 hours a day. The differential expression of metabolites increased with the severity of CR. Pathway analysis revealed that graded CR had an impact on vitamin E and vitamin B levels, branched chain amino acids, aromatic amino acids, and fatty acid pathways. The majority of amino acids correlated positively with fat-free mass and visceral fat mass, indicating a strong relationship with body composition and vitamin E metabolites correlated with stomach and colon size, which may allude to the beneficial effects of investing in gastrointestinal organs with CR. In addition, metabolites that showed a graded effect, such as the sphinganines, carnitines, and bile acids, match our previous study on liver, which suggests not only that CR remodels the metabolome in a way that promotes energy efficiency, but also that some changes are conserved across tissues.

Effects of cadmium ingestion and food restriction on energy metabolism and tissue metal concentrations in mallard ducks

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

Di Giulio, R.T.; Scanlon, P.F.

1985-08-01

The single and combined effects of cadmium ingestion and food restriction were examined in a 42-day experiment with male, juvenile mallard ducks. A 2 x 3 factorial design was employed consisting of two levels of food supply (ad libitum and 55% of ad libitum intake) and three levels of cadmium in the food (0, 5 or 50 ..mu..g Cd/g food). Cadmium ingestion alone had no effect on body or tissue weights, liver glycogen, plasma concentrations of glucose, urea, uric acid, nonesterified fatty acids (NEFA), triiodothyronine (T/sub 3/), thyroxine (T/sub 4/), or plasma or adrenal concentrations of corticosterone. The food restrictionmore » resulted in reduced body weights and reduced weights of livers, kidneys, and testes, increased adrenal weights, reduced liver glycogen, increased plasma NEFA concentrations, reduced plasma T/sub 3/ and T/sub 4/ concentrations, and increased adrenal corticosterone concentrations. In combination with the food restrictions, cadmium ingestion further reduced plasma T/sub 3/ concentrations and a similar trend was noted for T/sub 4/. Additionally, the highest plasma NEFA concentrations and highest plasma and adrenal concentrations of corticosterone were observed in food-restricted ducks receiving the highest level of dietary cadmium. These results suggest that ability of cadmium ingestion to enhanced food restriction-induced alterations in energy metabolism at levels of dietary cadmium that are by themselves without apparent effect. Also, cadmium ingestion resulted in increased kidney concentrations of copper and zinc: this effect on kidney zinc concentrations was increased in food-restricted ducks.« less

Enhanced erythrocytic lipid peroxides and reduced plasma ascorbic acid, and alteration in blood trace elements level in dairy cows with mastitis.

PubMed

Ranjan, R; Swarup, D; Naresh, R; Patra, R C

2005-01-01

Oxidative stress has been associated in several inflammatory conditions and incriminated in the pathogenesis of many diseases. However, little information is available on the status of plasma antioxidant levels, essential components of important antioxidant enzymes such as copper, zinc and selenium in blood, and the end product of oxidative damage to the erythrocytic polyunsaturated fatty acids in inflammatory udder conditions. Blood samples were collected from three groups of dairy cows, with 21 in each group: animals with healthy udder, clinical mastitis, and subclinical mastitis. These animals were randomly selected from a herd on the basis of the California mastitis test, somatic cell count and total bacterial count. The mean plasma ascorbic acid concentration was significantly lower in cows with subclinical (p = 0.004) and clinical mastitis (p = 0.000) and the erythrocytic lipid peroxide levels were significantly (p = 0.000) higher in clinical mastitis as compared to controls. There was a significant decrease in mean blood zinc concentration in subclinical (p = 0.005) and clinical mastitis (p = 0.000), but an increase in mean blood copper level in the clinical mastitis group. It was concluded that the blood antioxidant status declines in inflammatory udder conditions, suggesting that incorporation of antioxidants may help in better management of mastitis in dairy cows.

Does taurine deficiency cause metabolic bone disease and rickets in polar bear cubs raised in captivity?

PubMed

Chesney, Russell W; Hedberg, Gail E; Rogers, Quinton R; Dierenfeld, Ellen S; Hollis, Bruce E; Derocher, Andrew; Andersen, Magnus

2009-01-01

Rickets and fractures have been reported in captive polar bears. Taurine (TAU) is key for the conjugation of ursodeoxycholic acid (UDCA), a bile acid unique to bears. Since TAU-conjugated UDCA optimizes fat and fat-soluble vitamin absorption, we asked if TAU deficiency could cause vitamin D malabsorption and lead to metabolic bone disease in captive polar bears. We measured TAU levels in plasma (P) and whole blood (WB) from captive and free-ranging cubs and adults, and vitamin D3 and TAU concentrations in milk samples from lactating sows. Plasma and WB TAU levels were significantly higher in cubs vs captive and free-ranging adult bears. Vitamin D in polar bear milk was 649.2 +/- 569.2 IU/L, similar to that found in formula. The amount of TAU in polar bear milk is 3166.4 +/- 771 nmol/ml, 26-fold higher than in formula. Levels of vitamin D in bear milk and formula as well as in plasma do not indicate classical nutritional vitamin D deficiency. Higher dietary intake of TAU by free-ranging cubs may influence bile acid conjugation and improve vitamin D absorption.

Dose-dependent consumption of farmed Atlantic salmon (Salmo salar) increases plasma phospholipid n-3 fatty acids differentially

PubMed Central

Raatz, Susan K.; Rosenberger, Thad A.; Johnson, LuAnn K.; Wolters, William W.; Burr, Gary S; Picklo, Matthew J.

2013-01-01

Enhanced omega-3 fatty acid (n-3) intake benefits cardiovascular disease (CVD) risk reduction. Increasing consumption at a population level may be better addressed by diet than through supplementation. However, limited data are available on the effect of the dose response to fish intake on plasma levels of n-3 fatty acids. To compare the effects of different doses of farmed Atlantic salmon on plasma phospholipid fatty acid (PLFA) proportions and CVD risk biomarkers (glucose, insulin, HOMAIR, hsCRP, and IL-6) in healthy subjects we performed a randomized 3-period cross-over designed trial (4 wk treatment, 4-8 wk washout) to compare the effects of twice/wk consumption of farmed Atlantic salmon at doses of 90, 180, and 270 g in 19 apparently healthy men and women with a mean age of aged 40-65 years and a BMI between 25-34.9 kg/m2. All study visits were conducted at the USDA, ARS Grand Forks Human Nutrition Research Center. EPA and total n-3 were increased (p<0.05) by all treatments in a dose response manner, with total n-3 of 8.03 ± 0.26 and 9.21 ± 0.26 % for 180 and 270 g doses, respectively. Linoleic acid did not change in response to treatment while arachidonic acid (P<0.05) and total omega-6 fatty acids (n-6) decreased dose dependently (<0.0001). The addition of farmed Atlantic salmon to the diet twice/wk for 4 wk at portions of 180g and 270g modifies PLFA proportions of n-3 and n-6 in a level associated with decreased risk for CVD. PMID:23351633

A Randomized Controlled Trial of the Effects of Febuxostat Therapy on Adipokines and Markers of Kidney Fibrosis in Asymptomatic Hyperuricemic Patients With Diabetic Nephropathy

PubMed Central

Beddhu, Srinivasan; Filipowicz, Rebecca; Wang, Bin; Wei, Guo; Chen, Xiaorui; Roy, Abinash C.; DuVall, Scott L.; Farrukh, Hanadi; Habib, Arsalan N.; Bjordahl, Terrence; Simmons, Debra L.; Munger, Mark; Stoddard, Greg; Kohan, Donald E.; Greene, Tom; Huang, Yufeng

2016-01-01

Background: In observational studies, higher uric acid levels are associated with metabolic syndrome, diabetes, and kidney disease. Objective: The objective of this study is to examine whether reduction of plasma uric acid with febuxostat, a xanthine oxido reductase inhibitor, impacts adipose tissue oxidative stress, adipokines, and markers of systemic inflammation or kidney fibrosis. Design: This was a double-blinded randomized controlled trial. Setting: Academic university setting was used. Patients: Overweight or obese adults with hyperuricemia and type 2 diabetic nephropathy were included. Measurements: Adipose tissue thiobarbituric acid reducing substances (TBARS) and adiponectin concentrations and urinary transforming growth factor–β (TGF-β) were primary endpoints. Plasma C-reactive protein, high molecular weight–adiponectin, interleukin–6, tumor necrosis factor–α, and TBARS and albuminuria were among predefined secondary endpoints. Methods: Participants were randomly assigned to febuxostat (n = 40) or matching placebo (n = 40) and followed for 24 weeks. Results: Baseline plasma uric acid levels were 426 ± 83 µmol/L; 95% completed the study. Estimated glomerular filtration rate (eGFR) declined from 54 ± 17 mL/min/1.73 m2 at baseline to 51 ± 17 mL/min/1.73 m2 at 24 weeks (P = .05). In separate mixed-effects models, compared with placebo, febuxostat reduced uric acid by 50% (P < .001) but had no significant effects on subcutaneous adipose tissue TBARS (−7.4%, 95% confidence interval [CI], 57.4%-101.4%) or adiponectin (6.7%, 95% CI, 26.0%-53.8%) levels or urinary TGF-β/creatinine ratio (18.0%, 95% CI, 10.0%-54.8%) or secondary endpoints. Limitations: Relatively modest sample size and short duration of follow-up. Conclusions: In this population with progressive diabetic nephropathy, febuxostat effectively reduced plasma uric acid. However, no detectable effects were observed for the prespecified primary or secondary endpoints. Trial Registration: The study was registered in clinicaltrials.gov (NCT01350388). PMID:28270924

[Plasma level and metabolism of vitamin A (Vitadral) in women of reproductive age].

PubMed

Peiker, G; Eckhoff, C; Nau, H

1991-01-01

Using a sensitive HPLC method, plasma concentrations of vitamin A and metabolites were measured from 6 female volunteers who had taken once daily 0.46 mg/kg BW retinol palmitate (Vitadral) for 10 days. The metabolites all-trans- and 13-cis-retinoic acid were increased significantly (2- and 5-fold, resp.) 6 h after the ist intake. 13-cis-4-oxo retinoic acid the 10th intake in the morning of the 10th day (9.22 +/- 2.77 ng/ml, 4-fold increase). The results show continuous increase of retinoic acids, which have to be considered as potential teratogens, after administration of vitamin A. The plasma concentration of retinol itself did not change, whereas only short-term increases were observed for retinol esters.

Exchanging partially hydrogenated fat for palmitic acid in the diet increases LDL-cholesterol and endogenous cholesterol synthesis in normocholesterolemic women.

PubMed

Sundram, Kalyana; French, Margaret A; Clandinin, M Thomas

2003-08-01

Partial hydrogenation of oil results in fats containing unusual isomeric fatty acids characterized by cis and trans configurations. Hydrogenated fats containing trans fatty acids increase plasma total cholesterol (TC) and LDL-cholesterol while depressing HDL-cholesterol levels. Identifying the content of trans fatty acids by food labeling is overshadowed by a reluctance of health authorities to label saturates and trans fatty acids separately. Thus, it is pertinent to compare the effects of trans to saturated fatty acids using stable isotope methodology to establish if the mechanism of increase in TC and LDL-cholesterol is due to the increase in the rate of endogenous synthesis of cholesterol. Ten healthy normocholesterolemic female subjects consumed each of two diets containing approximately 30% of energy as fat for a fourweek period. One diet was high in palmitic acid (10.6% of energy) from palm olein and the other diet exchanged 5.6% of energy as partially hydrogenated fat for palmitic acid. This fat blend resulted in monounsaturated fatty acids decreasing by 4.9 % and polyunsaturated fats increasing by 2.7%. The hydrogenated fat diet treatment provided 3.1% of energy as elaidic acid. For each dietary treatment, the fractional synthesis rates for cholesterol were measured using deuterium-labeling procedures and blood samples were obtained for blood lipid and lipoprotein measurements. Subjects exhibited a higher total cholesterol and LDL-cholesterol level when consuming the diet containing trans fatty acids while also depressing the HDL-cholesterol level. Consuming the partially hydrogenated fat diet treatment increased the fractional synthesis rate of free cholesterol. Consumption of hydrogenated fats containing trans fatty acids in comparison to a mixtur e of palmitic and oleic acids increase plasma cholesterol levels apparently by increasing endogenous synthesis of cholesterol.

Biological activity of alligator, avian, and mammalian insulin in juvenile alligators: plasma glucose and amino acids.

PubMed

Lance, V A; Elsey, R M; Coulson, R A

1993-02-01

The biological activity of alligator, turkey, and bovine insulin on plasma glucose and plasma amino acids was tested in fasted juvenile alligators. Preliminary experiments showed that the stress associated with taking the initial blood sample resulted in a hyperglycemic response lasting more than 24 hr. Despite repeated bleedings no additional hyperglycemic events occurred, and blood glucose declined slowly over the next 7 days. Under these conditions the smallest dose of insulin eliciting a hypoglycemic response was 40 micrograms/kg body wt. A dose of 400 micrograms/kg body wt of either alligator or bovine insulin caused a pronounced hypoglycemia by 12 hr postinjection. Maximum decline in plasma glucose occurred at 24 to 36 hr with a slow return to control levels by 120 hr. There were no significant differences in the hypoglycemic responses to any of the three insulins tested. The decline in plasma amino acids was much more rapid than the decline in plasma glucose in response to insulin. Even at the 40 micrograms/kg body wt dose a significant difference from saline-injected control was seen at 2 hr postinjection. Maximum decline in plasma amino acids occurred at 8 to 12 hr with a return to baseline by 36 hr. These results show that the relatively conservative changes in the sequence of alligator insulin (three amino acid substitutions in the B-chain compared with that of chicken) have little effect on biological activity and that alligator insulin receptors do not appear to discriminate among the three insulins.

Influence of the collection tube on metabolomic changes in serum and plasma.

PubMed

López-Bascón, M A; Priego-Capote, F; Peralbo-Molina, A; Calderón-Santiago, M; Luque de Castro, M D

2016-04-01

Major threats in metabolomics clinical research are biases in sampling and preparation of biological samples. Bias in sample collection is a frequently forgotten aspect responsible for uncontrolled errors in metabolomics analysis. There is a great diversity of blood collection tubes for sampling serum or plasma, which are widely used in metabolomics analysis. Most of the existing studies dealing with the influence of blood collection on metabolomics analysis have been restricted to comparison between plasma and serum. However, polymeric gel tubes, which are frequently proposed to accelerate the separation of serum and plasma, have not been studied. In the present research, samples of serum or plasma collected in polymeric gel tubes were compared with those taken in conventional tubes from a metabolomics perspective using an untargeted GC-TOF/MS approach. The main differences between serum and plasma collected in conventional tubes affected to critical pathways such as the citric acid cycle, metabolism of amino acids, fructose and mannose metabolism and that of glycerolipids, and pentose and glucuronate interconversion. On the other hand, the polymeric gel only promoted differences at the metabolite level in serum since no critical differences were observed between plasma collected with EDTA tubes and polymeric gel tubes. Thus, the main changes were attributable to serum collected in gel and affected to the metabolism of amino acids such as alanine, proline and threonine, the glycerolipids metabolism, and two primary metabolites such as aconitic acid and lactic acid. Therefore, these metabolite changes should be taken into account in planning an experimental protocol for metabolomics analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Plasma growth hormone (GH), insulin and amino acid responses to arginine with or without aspartic acid in pigs. Effect of the dose.

PubMed

Cochard, A; Guilhermet, R; Bonneau, M

1998-01-01

The aim of the present study was to examine, for the first time in pigs, the dose-dependent effect of arginine (ARG) on growth hormone (GH) and insulin release and the effect of the combined ARG and aspartic acid (ASP) treatment on GH and insulin release. ARG (0.5 or 1 g/kg body weight) with or without an equimolar supplement of ASP (0.38 or 0.76 g/kg, respectively) was administered in piglets via the duodenum. ARG increased plasma arginine, ornithine, urea, proline and branched chain amino acid concentrations. ASP increased specifically plasma aspartic acid, glutamic acid, alanine and citrulline concentrations. Plasma insulin increased with no apparent difference between treatments. Maximum GH level and the area under the GH curve (AUC) were increased in a dose-dependent manner in response to ARG treatment. GH response to the combined ARG and ASP treatment (ARGASP) was delayed compared to ARG alone and was not dose-dependent. AUC for GH after ARGASP treatments were intermediate between those observed after the two ARG doses. Our data suggest that high ASP doses transiently inhibit and delay ARG-induced GH release in pigs and that an equimolar supplement of ASP stimulates or inhibits ARG-induced GH release depending on the dose used.

Laying hen responses to acute heat stress and carbon dioxide supplementation: I. Blood gas changes and plasma lactate accumulation.

PubMed

Koelkebeck, K W; Odom, T W

1994-04-01

Exposure to heat stress lowered partial pressure of arterial blood carbon dioxide (paCO2), arterial blood bicarbonate ion (HCO3-), but increased arterial blood pH (pHa) and plasma lactate (LA). Increasing ambient carbon dioxide (CO2) to 1.5% increased paCO2 from hypocapnic levels to normocapnic levels, raised HCO3-, lowered pHa and plasma LA to pre-heat stress levels. Following CO2 treatment, respiratory alkalosis conditions returned. It was evident in this study that increasing ambient chamber CO2 to 1.5% was effective in ameliorating acid-base disturbances and reducing elevated levels of plasma LA which normally develops when laying hens are subjected to an acute heat stress exposure.

Reference values of amino acids and of common clinical chemistry in plasma of healthy infants aged 1 and 4 months.

PubMed

Haschke-Becher, Elisabeth; Kainz, Alexander; Bachmann, Claude

2016-01-01

To compare plasma levels of amino acids and clinical chemistry parameters in healthy infants at 1 and 4 months of age and to establish corresponding reference limits. Data of three multicenter studies assessing the safety of new infant formulas were used. During these studies infants of both age-groups were either breast-fed or received formulas of low or high protein content. All samples were analyzed centrally in the same accredited laboratory. Plasma was collected from 521 infants in total, 157 boys and 135 girls aged 1 month and 121 boys and 108 girls aged 4 months. At the age of 1 month, 62 infants had received exclusively breast milk, 198 exclusively formula, and 27 both; in the 4-months age group corresponding numbers were 49, 158 and 18, respectively; for 9 infants, diet was unknown. Concentrations of most amino acids and clinical chemistry parameters differed significantly between both ages. Regardless of age, most plasma amino acid levels were comparable or lower in breast-fed than in formula-fed infants whereas at 1 month of age most clinical chemistry parameters were higher. While in breast-fed infants the plasma urea concentration decreased over 4 months of age, it increased in formula-fed infants. There were significant differences between infants fed a low and high protein formula. At both ages, high protein formulas resulted in significantly higher threonine, 2-aminobutyrate, and urea concentrations. For clinical use, age- and diet specific reference limits in infants are warranted.

Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice.

PubMed

Meissner, Maxi; Lombardo, Elisa; Havinga, Rick; Tietge, Uwe J F; Kuipers, Folkert; Groen, Albert K

2011-10-01

Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in hypercholesterolemic mice. Male LDLR-deficient mice (8 weeks old) had either access to a voluntary running wheel for 12 weeks (RUN) or remained sedentary (CONTROL). Both groups were fed a western-type/high cholesterol diet. Running activity and food intake were recorded. At 12 weeks of intervention, feces, bile and plasma were collected to determine fecal, biliary and plasma parameters of cholesterol metabolism and plasma cytokines. Atherosclerotic lesion size was determined in the aortic root. RUN weighed less (∼13%) while food consumption was increased by 17% (p=0.004). Plasma cholesterol levels were decreased by 12% (p=0.035) and plasma levels of pro-atherogenic lipoproteins decreased in RUN compared to control. Running modulated cholesterol catabolism by enhancing cholesterol turnover: RUN displayed an increased biliary bile acid secretion (68%, p=0.007) and increased fecal bile acid (93%, p=0.009) and neutral sterol (33%, p=0.002) outputs compared to control indicating that reverse cholesterol transport was increased in RUN. Importantly, aortic lesion size was decreased by ∼33% in RUN (p=0.033). Voluntary wheel running reduces atherosclerotic burden in hypercholesterolemic mice. An increased cholesterol turnover, specifically its conversion into bile acids, may underlie the beneficial effect of voluntary exercise in mice. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Biochemistry of blood plasma and some parameters of antioxidant status in rats with polyhypovitaminosis of varying severity.

PubMed

Kodentsova, V M; Vrzhesinskaya, O A; Beketova, N A; Soto, S Kh; Karagodina, Z V; Sharanova, N E; Baturina, V A

2013-02-01

In rats with profound vitamin deficiency, blood plasma level of triglycerides significantly decreased by 1.6 times, potassium ions by 5%, uric acid by 23%, ALT and AST by 1.4 times, while the levels of glucose increased by 32%, iron by 31%, urea by 58%, and alkaline phosphatase by 19%. Plasma level of phosphorus tended to decrease and ionized calcium concentration tended to increase. Severe deficiency of all vitamins is accompanied by pronounced accumulation of MDA in the plasma and liver together with simultaneous increase in the level of coenzyme Q10 by 4.6 times and decrease in vitamin C content by 21.4% in the rat liver compared to the control. It was found that severe combined deficiency of vitamins for 4 weeks produced considerable multidirectional alterations in diagnostically important metabolic parameters in rat plasma.

[Endogenous nociceptin level in ischemic stroke: connection to serotonin system].

PubMed

Tekes, Kornélia; Hantos, Mónika; Bátor, György; Gyenge, Melinda; Laufer, Rudolf; Folyovich, András

2006-06-01

Particular role of the heptadecapeptide nociceptin (orphanin FQ), the endogenous agonist of the NOP receptor, has been widely demonstrated in the regulation of pain sensation and anxiety-related behavior. In our best knowledge this is the first study reporting plasma nociceptin levels in 26 acute stroke and 6 transiens ischemic attack (TIA) patients. We have found significantly elevated plasma nociceptin levels in all the three groups of patients studied (stroke influencing the carotis or the lacunar region and TIA). We suggest that elevated plasma nociceptin level is the consequence of stroke as in the group of patients recovered from previous stroke was found similar the control value. Plasma serotonin level was found non-significantly decreased in patients with stroke influencing the lacunar region and TIA patients. However the plasma 5-hydroxy-indoleacetic acid (5HIAA) levels were found significantly elevated in patient groups with stroke influencing both the carotis and the lacunar regions. Data may serve as further evidence for the serotonergic dysregulation in stroke.

Improvement of the omega 3 index of healthy subjects does not alter the effects of dietary saturated fats or n-6PUFA on LDL profiles.

PubMed

Dias, Cintia B; Amigó, Núria; Wood, Lisa G; Mallol, Roger; Correig, Xavier; Garg, Manohar L

2017-03-01

Dietary fat composition is known to modulate circulating lipid and lipoprotein levels. Although supplementation with long chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) has been shown to reduce plasma triglyceride levels, the effect of the interactions between LCn-3PUFA and the major dietary fats consumed has not been previously investigated. In a randomized controlled parallel design clinical intervention, we examined the effect of diets rich in either saturated fatty acids (SFA) or omega-6 polyunsaturated fatty acids (n-6PUFA) on plasma lipid levels and lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) in subjects with an adequate omega 3 index. Twenty six healthy subjects went through a four-week pre-supplementation period with LCn-3PUFA and were then randomized to diets rich in either n-6PUFA or SFA both supplemented with LCn-3PUFA. The diet rich in n-6PUFA decreased low density lipoprotein (LDL) particle concentration (-8%, p=0.013) and LDL cholesterol (LDL-C) level (-8%, p=0.021), while the saturated fat rich diet did not affect LDL particle concentration or LDL-C levels significantly. Nevertheless, dietary saturated fatty acids increased LCn-3PUFA in plasma and tissue lipids compared with n-6PUFA, potentially reducing other cardiovascular risk factors such as inflammation and clotting tendency. Improvement on the omega 3 index of healthy subjects did not alter the known effects of dietary saturated fats and n-6PUFA on LDL profiles. Copyright © 2016 Elsevier Inc. All rights reserved.

Assay of calcium borogluconate veterinary medicines for calcium gluconate, boric acid, phosphorus, and magnesium by using inductively coupled plasma emission spectrometry

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

Lyons, D.J.; Spann, K.P.

1985-03-01

An inductively coupled plasma spectrometric method is described for the determination of 4 elements (Ca, B, P, and Mg) in calcium borogluconate veterinary medicines. Samples are diluted, acidified, and sprayed directly into the plasma. Reproducibility relative confidence intervals for a single sample assay are +/- 1.4% (calcium), +/- 1.8% (boron), +/- 2.6% (phosphorus), and +/- 1.4% (magnesium). The total element concentrations for each of 4 elements compared favorably with concentrations determined by alternative methods. Formulation estimates of levels of calcium gluconate, boric acid, phosphorus, and magnesium salts can be made from the analytical data.

Discovery and fine-mapping of loci associated with monounsaturated fatty acids through trans-ethnic meta-analysis in Chinese and European populations

USDA-ARS?s Scientific Manuscript database

Monounsaturated fatty acids (MUFAs) are unsaturated fatty acids with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels were associated with cardiometabolic disorders including cardiovascular disea...

Influence of stearic acid on hemostatic risk factors in humans.

PubMed

Tholstrup, Tine

2005-12-01

Stearic acid has been claimed to be prothrombotic. Elevated plasma factor VII coagulant activity (FVIIc) may raise the risk of coronary thrombosis in the event of plaque rupture. Fibrinogen, an acute-phase protein, is necessary for normal blood clotting; however, elevated levels of fibrinogen increase the risk of coronary heart disease (CHD). Here I report the results of three controlled, human dietary intervention studies, which used a randomized crossover design to investigate the hemostatic effects of stearic acid-rich test diets in healthy young men. A diet high in stearic acid (shea butter) resulted in a 13% lower fasting plasma FVIIc than a high palmitic acid diet, and was 18% lower than a diet high in myristic and lauric acids (P = 0.001) after 3 wk of intervention. The stearic acid-rich test fat increased plasma fibrinogen concentrations slightly compared with the myristic-lauric acid diet (P < 0.01). When investigating the acute effects of fatty meals, those high in stearic acid (synthesized test fat) resulted in a smaller postprandial increase in FVII than those high in trans and oleic FA, indicating a smaller increase in activated FVII after ingesting stearic acid compared with fats high in monounsaturated FA, probably caused by lower postprandial lipemia. Thus, the present investigations did not find dietary stearic acid to be more thrombogenic, in either fasting effects compared with other long-chain FA, or in acute effects compared with dietary unsaturated FA, including trans monounsaturated FA. The slightly increased effect on fasting plasma fibrinogen may be biologically insignificant, but it should be investigated further.

Clozapine response and plasma catecholamines and their metabolites.

PubMed

Green, A I; Alam, M Y; Sobieraj, J T; Pappalardo, K M; Waternaux, C; Salzman, C; Schatzberg, A F; Schildkraut, J J

1993-02-01

The atypical neuroleptic clozapine has an unusual profile of clinical effects and a distinctive spectrum of pharmacological actions. Plasma measures of catecholamines and their metabolites have been used in the past to study the action of typical neuroleptics. We obtained longitudinal assessments of plasma measures of dopamine (pDA), norepinephrine (pNE), and their metabolites, homovanillic acid (pHVA) and 3-methoxy-4-hydroxyphenylglycol (pMHPG), in eight treatment-resistant or treatment-intolerant schizophrenic patients who were treated with clozapine for 12 weeks following a prolonged drug-washout period. Our findings from the study of these eight patients suggest the following: Plasma levels of HVA and possibly NE derived from the neuroleptic-free baseline period may predict response to clozapine; plasma levels of HVA and MHPG decrease during the initial weeks of treatment in responders but not in nonresponders; and plasma levels of DA and NE increase in both responders and nonresponders to clozapine.

A case of hereditary angioneurotic oedema, successfully treated with ε-aminocaproic acid. Studies on C'1 esterase inhibitor, C'1 activation, plasminogen level and histamine metabolism

PubMed Central

Lundh, B.; Laurell, Anna-Brita; Wetterqvist, H.; White, T.; Granerus, G.

1968-01-01

A patient with clinical and laboratory findings characteristic of hereditary angioneurotic oedema was investigated. The patient was observed for a period of 5 weeks, during which he had four attacks. ε-Aminocaproic acid (EACA) was then given continuously for 5 months, during which time the patient had no attacks. Attacks reappeared on withdrawal of EACA. Trans-4-(aminomethyl) cyclohexane carboxylic acid (AMCA®) was found to be equally effective in later therapeutic trials. C'1 esterase inhibitor was found in low concentration in defibrinated plasma also during attacks. ε-Aminocaproic acid (EACA) produced no significant change of the inhibitor content. C'1 esterase inhibitor disappeared on incubation of defibrinated plasma from the patient at 37°C for 40 min, and C'1 esterase was generated. The generation time of C'1 esterase increased with increasing the concentration of EDTA in the test solution. The C'1 esterase inhibitor content of defibrinated plasma from the patient, varied with the C'1 esterase generation time, the coefficient of correlation being higher in plasma sampled before treatment with EACA. Plasminogen and α2-macroglobulin were within the normal ranges, also during attacks. EACA markedly depressed the plasminogen level, which rapidly returned to normal on withdrawal of the drug. The studies on histamine metabolism revealed no significant changes with the exception of the urinary excretion of histamine, which was moderately increased towards the end of the period studied. On the days the patient received EACA the urine never contained 1-methylimidazole-5-acetic acid which was present in all the other specimens of urine examined. The basal gastric acid secretion was increased. PMID:5701955

Hypothalamic control of pituitary and adrenal hormones during hypothermia.

PubMed

Okuda, C; Miyazaki, M; Kuriyama, K

1986-01-01

In order to investigate neuroendocrinological mechanisms of hypothermia, we determined the changes in plasma concentrations of corticosterone (CS), prolactin (PRL), and thyrotropin (TSH), and their correlations with alterations in hypothalamic dopamine (DA) and thyrotropin releasing hormone (TRH), in rats restrained and immersed in a water bath at various temperatures. A graded decrease of body temperature induced a progressive increase in the plasma level of CS, whereas that of PRL showed a drastic decrease. The plasma level of TSH also showed an increase during mild hypothermia (about 35 degrees C), but this increase was not evident during profound hypothermia (below 24 degrees C). The changes in these hormones were readily reversed by rewarming animals. Although DA content in the hypothalamus was not affected, its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), showed an increase following the decrease of body temperature. Pretreatment of the animals with sulpiride, a D2-antagonist, prevented the hypothermia-induced inhibition of PRL release. Hypothalamic TRH was significantly decreased during mild hypothermia, and it returned to control levels after rewarming. These results suggest that the decrease in plasma PRL induced by hypothermia may be associated with the activation of hypothalamic DA neurons, whereas the increase in plasma TSH during mild hypothermia seems to be caused by the increased release of TRH in the hypothalamus.

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters[S

PubMed Central

Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen

2017-01-01

The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI. PMID:27940481

Regulation of lipid metabolism by obeticholic acid in hyperlipidemic hamsters.

PubMed

Dong, Bin; Young, Mark; Liu, Xueqing; Singh, Amar Bahadur; Liu, Jingwen

2017-02-01

The farnesoid X receptor (FXR) plays critical roles in plasma cholesterol metabolism, in particular HDL-cholesterol (HDL-C) homeostasis. Obeticholic acid (OCA) is a FXR agonist being developed for treating various chronic liver diseases. Previous studies reported inconsistent effects of OCA on regulating plasma cholesterol levels in different animal models and in different patient populations. The mechanisms underlying its divergent effects have not yet been thoroughly investigated. The scavenger receptor class B type I (SR-BI) is a FXR-modulated gene and the major receptor for HDL-C. We investigated the effects of OCA on hepatic SR-BI expression and correlated such effects with plasma HDL-C levels and hepatic cholesterol efflux in hyperlipidemic hamsters. We demonstrated that OCA induced a time-dependent reduction in serum HDL-C levels after 14 days of treatment, which was accompanied by a significant reduction of liver cholesterol content and increases in fecal cholesterol in OCA-treated hamsters. Importantly, hepatic SR-BI mRNA and protein levels in hamsters were increased to 1.9- and 1.8-fold of control by OCA treatment. Further investigations in normolipidemic hamsters did not reveal OCA-induced changes in serum HDL-C levels or hepatic SR-BI expression. We conclude that OCA reduces plasma HDL-C levels and promotes transhepatic cholesterol efflux in hyperlipidemic hamsters via a mechanism involving upregulation of hepatic SR-BI.

Molecular Properties of Guar Gum and Pectin Modify Cecal Bile Acids, Microbiota, and Plasma Lipopolysaccharide-Binding Protein in Rats

PubMed Central

Ghaffarzadegan, Tannaz; Marungruang, Nittaya; Fåk, Frida; Nyman, Margareta

2016-01-01

Bile acids (BAs) act as signaling molecules in various physiological processes, and are related to colonic microbiota composition as well as to different types of dietary fat and fiber. This study investigated whether guar gum and pectin—two fibers with distinct functional characteristics—affect BA profiles, microbiota composition, and gut metabolites in rats. Low- (LM) or high-methoxylated (HM) pectin, and low-, medium-, or high-molecular-weight (MW) guar gum were administered to rats that were fed either low- or high-fat diets. Cecal BAs, short-chain fatty acids (SCFA) and microbiota composition, and plasma lipopolysaccharide-binding protein (LBP) levels were analyzed, by using novel methodologies based on gas chromatography (BAs and SCFAs) and 16S rRNA gene sequencing on the Illumina MiSeq platform. Strong correlations were observed between cecal BA and SCFA levels, microbiota composition, and portal plasma LBP levels in rats on a high-fat diet. Notably, guar gum consumption with medium-MW increased the cecal amounts of cholic-, chenodeoxycholic-, and ursodeoxycholic acids as well as α-, β-, and ω-muricholic acids to a greater extent than other types of guar gum or the fiber-free control diet. In contrast, the amounts of cecal deoxycholic- and hyodeoxycholic acid were reduced with all types of guar gum independent of chain length. Differences in BA composition between pectin groups were less obvious, but cecal levels of α- and ω-muricholic acids were higher in rats fed LM as compared to HM pectin or the control diet. The inflammatory marker LBP was downregulated in rats fed medium-MW guar gum and HM pectin; these two fibers decreased the cecal abundance of Oscillospira and an unclassified genus in Ruminococcaceae, and increased that of an unclassified family in RF32. These results indicate that the molecular properties of guar gum and pectin are important for their ability to modulate cecal BA formation, gut microbiota composition, and high-fat diet induced inflammation. PMID:27315087

Plasmatic antioxidant capacity due to ascorbate using TEMPO scavenging and electron spin resonance.

PubMed

Piehl, Lidia L; Facorro, Graciela B; Huarte, Mónica G; Desimone, Martín F; Copello, Guillermo J; Díaz, Luis E; de Celis, Emilio Rubín

2005-09-01

Ascorbate is the most effective water-soluble antioxidant and its plasma concentration is usually measured by different methods including colorimetric assays, HPLC or capillary electrophoresis. Plasma antioxidant capacity is determined by indexes such as total reactive antioxidant potential, total antioxidant reactivity, oxygen radical absorbance capacity, etc. We developed an alternative method for the evaluation of the plasma antioxidant status due to ascorbate. TEMPO kinetics scavenging analyzed by ESR spectroscopy was performed on plasma samples in different antioxidant situations. Plasma ascorbate concentrations were determined by capillary electrophoresis. Ascorbyl radical levels were measured by ESR. Plasma reactivity with TEMPO (PR-T) reflected plasma ascorbate levels. Average PR-T for normal plasmas resulted 85+/-27 micromol/l (n=43). PR-T during ascorbic acid intake (1 g/day) increased to an average value of 130+/-20 micromol/l (p<0.001, n=20). PR-T correlated with the plasmatic ascorbate levels determined by capillary electrophoresis (r=0.92), presenting as an advantage the avoiding of the deproteination step. Plasma ascorbyl radical levels increase from 16+/-2 to 24+/-3 nmol/l (p<0.005, n=14) after ascorbate intake. PR-T could be considered as a measure of the plasmatic antioxidant capacity due to the plasma ascorbate levels and could be useful to investigate different antioxidant situations.

Relationships between serum brain-derived neurotrophic factor, plasma catecholamine metabolites, cytokines, cognitive function and clinical symptoms in Japanese patients with chronic schizophrenia treated with atypical antipsychotic monotherapy.

PubMed

Hori, Hikaru; Yoshimura, Reiji; Katsuki, Asuka; Atake, Kiyokazu; Igata, Ryohei; Konishi, Yuki; Nakamura, Jun

2017-08-01

Catecholamines, brain-derived neurotrophic factor (BDNF) and cytokines may be involved in the pathophysiology of schizophrenia. The aim of this study was to examine the associations between serum BDNF levels, plasma catecholamine metablolites, cytokines and the cognitive functions of patients with schizophrenia treated with atypical antipsychotic monotherapy. One hundred and forty-six patients with schizophrenia and 51 age- and sex-matched healthy controls were examined for peripheral biological markers and neurocognitive test. There were positive correlations between serum BDNF levels and scores for verbal memory and attention and processing speed as well as between serum BDNF levels and negative symptoms. Furthermore, there was a negative correlation between the plasma homovanillic acid (HVA) level and motor function and a positive correlation between the plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) level and attention and processing speed. There were no significant correlations between interleukin-6 or tumour necrosis factor alpha and cognitive function. Moreover, there were no significant correlations between the plasma levels of HVA, MHPG, cytokines and clinical symptoms. Serum BDNF levels are positively related to the impairment of verbal memory and attention, plasma HVA levels are positively related to motor function, and plasma MHPG levels are positively related to attention in patients with schizophrenia.

Caveolin-1 is required for fatty acid translocase (FAT/CD36) localization and function at the plasma membrane of mouse embryonic fibroblasts.

PubMed

Ring, Axel; Le Lay, Soazig; Pohl, Juergen; Verkade, Paul; Stremmel, Wolfgang

2006-04-01

Several lines of evidence suggest that lipid rafts are involved in cellular fatty acid uptake and influence fatty acid translocase (FAT/CD36) function. However, it remains unknown whether caveolae, a specialized raft type, are required for this mechanism. Here, we show that wild-type (WT) mouse embryonic fibroblasts (MEFs) and caveolin-1 knockout (KO) MEFs, which are devoid of caveolae, have comparable overall expression of FAT/CD36 protein but altered subcellular FAT/CD36 localization and function. In WT MEFs, FAT/CD36 was isolated with both lipid raft enriched detergent-resistant membranes (DRMs) and detergent-soluble membranes (DSMs), whereas in cav-1 KO cells it was exclusively associated with DSMs. Subcellular fractionation demonstrated that FAT/CD36 in WT MEFs was localized intracellularly and at the plasma membrane level while in cav-1 KO MEFs it was absent from the plasma membrane. This mistargeting of FAT/CD36 in cav-1 KO cells resulted in reduced fatty acid uptake compared to WT controls. Adenoviral expression of caveolin-1 in KO MEFs induced caveolae formation, redirection of FAT/CD36 to the plasma membrane and rescue of fatty acid uptake. In conclusion, our data provide evidence that caveolin-1 is necessary to target FAT/CD36 to the plasma membrane. Caveolin-1 may influence fatty acid uptake by regulating surface availability of FAT/CD36.

Lipogenesis and lipid peroxidation in rat testes after long-term treatment with sucrose and tannic acid in drinking water.

PubMed

Mašek, T; Starčević, K

2017-05-01

We studied the influence of long-term treatment with sucrose and tannic acid in drinking water on the fatty acid profile and lipid peroxidation in rat testes. Male Wistar rats were supplemented with sucrose (30% w/v) or with sucrose and tannic acid (sucrose 30% w/v, tannic acid 0.1% w/v) in drinking water. The treatment with sucrose elevated blood glucose levels in the plasma (p < .05) and decreased the testis weight (p < .05) and testis index (p < .05) of the rats. Sucrose treatment increased monounsaturated fatty acids (MUFA) and C22:6n3, and decreased n6 fatty acids in testis tissue. Lipid peroxidation was significantly increased after sucrose administration in plasma (p < .05) and testis tissue (p < .01). The addition of tannic acid led to the decrease in lipid peroxidation in the plasma (p < .05) and testis (p < .05), a further increase in MUFA and decrease in n6 fatty acids. In conclusion, sucrose significantly altered the testis fatty acid profile with an increase in MUFA and C22:6n3, and a decrease in n6 fatty acids. Tannic acid attenuated oxidative stress and hyperglycaemia, but it did not improve pathological changes in the fatty acid composition of the testis. © 2016 Blackwell Verlag GmbH.

Association between plasma endocannabinoids and appetite in hemodialysis patients: a pilot study

USDA-ARS?s Scientific Manuscript database

Weight loss is a well-recognized complication in subjects undergoing hemodialysis for impaired kidney function. This pilot study explored whether plasma levels of compounds known to mediate appetite, the endocannabinoids (EC) and EC-like compounds derived from polyunsaturated fatty acids (PUFA), ar...

Efficacy of docosahexaenoic acid-enriched formula to enhance maternal and fetal blood docosahexaenoic acid levels: Randomized double-blinded placebo-controlled trial of pregnant women with gestational diabetes mellitus.

PubMed

Min, Yoeju; Djahanbakhch, Ovrang; Hutchinson, Joanne; Eram, Sofia; Bhullar, Amritpal S; Namugere, Irene; Ghebremeskel, Kebreab

2016-06-01

Gestational diabetes mellitus (GDM) compromises the level of docosahexaenoic acid (DHA) in phospholipids of maternal and fetal red blood cells and fetal plasma. This is of some concern because of the importance of DHA for fetal neuro-visual development. We have investigated whether this abnormality could be rectified by supplementation with DHA-enriched formula. Women with GDM (n = 138) recruited from Newham University Hospital, London received two capsules of DHA-enriched formula (active-group) or high oleic acid sunflower seed oil (placebo-group) from diagnosis until delivery. Maternal (baseline and delivery) and fetal (cord blood) red blood cell and plasma phospholipid fatty acid composition, and neonatal anthropometry were assessed. One hundred and fourteen women (58 active, 56 placebo) completed the trial. The active-group compared with the placebo-group had significantly enhanced level of DHA in plasma phosphatidylcholine (4.5% vs 3.8%, P = 0.011), red blood cell phosphatidylcholine (2.7% vs 2.2%, P = 0.022) and phosphatidylethoanolamine (9.5% vs 7.6%, P = 0.002). There was no difference in cord plasma and red blood cell phospholipid DHA between the two groups. The neonates of the two groups of women had comparable anthropometric measurements at birth. Daily supplementation of 600 mg DHA enhances maternal but not fetal DHA status in pregnancy complicated by GDM. The inefficacy of the supplement to improve fetal status suggests that the transfer of DHA across the placenta maybe impaired in women with the condition. Regardless of the mechanisms responsible for the impairment of the transfer, the finding has implications for the management of neonates of women with GDM because they are born with a reduced level of DHA and the condition is thought to be associated with a risk of neuro-developmental deficits. We suggest that babies of women with GDM, particularly those not suckling, similar to the babies born prematurely require formula milk fortified with a higher level of DHA. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Study of the protective effect of ascorbic acid against the toxicity of stannous chloride on oxidative damage, antioxidant enzymes and biochemical parameters in rabbits.

PubMed

Yousef, M I; Awad, T I; Elhag, F A; Khaled, F A

2007-06-25

Stannous chloride (SnCl2) is a reducing chemical agent used in several man-made products. SnCl2 can generate reactive oxygen species (ROS). Therefore, the present study has been carried out to investigate the antioxidant action of l-ascorbic acid (AA) in minimizing SnCl2 toxicity on lipid peroxidation, antioxidant enzyme, and biochemical parameters in male New Zealand white rabbits. Animals were assigned to one of four treatment groups: 0mg AA and 0mg SnCl2/kg BW (control); 40 mg AA/kg BW; 20mg SnCl2/kg BW; 20mg SnCl2 plus 40 mg AA/kg BW. Rabbits were orally administered the respective doses every other day for 12 weeks. Results obtained showed that SnCl2 significantly (P<0.05) induced thiobarbituric acid-reactive substances (TBARS; the marker of lipid peroxidation) in plasma, while the activities of glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT), and the level of sulfhydryl groups (SH-group) were decreased (P<0.05) in blood plasma. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (AlP), acid phosphatase (AcP) and lactate dehydrogenase (LDH) activities were decreased (P<0.05). Stannous chloride significantly (P<0.05) increased the levels of plasma total lipid (TL), cholesterol, triglyceride (TG), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), glucose, urea and total bilirubin. On the other hand, the level of plasma high-density lipoprotein (HDL), total protein (TP), albumin (A) and globulin (G) were significantly (P<0.05) decreased. Ascorbic acid alone significantly decreased the levels of TBARS, lipids and urea, and increased the activities of GST, SOD and CAT, and the levels of SH-group and proteins. While the rest of the tested parameters were not affected. Also, the presence of AA with SnCl2 alleviated its harmful effects on most of the tested parameters. Therefore, the present results revealed that treatment with AA could minimize the toxic effects of stannous chloride.

Influence of medium-chain triglycerides on lipid metabolism in the rat.

PubMed

Leveille, G A; Pardini, R S; Tillotson, J A

1967-07-01

Lipid metabolism was studied in rats fed diets containing corn oil, coconut oil, or medium-chain triglyceride (MCT), a glyceride mixture containing fatty acids of 8 and 10 carbons in length. The ingestion of MCT-supplemented, cholesterolfree diets depressed plasma and liver total lipids and cholesterol as compared with corn oil-supplemented diets. In rats fed cholesterol-containing diets, plasma cholesterol levels were not influenced by dietary MCT, but liver cholesterol levels were significantly lower than in animals fed corn oil. In vitro cholesterol synthesis from acetate-1-(14)C was lower in liver slices of rats that consumed MCT than in similar preparations from corn oil-fed rats. Studies of fatty acid carboxyl labeling from acetate-1-(14)C and the conversion of palmitate-1-(14)C to C(18) acids by liver slices showed that chain-lengthening activity is greater in the liver tissue of rats fed MCT than in the liver of animals fed corn oil. The hepatic fatty acid desaturation mechanisms, evaluated by measuring the conversion of stearate-2-(14)C to oleate, was also enhanced by feeding MCT.Adipose tissue of rats fed MCT converts acetate-1-(14)C to fatty acids at a much faster rate than does tissue from animals fed corn oil. Evidence is presented to show that the enhanced incorporation of acetate into fatty acids by the adipose tissue of rats fed MCT represents de novo synthesis of fatty acids and not chain-lengthening activity. Data are also presented on the fatty acid composition of plasma, liver, and adipose tissue lipids of rats fed the different fats under study.

EICOSAPENTAENOIC ACID ENHANCES HEATSTROKE-IMPAIRED INTESTINAL EPITHELIAL BARRIER FUNCTION IN RATS.

PubMed

Xiao, Guizhen; Yuan, Fangfang; Geng, Yan; Qiu, Xiaowen; Liu, Zhifeng; Lu, Jiefu; Tang, Liqun; Zhang, Yali; Su, Lei

2015-10-01

Dysfunction of the intestinal barrier plays an important role in the pathological process of heatstroke. Omega-3 (or n-3) polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), help protect the intestinal mucosal barrier. This study assessed if pretreating rats with EPA or DHA could alleviate heat stress-induced damage to the intestinal barrier caused by experimental heatstroke. Male Wistar rats were pregavaged with either EPA, DHA, corn oil, or normal saline (all 1 g/kg) for 21 days before the heatstroke experiment (control rats were not exposed to heat). Experimental rats were exposed to an ambient temperature of 37°C and 60% humidity to induce heatstroke, and then they were allowed to recover at room temperature after rapid cooling. Survival time of rats was monitored after heatstroke. Horseradish peroxidase flux from the gut lumen and the level of plasma D-lactate were measured to analyze intestinal permeability at 6 h after heatstroke. Plasma endotoxin levels were determined using a limulus amoebocyte lysate assay. Expressions of the tight junction (TJ) proteins occludin and ZO-1 were analyzed by Western blot and localized by immunofluorescence microscopy. Tight junction protein morphology was observed by transmission electron microscopy. Fatty acids of ileal mucosa were analyzed using gas chromatography-mass selective detector. Eicosapentaenoic acid significantly increased survival time after heatstroke. Eicosapentaenoic acid significantly decreased intestinal permeability and plasma endotoxin levels. Eicosapentaenoic acid effectively attenuated the heatstroke-induced disruption of the intestinal structure and improved the histology score, whereas DHA was less effective, and corn oil was ineffective. Pretreatment with EPA also increased expression of occludin and ZO-1 to effectively prevent TJ disruption. Eicosapentaenoic acid pretreatment enriched itself in the membrane of intestinal cells. Our results indicate that EPA pretreatment is more effective than DHA pretreatment in attenuating heat-induced intestinal dysfunction and preventing TJ damage. Enhanced expression of TJ proteins that support the epithelial barrier integrity may be important for maintaining a functional intestinal barrier during heatstroke.

Plasma homovanillic acid in the prodromal phase of schizophrenia.

PubMed

Sumiyoshi, T; Kurachi, M; Kurokawa, K; Yotsutsuji, T; Uehara, T; Itoh, H; Saitoh, O

2000-03-01

Plasma levels of homovanillic acid (pHVA) have been used as a peripheral measure of central dopaminergic activity. Despite a large body of studies investigating pHVA in schizophrenia, little is known about pHVA in patients in the prodromal phase of the illness. Plasma HVA levels of 12 male outpatients meeting DSM-III-R criteria for the prodromal phase of schizophrenia at the time of blood sampling (who later developed psychotic symptoms) were compared with those of 12 normal male healthy volunteers. Task amounts in the Kraepelin arithmetic test at the time of blood sampling were compared between the prodromal patients and normal controls and were correlated with pHVA levels. The prodromal patients had significantly higher pHVA levels compared with normal control subjects. The mean amount of the arithmetic task for the prodromal patients was significantly less than that for controls. In the patient group, a significant negative correlation was observed between pHVA levels and the task amounts. Data from the present study indicate the presence of dopaminergic dysfunction in the prodromal stage of schizophrenia that is associated with neuropsychological impairment. Increased pHVA levels in the prodromal patients may have implications for early detection of schizophrenia.

Circulating irisin and glucose metabolism in overweight/obese women: effects of α-lipoic acid and eicosapentaenoic acid.

PubMed

Huerta, A E; Prieto-Hontoria, P L; Fernández-Galilea, M; Sáinz, N; Cuervo, M; Martínez, J A; Moreno-Aliaga, M J

2015-09-01

Irisin is a myokine/adipokine with potential role in obesity and diabetes. The objectives of the present study were to analyse the relationship between irisin and glucose metabolism at baseline and during an oral glucose tolerance test (OGTT) and to determine the effects of eicosapentaenoic acid (EPA) and/or α-lipoic acid treatment on irisin production in cultured human adipocytes and in vivo in healthy overweight/obese women following a weight loss program. Seventy-three overweight/obese women followed a 30% energy-restricted diet supplemented without (control) or with EPA (1.3 g/day), α-lipoic acid (0.3 g/day) or both EPA + α-lipoic acid (1.3 + 0.3 g/day) during 10 weeks. An OGTT was performed at baseline. Moreover, human adipocytes were treated with EPA (100-200 μM) or α-lipoic acid (100-250 μM) during 24 h. At baseline plasma, irisin circulating levels were positively associated with glucose levels; however, serum irisin concentrations were not affected by the increment in blood glucose or insulin during the OGTT. Treatment with α-lipoic acid (250 μM) upregulated Fndc5 messenger RNA (mRNA) and irisin secretion in cultured adipocytes. In overweight/obese women, irisin circulating levels decreased significantly after weight loss in all groups, while no additional differences were induced by EPA or α-lipoic acid supplementation. Moreover, plasma irisin levels were positively associated with higher glucose concentrations at beginning and at endpoint of the study. The data from the OGTT suggest that glucose is not a direct contributing factor of irisin release. The higher irisin levels observed in overweight/obese conditions could be a protective response of organism to early glucose impairments.

The effects of dietary boron compounds in supplemented diet on hormonal activity and some biochemical parameters in rats.

PubMed

Kucukkurt, Ismail; Akbel, Erten; Karabag, Funda; Ince, Sinan

2015-03-01

The aims of this study were to clarify the effects of dietary boric acid or borax, as a boron (B) source, on hormonal status (leptin, insulin, triiodothyronine (T3), and thyroxine) and some biochemical parameter levels as glucose, carnitine, nonesterified fatty acids, and betahydroxybutyric acid in rats. A total of 30 Sprague-Dawley male rats were divided into three equal groups: the animals in the first group (control) were fed with a standard rodent diet containing 6.4 mg B/kg, and the animals in the experimental group were fed with a standard rodent diet added with boric acid and borax (100 mg B/kg) throughout the experimental period of 28 days. The B compounds especially borax decreased leptin, insulin, and glucose levels, whereas increased T3 and carnitine levels in plasma. In addition, body weight of rats was found to be low in the boric acid group at the end of 4 weeks. Consequently, our results demonstrate that B supplementation (100 mg/kg) in diet decreases body weight, leptin, and insulin, whereas increases T3 levels in plasma, so enhances the metabolic activity of rats. Between the B compounds used in this study, it was found that borax had a greater effect on hormonal status than boric acid. © The Author(s) 2012.

Serum trans-fatty acids level are positively associated with lower food security among american adults.

PubMed

Mazidi, Mohsen; Vatanparast, Hassan

2018-03-07

In the current study we aimed to assess whether the food security is associated with serum trans-fatty acids (TFAs) and dietary fat. Analyses were restricted to participants (from the US National Health and Nutrition Examination Survey) with data available on serum and diet TFAs and food security status from 2009 to 2010. All statistical analyses (analysis of covariance and linear regression) accounted for the survey design and sample weights. We included 3876 participants, overall (48.6%) participants were men, and (51.4%) were women, generally (69.0%) had high food security. Subjects with higher food security had a higher level of education as well (p < 0.001). Age-adjusted, sex-adjusted, race-adjusted, education-adjusted mean of trans 9-octadecenoic acid and trans-9, trans-12-octadecadienoic acid were higher in plasma of participants with lower food security (all p < 0.001), moreover in same model there was a significant positive association between plasma level of trans-11-octadecenoic acid, trans-9-octadecenoic acid and trans-9, trans-12-octadecadienoic acid and score of food security. Further, age, sex, race, education, and energy intake adjusted mean of dietary fatty acids show that total polyunsaturated fatty acids are higher in subjects with higher food security (p = 0.026) while, cholesterol consumption is higher in subjects with lower food security (p = 0.039). Our findings provide more evidence on the association between food insecurity and the higher level of TFAs in serum and different type of fat in the diet.

Silver ions increase plasma membrane permeability through modulation of intracellular calcium levels in tobacco BY-2 cells.

PubMed

Klíma, Petr; Laňková, Martina; Vandenbussche, Filip; Van Der Straeten, Dominique; Petrášek, Jan

2018-05-01

Silver ions increase plasma membrane permeability for water and small organic compounds through their stimulatory effect on plasma membrane calcium channels, with subsequent modulation of intracellular calcium levels and ion homeostasis. The action of silver ions at the plant plasma membrane is largely connected with the inhibition of ethylene signalling thanks to the ability of silver ion to replace the copper cofactor in the ethylene receptor. A link coupling the action of silver ions and cellular auxin efflux has been suggested earlier by their possible direct interaction with auxin efflux carriers or by influencing plasma membrane permeability. Using tobacco BY-2 cells, we demonstrate here that besides a dramatic increase of efflux of synthetic auxins 2,4-dichlorophenoxyacetic acid (2,4-D) and 1-naphthalene acetic acid (NAA), treatment with AgNO 3 resulted in enhanced efflux of the cytokinin trans-zeatin (tZ) as well as the auxin structural analogues tryptophan (Trp) and benzoic acid (BA). The application of AgNO 3 was accompanied by gradual water loss and plasmolysis. The observed effects were dependent on the availability of extracellular calcium ions (Ca 2+ ) as shown by comparison of transport assays in Ca 2+ -rich and Ca 2+ -free buffers and upon treatment with inhibitors of plasma membrane Ca 2+ -permeable channels Al 3+ and ruthenium red, both abolishing the effect of AgNO 3 . Confocal microscopy of Ca 2+ -sensitive fluorescence indicator Fluo-4FF, acetoxymethyl (AM) ester suggested that the extracellular Ca 2+ availability is necessary to trigger the response to silver ions and that the intracellular Ca 2+ pool alone is not sufficient for this effect. Altogether, our data suggest that in plant cells the effects of silver ions originate from the primal modification of the internal calcium levels, possibly by their interaction with Ca 2+ -permeable channels at the plasma membrane.

The effect of leg hyperthermia using far infrared rays in bedridden subjects with type 2 diabetes mellitus.

PubMed

Kawaura, Akihiko; Tanida, Noritoshi; Kamitani, Masato; Akiyama, Junichi; Mizutani, Masatoshi; Tsugawa, Naoko; Okano, Toshio; Takeda, Eiji

2010-04-01

We examined the effect of leg hyperthermia on oxidative stress in bedridden subjects with type 2 diabetes mellitus using 15-min sessions of far infrared rays over a two-week period. Four subjects (male 1, female 3) incapacitated by a stroke were recruited for this study. All patients were admitted to Takahashi Central Hospital and ate the same hospital meals. Fasting plasma glucose, HbA1c, tumor necrosis factor (TNF)alpha, free fatty acid, leptin, adiponectin and plasma 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) levels as a marker of oxidative stress were measured on admission, just before and 2 weeks after local heating of the leg. Results showed that plasma total 8-epi-PGF2alpha levels were decreased significantly while TNFalpha levels were increased significantly. On the other hand, glucose, HbA1c, free fatty acid, leptin and adiponectin levels were not changed during the study period. These results suggest that repeated leg hyperthermia may protect against oxidative stress.

Effect of long-term exposure to pesticides on plasma esterases from plastic greenhouse workers.

PubMed

Hernández, Antonio; Gómez, M Amparo; Pena, Gloria; Gil, Fernando; Rodrigo, Lourdes; Villanueva, Enrique; Pla, Antonio

2004-07-23

Previous reports in animals considered beta-glucuronidase activity as a novel biomarker of anticholinesterase (organophosphates and carbamates) pesticides exposure. Acid phosphatase activity was also shown to increase after organophosphates exposure. In addition, there is evidence that the paraoxonase status influences sensitivity to specific pesticides. In this study, activities of beta-glucuronidase, acid phosphatase, cholinesterase, and paraoxonase were measured in plasma from plastic greenhouse workers exposed over the long term to different pesticides, including organophosphates and carbamates, in order to evaluate the potential chronic toxicity of pesticides at occupational level. Our results show that activities of paraoxonase and cholinesterase were decreased in applicators of pesticides compared to non-applicators. Likewise, it was found that activities of beta-glucuronidase and acid phosphatase were associated with pesticide exposure in humans, and that both biochemical parameters were related to each other. Interestingly, the paraoxonase B allele (phenotyped in plasma) was associated with a higher risk of inhibition of cholinesterase activity above a 25% level, which supports the hypothesis that paraoxonase phenotypes are associated with susceptibility of humans to anticholinesterase pesticides toxicity. Copyright Taylor and Francis Inc.

Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats.

PubMed

Qin, B; Polansky, M M; Anderson, R A

2010-03-01

We reported earlier that dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we have examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molecular mechanisms of CE in epididymal adipose tissue (EAT). In Wistar rats fed a high-fructose diet (HFD) to induce insulin resistance, supplementation with a CE (Cinnulin PF, 50 mg/kg daily) for 8 weeks reduced blood glucose, plasma insulin, triglycerides, total cholesterol, chylomicron-apoB48, VLDL-apoB100, and soluble CD36. CE also inhibited plasma retinol binding protein 4 (RBP4) and fatty acid binding protein 4 (FABP4) levels. CE-induced increases in plasma adiponectin were not significant. CE did not affect food intake, bodyweight, and EAT weight. In EAT, there were increases in the insulin receptor ( IR) and IR substrate 2 ( IRS2) mRNA, but CE-induced increases in mRNA expression of IRS1, phosphoinositide-3-kinase, AKT1, glucose transporters 1 and 4 , and glycogen synthase 1 expression and decreased trends in mRNA expression of glycogen synthase kinase 3beta were not statistically significant. CE also enhanced the mRNA levels of ADIPOQ, and inhibited sterol regulatory element binding protein-1c mRNA levels. mRNA and protein levels of fatty acid synthase and FABP4 were inhibited by CE and RBP4, and CD36 protein levels were also decreased by CE. These results suggest that CE effectively ameliorates circulating levels of adipokines partially mediated via regulation of the expression of multiple genes involved in insulin sensitivity and lipogenesis in the EAT.

Expression of the Aspergillus terreus itaconic acid biosynthesis cluster in Aspergillus niger

PubMed Central

2014-01-01

Background Aspergillus terreus is a natural producer of itaconic acid and is currently used to produce itaconic acid on an industrial scale. The metabolic process for itaconic acid biosynthesis is very similar to the production of citric acid in Aspergillus niger. However, a key enzyme in A. niger, cis-aconitate decarboxylase, is missing. The introduction of the A. terreus cadA gene in A. niger exploits the high level of citric acid production (over 200 g per liter) and theoretically can lead to production levels of over 135 g per liter of itaconic acid in A. niger. Given the potential for higher production levels in A. niger, production of itaconic acid in this host was investigated. Results Expression of Aspergillus terreus cis-aconitate decarboxylase in Aspergillus niger resulted in the production of a low concentration (0.05 g/L) of itaconic acid. Overexpression of codon-optimized genes for cis-aconitate decarboxylase, a mitochondrial transporter and a plasma membrane transporter in an oxaloacetate hydrolase and glucose oxidase deficient A. niger strain led to highly increased yields and itaconic acid production titers. At these higher production titers, the effect of the mitochondrial and plasma membrane transporters was much more pronounced, with levels being 5–8 times higher than previously described. Conclusions Itaconic acid can be produced in A. niger by the introduction of the A. terreus cis-aconitate decarboxylase encoding cadA gene. This results in a low itaconic acid production level, which can be increased by codon-optimization of the cadA gene for A. niger. A second crucial requirement for efficient production of itaconic acid is the expression of the A. terreus mttA gene, encoding a putative mitochondrial transporter. Expression of this transporter results in a twenty-fold increase in the secretion of itaconic acid. Expression of the A. terreus itaconic acid cluster consisting of the cadA gene, the mttA gene and the mfsA gene results in A. niger strains that produce over twenty five-fold higher levels of itaconic acid and show a twenty-fold increase in yield compared to a strain expressing only CadA. PMID:24438100

Expression of the Aspergillus terreus itaconic acid biosynthesis cluster in Aspergillus niger.

PubMed

van der Straat, Laura; Vernooij, Marloes; Lammers, Marieke; van den Berg, Willy; Schonewille, Tom; Cordewener, Jan; van der Meer, Ingrid; Koops, Andries; de Graaff, Leo H

2014-01-17

Aspergillus terreus is a natural producer of itaconic acid and is currently used to produce itaconic acid on an industrial scale. The metabolic process for itaconic acid biosynthesis is very similar to the production of citric acid in Aspergillus niger. However, a key enzyme in A. niger, cis-aconitate decarboxylase, is missing. The introduction of the A. terreus cadA gene in A. niger exploits the high level of citric acid production (over 200 g per liter) and theoretically can lead to production levels of over 135 g per liter of itaconic acid in A. niger. Given the potential for higher production levels in A. niger, production of itaconic acid in this host was investigated. Expression of Aspergillus terreus cis-aconitate decarboxylase in Aspergillus niger resulted in the production of a low concentration (0.05 g/L) of itaconic acid. Overexpression of codon-optimized genes for cis-aconitate decarboxylase, a mitochondrial transporter and a plasma membrane transporter in an oxaloacetate hydrolase and glucose oxidase deficient A. niger strain led to highly increased yields and itaconic acid production titers. At these higher production titers, the effect of the mitochondrial and plasma membrane transporters was much more pronounced, with levels being 5-8 times higher than previously described. Itaconic acid can be produced in A. niger by the introduction of the A. terreus cis-aconitate decarboxylase encoding cadA gene. This results in a low itaconic acid production level, which can be increased by codon-optimization of the cadA gene for A. niger. A second crucial requirement for efficient production of itaconic acid is the expression of the A. terreus mttA gene, encoding a putative mitochondrial transporter. Expression of this transporter results in a twenty-fold increase in the secretion of itaconic acid. Expression of the A. terreus itaconic acid cluster consisting of the cadA gene, the mttA gene and the mfsA gene results in A. niger strains that produce over twenty five-fold higher levels of itaconic acid and show a twenty-fold increase in yield compared to a strain expressing only CadA.

Furan fatty acids - Beneficial or harmful to health?

PubMed

Xu, Long; Sinclair, Andrew J; Faiza, Muniba; Li, Daoming; Han, Xianlin; Yin, Huiyong; Wang, Yonghua

2017-10-01

Furan fatty acids are found in plants, algae, and fish, and reported to have some positive health benefits, including anti-oxidant and anti-inflammatory activities, and inhibition of non-enzymatic lipid peroxidation. A major metabolite of furan fatty acids, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), has been reported to be increased in patients who progress from prediabetes to type 2 diabetes, although CMPF is not necessarily associated with impaired glucose metabolism. Other studies report that CMPF levels are lower in subjects with diabetes than control subjects. Plasma CMPF levels increase in subjects who consume fish or fish oil, and in patients with renal failure. It is not known where furan fatty acids are converted to CMPF and it is speculated that this might be a result of microbiome activity. The plasma levels reported for CMPF in healthy, diabetic and patients with renal disease vary by factors of more than 100-fold within each of these three groups, so measurement error appears to be limiting the ability to interpret studies. This review explores these controversies and raises questions about whether CMPF is a marker for healthy diets or indeed associated with diabetes and renal health. The review concludes that, on balance, furan fatty acids are beneficial for health. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of folic acid levels in schizophrenic patients and control groups

NASA Astrophysics Data System (ADS)

Arthy, C. C.; Amin, M. M.; Effendy, E.

2018-03-01

Folic acid deficiency is a risk factor for schizophrenia through epidemiology, biochemistry and gene-related studies. Compared with healthy people, schizophrenic patients may have high homocysteine plasma values and homocysteine or low levels of folic acid, which seems to correlate with extrapyramidal motor symptoms caused by neuroleptic therapy and with symptoms of schizophrenia. In this present study, we focus on the difference of folic acid level between schizophrenic patient and control group. The study sample consisted of schizophrenic patients and 14 people in the control group and performed blood sampling to obtain the results of folic acid levels. The folic acid level in both groups was within normal range, but the schizophrenic patient group had lower mean folic acid values of 5.00 ng/ml (sb 1.66), compared with the control group with mean folic acid values of 10.75 ng/ml (sb 4.33). there was the group of the control group had a higher value of folic acid than the schizophrenic group.

A role for PPARα in the regulation of arginine metabolism and nitric oxide synthesis.

PubMed

Guelzim, Najoua; Mariotti, François; Martin, Pascal G P; Lasserre, Frédéric; Pineau, Thierry; Hermier, Dominique

2011-10-01

The pleiotropic effects of PPARα may include the regulation of amino acid metabolism. Nitric oxide (NO) is a key player in vascular homeostasis. NO synthesis may be jeopardized by a differential channeling of arginine toward urea (via arginase) versus NO (via NO synthase, NOS). This was studied in wild-type (WT) and PPARα-null (KO) mice fed diets containing either saturated fatty acids (COCO diet) or 18:3 n-3 (LIN diet). Metabolic markers of arginine metabolism were assayed in urine and plasma. mRNA levels of arginases and NOS were determined in liver. Whole-body NO synthesis and the conversion of systemic arginine into urea were assessed by using (15)N(2)-guanido-arginine and measuring urinary (15)NO(3) and [(15)N]-urea. PPARα deficiency resulted in a markedly lower whole-body NO synthesis, whereas the conversion of systemic arginine into urea remained unaffected. PPARα deficiency also increased plasma arginine and decreased citrulline concentration in plasma. These changes could not be ascribed to a direct effect on hepatic target genes, since NOS mRNA levels were unaffected, and arginase mRNA levels decreased in KO mice. Despite the low level in the diet, the nature of the fatty acids modulated some effects of PPARα deficiency, including plasma arginine and urea, which increased more in KO mice fed the LIN diet than in those fed the COCO diet. In conclusion, PPARα is largely involved in normal whole-body NO synthesis. This warrants further study on the potential of PPARα activation to maintain NO synthesis in the initiation of the metabolic syndrome.

Enhanced high-performance liquid chromatography method for the determination of retinoic acid in plasma. Development, optimization and validation.

PubMed

Teglia, Carla M; Gil García, María D; Galera, María Martínez; Goicoechea, Héctor C

2014-08-01

When determining endogenous compounds in biological samples, the lack of blank or analyte-free matrix samples involves the use of alternative strategies for calibration and quantitation. This article deals with the development, optimization and validation of a high performance liquid chromatography method for the determination of retinoic acid in plasma, obtaining at the same time information about its isomers, taking into account the basal concentration of these endobiotica. An experimental design was used for the optimization of three variables: mobile phase composition, flow rate and column temperature through a central composite design. Four responses were selected for optimization purposes (area under the peaks, quantity of peaks, analysis time and resolution between the first principal peak and the following one). The optimum conditions resulted in a mobile phase consisting of methanol 83.4% (v/v), acetonitrile 0.6% (v/v) and acid aqueous solution 16.0% (v/v); flow rate of 0.68 mL min(-1) and an column temperature of 37.10 °C. Detection was performed at 350 nm by a diode array detector. The method was validated following a holistic approach that included not only the classical parameters related to method performance but also the robustness and the expected proportion of acceptable results lying inside predefined acceptability intervals, i.e., the uncertainty of measurements. The method validation results indicated a high selectivity and good precision characteristics that were studied at four concentration levels, with RSD less than 5.0% for retinoic acid (less than 7.5% for the LOQ concentration level), in intra and inter-assay precision studies. Linearity was proved for a range from 0.00489 to 15.109 ng mL(-1) of retinoic acid and the recovery, which was studied at four different fortification levels in phuman plasma samples, varied from 99.5% to 106.5% for retinoic acid. The applicability of the method was demonstrated by determining retinoic acid and obtaining information about its isomers in human and frog plasma samples from different origins. Copyright © 2014 Elsevier B.V. All rights reserved.

Oxidants and anti-oxidants in turbot seminal plasma and their effects on sperm quality

NASA Astrophysics Data System (ADS)

Han, Mingming; Ding, Fuhong; Meng, Zhen; Lei, Jilin

2015-08-01

In this research, the concentration and activity of oxidants and anti-oxidants in turbot semen, and their effects on sperm quality were studied. The results showed that superoxide dismutase (SOD), catalase, glutathione reductase (GR), uric acid, vitamin E (VE) and vitamin C (VC) were more abundant in seminal plasma than in spermatozoa. The variation for each of them was specific. In seminal plasma, the activity of SOD and GR increased from November 15, November 30 to December 15, and then decreased on December 30. The concentrations of both VC and uric acid decreased during the first 3 sampling times and increased on December 30. The oxidants in seminal plasma accumulated to the highest on December 30. Lactic acid (LA) and ATP levels decreased to the lowest on December 30. The correlation analysis showed that GR had the significant positive relevance to sperm motility and VSL/VCL, while ·OH had negative relevance to them.

Homocysteine and disease: Causal associations or epiphenomenons?

PubMed

Hannibal, Luciana; Blom, Henk J

2017-02-01

Nutritional and genetic deficiencies of folate and vitamin B 12 lead to elevation of cellular homocysteine (Hcy), which translates in increased plasma Hcy. The sources and role of elevated plasma Hcy in pathology continues to be a subject of intense scientific debate. Whether a cause, mediator or marker, little is known about the molecular mechanisms and interactions of Hcy with cellular processes that lead to disease. The use of folic acid reduces the incidence of neural tube defects, but the effect of Hcy-lowering interventions with folic acid in cardiovascular disease and cognitive impairment remains controversial. The fact that levels of Hcy in plasma do not always reflect cellular status of this amino acid may account for the substantial gaps that exist between epidemiological, intervention and basic research studies. Understanding whether plasma Hcy is a mechanistic player or an epiphenomenon in pathogenesis requires further investigation, and this research is essential to improve the assessment and potential treatment of hyperhomocysteinemias. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship between absolute and relative ratios of glutamate, glutamine and GABA and severity of autism spectrum disorder.

PubMed

Al-Otaish, Hanoof; Al-Ayadhi, Laila; Bjørklund, Geir; Chirumbolo, Salvatore; Urbina, Mauricio A; El-Ansary, Afaf

2018-06-01

Autism spectrum disorder (ASD) is a neurodevelopmental pathology characterized by an impairment in social interaction, communication difficulties, and repetitive behaviors. Glutamate signaling abnormalities are thought to be considered as major etiological mechanisms leading to ASD. The search for amino-acidic catabolytes related to glutamate in patients with different levels of ASD might help current research to clarify the mechanisms underlying glutamate signaling and its disorders, particularly in relation to ASD. In the present study, plasma levels of the amino acids and their derivatives glutamate, glutamine, and γ-aminobutyric acid (GABA), associated with their relative ratios, were evaluated using an enzyme-linked immunosorbent assay (ELISA) technique in 40 male children with ASD and in 38 age- and gender-matched neurotypical health controls. The Social Responsiveness Scale (SRS) was used to evaluate social cognition, and the Childhood Autism Rating Scale (CARS) was used to assess subjects' behaviors. Children with ASD exhibited a significant elevation of plasma GABA and glutamate/glutamine ratio, as well as significantly lower levels of plasma glutamine and glutamate/GABA ratios compared to controls. No significant correlation was found between glutamate levels and the severity of autism, measured by CARS and SRS. In receiver operating characteristic (ROC) curve analysis, the area under the curve for GABA compared to other parameters was close to one, indicating its potential use as a biomarker. Glutamine appeared as the best predictive prognostic markers in the present study. The results of the present study indicate a disturbed balance between GABAergic and glutamatergic neurotransmission in ASD. The study also indicates that an increased plasma level of GABA can be potentially used as an early diagnostic biomarker for ASD.

Antioxidant defense and oxidative stress in children with acute hepatitis A

PubMed Central

Popovic-Dragonjic, Lidija; Jovanovic, Maja; Vrbic, Miodrag; Konstantinovic, Ljiljana; Kostic, Velimir; Dragonjic, Ivan

2011-01-01

BACKGROUND AND OBJECTIVES: Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients. DESIGN AND SETTING: Prospective, case-control study, over 2.5 years in patients under hospitalized and ambulatory care. PATIENTS AND METHODS: The levels of a whole-blood antioxidant, reduced glutathione; and plasma antioxidants, β-carotene, retinol, ascorbic acid, α-tocopherol; and the biomarker of oxidative stress, malondialdehyde, were evaluated in 50 pediatric patients (age range, 5-16 years; 29 males and 21 females) with acute hepatitis A and in 50 healthy children as control subjects (age range, 5-16 years; 25 males and 25 females). RESULTS: Plasma levels of reduced glutathione, β-carotene, retinol, α-tocopherol and ascorbic acid were significantly lower, while malondialdehyde plasma levels were significantly increased in the patient group when compared to the controls (P<.0001 for all parameters). CONCLUSIONS: Our findings show that pediatric patients with acute hepatitis A were influenced by oxidative stress, resulting in significantly lower levels of plasma antioxidants and increased lipid peroxidation. In the absence of other therapeutic options, antioxidant vitamin supplements could be added to the therapy for these patients to help reestablish the oxidant status balance. Further investigations to confirm this suggestion are recommended. PMID:21623054

Pretreatment plasma homovanillic acid in schizophrenia and schizoaffective disorder: the influence of demographic variables and the inpatient drug-free period.

PubMed

Sharma, R P; Javaid, J I; Davis, J M; Janicak, P G

1998-09-15

The relationship between plasma homovanillic acid (pHVA) and schizophrenic symptoms has not been conclusively determined. We reexamine pHVA levels in a new sample of patients with emphasis on demographic variables and the drug-free period. Plasma HVA levels were studied in 54 schizophrenic and schizoaffective-disordered, drug-free inpatients suffering from a psychotic exacerbation. A significant correlation was observed between pHVA levels and the number of inpatient drug-free days in the total sample, as well as the schizophrenic patient subsample. Further, pHVA was significantly and positively correlated with the duration of illness in the schizophrenic patient subsample. Plasma HVA correlations with behavior, as measured by Brief Psychiatric Rating Scale factors (anxiety/depression and hostility/suspiciousness), emerged only when considering schizophrenic patients drug-free for more than 2 weeks. No correlation was found between pHVA and the age of illness onset or the duration of the delay of treatment of the first psychotic episode. The effects of antipsychotic withdrawal on levels of pHVA in clinical populations may have to be examined and controlled for in future studies attempting to study the relationship between this metabolite and behavior in acutely ill, drug-free schizophrenic patients.

Plasma amino acid and urine organic acid profiles of Filipino patients with maple syrup urine disease (MSUD) and correlation with their neurologic features.

PubMed

Chiong, Mary Anne D; Tan, Marilyn A; Cordero, Cynthia P; Fodra, Esphie Grace D; Manliguis, Judy S; Lopez, Cristine P; Dalmacio, Leslie Michelle M

2016-12-01

Maple syrup urine disease (MSUD) is the most common inborn error of metabolism in the country. The cause of the neuropathology is still not well established although accumulation of branched chain amino acids (BCAA) and alteration in large neutral amino acids (LNAA) as well as energy deprivation are suggested. It is therefore the aim of this study to determine the plasma amino acid and urine organic acid profiles of patients with MSUD and correlate the findings with their neurologic features. Twenty six Filipino patients with MSUD were studied in terms of their plasma amino acid and urine organic acid profiles. Their results were compared with 26 age and sex matched controls. The neurologic features were correlated with the results of the plasma amino acids and urine organic acids. Majority of the patients with MSUD had developmental delay/intellectual disability (88%), speech delay (69%), and seizures (65%). Their amino acid profiles revealed low glutamine and alanine with high levels of leucine, isoleucine, phenylalanine, threonine and alloisoleucine compared to controls (p < 0.05). The urine organic acids showed significantly elevated excretion of the branched chain ketoacids and succinate (p < 0.05). However there were no biochemical markers that correlated significantly with the neurologic features. The findings suggest that there could still be altered LNAA metabolism among patients with MSUD when the BCAAs are elevated. Although the biochemical findings were not significantly correlated with the neurologic features, the study showed that prevention and avoidance of neurologic disturbances may still rely primarily on early diagnosis and prompt institution of treatment, along with strict compliance with the dietary regimen and maintenance of good metabolic control over time.

Metabolomic Analysis of Blood Plasma after Oral Administration of N-acetyl-d-Glucosamine in Dogs

PubMed Central

Osaki, Tomohiro; Kurozumi, Seiji; Sato, Kimihiko; Terashi, Taro; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

2015-01-01

N-acetyl-d-glucosamine (GlcNAc) is a monosaccharide that polymerizes linearly through (1,4)-β-linkages. GlcNAc is the monomeric unit of the polymer chitin. GlcNAc is a basic component of hyaluronic acid and keratin sulfate found on the cell surface. The aim of this study was to examine amino acid metabolism after oral GlcNAc administration in dogs. Results showed that plasma levels of ectoine were significantly higher after oral administration of GlcNAc than prior to administration (p < 0.001). To our knowledge, there have been no reports of increased ectoine concentrations in the plasma. The mechanism by which GlcNAc administration leads to increased ectoine plasma concentration remains unclear; future studies are required to clarify this mechanism. PMID:26262626

Postnatal development of plasma amino acids in hyperphagic rats.

PubMed

Salvadó, M J; Segués, T; Arola, L

1991-01-01

The effect of feeding a highly palatable high-energy cafeteria diet on individual amino acid levels in plasma during postnatal development of the rat has been evaluated and compared to chow-fed controls. The cafeteria diet selected by the rats was hypercaloric and hyperlipidic, with practically the same amount of carbohydrate as the control diet, and slightly hyperproteic. In response to cafeteria feeding, significant decreases were observed in plasma serine and cysteine along the period studied. Significant changes with age during the growth period were shown by cafeteria-fed animals, which were not observed in control rats. Citrulline levels were lower on days 10 and 14 in cafeteria pups than in chow pups. Methionine was highest on day 30. Threonine was also higher at days 20 and 30, as was valine but with a nadir at day 10. Lysine showed maximal values on days 14 and 30.

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

PubMed Central

2011-01-01

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

Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans.

PubMed

Vauzour, David; Tejera, Noemi; O'Neill, Colette; Booz, Valeria; Jude, Baptiste; Wolf, Insa M A; Rigby, Neil; Silvan, Jose Manuel; Curtis, Peter J; Cassidy, Aedin; de Pascual-Teresa, Sonia; Rimbach, Gerald; Minihane, Anne Marie

2015-03-01

Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Anthocyanins do not influence long-chain n-3 fatty acid status: studies in cells, rodents and humans☆

PubMed Central

Vauzour, David; Tejera, Noemi; O'Neill, Colette; Booz, Valeria; Jude, Baptiste; Wolf, Insa M.A.; Rigby, Neil; Silvan, Jose Manuel; Curtis, Peter J.; Cassidy, Aedin; de Pascual-Teresa, Sonia; Rimbach, Gerald; Minihane, Anne Marie

2015-01-01

Increased tissue status of the long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA), eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) is associated with cardiovascular and cognitive benefits. Limited epidemiological and animal data suggest that flavonoids, and specifically anthocyanins, may increase EPA and DHA levels, potentially by increasing their synthesis from the shorter-chain n-3 PUFA, α-linolenic acid. Using complimentary cell, rodent and human studies we investigated the impact of anthocyanins and anthocyanin-rich foods/extracts on plasma and tissue EPA and DHA levels and on the expression of fatty acid desaturase 2 (FADS2), which represents the rate limiting enzymes in EPA and DHA synthesis. In experiment 1, rats were fed a standard diet containing either palm oil or rapeseed oil supplemented with pure anthocyanins for 8 weeks. Retrospective fatty acid analysis was conducted on plasma samples collected from a human randomized controlled trial where participants consumed an elderberry extract for 12 weeks (experiment 2). HepG2 cells were cultured with α-linolenic acid with or without select anthocyanins and their in vivo metabolites for 24 h and 48 h (experiment 3). The fatty acid composition of the cell membranes, plasma and liver tissues were analyzed by gas chromatography. Anthocyanins and anthocyanin-rich food intake had no significant impact on EPA or DHA status or FADS2 gene expression in any model system. These data indicate little impact of dietary anthocyanins on n-3 PUFA distribution and suggest that the increasingly recognized benefits of anthocyanins are unlikely to be the result of a beneficial impact on tissue fatty acid status. PMID:25573539

Postprandial lipid responses to an alpha-linolenic acid-rich oil, olive oil and butter in women: A randomized crossover trial

PubMed Central

2011-01-01

Background Postprandial lipaemia varies with gender and the composition of dietary fat due to the partitioning of fatty acids between beta-oxidation and incorporation into triacylglycerols (TAGs). Increasing evidence highlights the importance of postprandial measurements to evaluate atherogenic risk. Postprandial effects of alpha-linolenic acid (ALA) in women are poorly characterized. We therefore studied the postprandial lipid response of women to an ALA-rich oil in comparison with olive oil and butter, and characterized the fatty acid composition of total lipids, TAGs, and non-esterified fatty acids (NEFAs) in plasma. Methods A randomized crossover design (n = 19) was used to compare the postprandial effects of 3 meals containing 35 g fat. Blood samples were collected at regular intervals for 7 h. Statistical analysis was carried out with ANOVA (significant difference = P < 0.05). Results No significant difference was seen in incremental area under the curve (iAUC) plasma-TAG between the meals. ALA and oleic acid levels were significantly increased in plasma after ALA-rich oil and olive oil meals, respectively. Palmitic acid was significantly increased in plasma-TAG after the butter meal. The ratios of 18:2 n-6 to18:3 n-3 in plasma-TAGs, three and seven hours after the ALA-rich oil meal, were 1.5 and 2.4, respectively. The corresponding values after the olive oil meal were: 13.8 and 16.9; and after the butter meal: 9.0 and 11.6. Conclusions The postprandial p-TAG and NEFA response in healthy pre-menopausal women was not significantly different after the intake of an ALA-rich oil, olive oil and butter. The ALA-rich oil significantly affected different plasma lipid fractions and improved the ratio of n-6 to n-3 fatty acids several hours postprandially. PMID:21711508

Evolution of plasma homovanillic acid (HVA) in chronic schizophrenic patients treated with haloperidol.

PubMed

Galinowski, A; Poirier, M F; Aymard, N; Leyris, A; Beauverie, P; Bourdel, M C; Loo, H

1998-06-01

In a 4-week study of 14 drug-free schizophrenic patients (according to DSM-III-R), free and conjugated fractions of plasma homovanillic acid (pHVA) were repeatedly measured. Free HVA levels decreased during the first 2 h of haloperidol intake (P < 0.03). Conjugated HVA levels slowly decreased during the following weeks (P < 0.05), while free HVA levels remained stable. After 4 weeks, free HVA levels remained unchanged 2 h after morning haloperidol intake, but conjugated HVA levels tended to increase. In haloperidol responders, at baseline the free/total HVA ratio was significantly higher than that in non-responders (P < 0.01). Tolerant patients, i.e. those whose post-treatment free HVA levels decreased below pre-treatment levels, were not found to respond better to haloperidol than non-tolerant patients. The balance between free and conjugated pHVA may be a better reflection of the action of haloperidol than free pHVA levels and it may be of prognostic value in terms of drug response.

[Synthesis and physico-chemical characterisation of some new derivatives of rutoside and clofibric acid].

PubMed

Lupaşcu, D; Profire, Lenuţa; Dănilă, Gh

2006-01-01

Fibrates are drugs with efficacy in reducing blood cholesterol levels and especially, triglyceride plasma levels. Unfortunately, fibrates have a poor water-solubility and showed some adverse reactions at long treatment. The objective of this study was to obtain some new clofibric acid derivatives with rutin; some of these compounds contain a guanidine moiety, known as effective at cardiovascular level. All the compounds are soluble in water.

Accumulation of 24S-hydroxycholesterol in neuronal SK-N-BE cells treated with hexacosanoic acid (C26:0): argument in favor of 24S-hydroxycholesterol as a potential biomarker of neurolipotoxicity.

PubMed

Zarrouk, A; Hammami, M; Moreau, T; Lizard, G

2015-02-01

Cholesterol oxide derivatives (oxysterols) are viewed as potential biomarkers of neurodegenerative diseases. 24S-hydroxycholesterol, an oxysterol produced only in brain neurons, is often found for unknown reasons in increased levels in the plasma in patients with neurodegenerative diseases. On human neuronal SK-N-BE cells treated with hexacosanoic acid (C26:0) identified at increased levels in the tissues and plasma of patients with peroxisomal leukodystrophies and Alzheimer's disease, we observed increased level of 24S-hydroxycholesterol associated with C26:0 induced lipotoxicity. This finding reinforces the hypothesis suggesting that 24S-hydroxycholesterol could constitute a biomarker of neurotoxicity. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Properties of zirconia after plasma treatment

NASA Astrophysics Data System (ADS)

Alekseenko, V. P.; Kulkov, S. N.

2017-09-01

The influence of high-frequency plasma treatment on the properties of zirconia powder is shown in the work. The powder was produced by a plasma-chemical method. The powders had a foamy form with the size of agglomerates of 5-10 μm and crystallites of 20-50 nm. The powders were treated by the pulse plasma unit with dielectric barrier discharge generator. It was shown that the plasma processing changes the acidity of water-powder suspensions from 8.1 to 4.3 pH, which signifies the powders' wettability improvement. It was revealed that more intensive mixing using ultrasound influences the acidity level, reducing it in comparison with mixing by paddle-type agitator. It was shown that these changes of surface properties have relaxation by 4% per day and extrapolation of this dependence shows that the powder will have initial properties after 400 hours storage at room conditions.

Chromium-induced membrane damage: protective role of ascorbic acid.

PubMed

Dey, S K; Nayak, P; Roy, S

2001-07-01

Importance of chromium as environmental toxicant is largely due to impact on the body to produce cellular toxicity. The impact of chromium and their supplementation with ascorbic acid was studied on plasma membrane of liver and kidney in male Wistar rats (80-100 g body weight). It has been observed that the intoxication with chromium (i.p.) at the dose of 0.8 mg/100 g body weight per day for a period of 28 days causes significant increase in the level of cholesterol and decrease in the level of phospholipid of both liver and kidney. The alkaline phosphatase, total ATPase and Na(+)-K(+)-ATPase activities were significantly decreased in both liver and kidney after chromium treatment, except total ATPase activity of kidney. It is suggested that chromium exposure at the present dose and duration induce for the alterations of structure and function of both liver and kidney plasma membrane. Ascorbic acid (i.p. at the dose of 0.5 mg/100 g body weight per day for period of 28 days) supplementation can reduce these structural changes in the plasma membrane of liver and kidney. But the functional changes can not be completely replenished by the ascorbic acid supplementation in response to chromium exposure. So it is also suggested that ascorbic acid (nutritional antioxidant) is useful free radical scavenger to restrain the chromium-induced membrane damage.

Comparative teratology and transplacental pharmacokinetics of all-trans-retinoic acid, 13-cis-retinoic acid, and retinyl palmitate following daily administrations in rats.

PubMed

Collins, M D; Tzimas, G; Hummler, H; Bürgin, H; Nau, H

1994-07-01

The retinoids are teratogenic in a wide variety of species. In the rat, 13-cis-retinoic acid and retinyl palmitate are significantly less potent teratogens than all-trans-retinoic acid. This investigation questioned whether differing teratogenic potencies of these moieties can be correlated with the concentrations of these drugs and/or metabolites in the embryonic compartment. Approximately equipotent teratogenic doses of these three retinoids were administered and the pharmacokinetics in maternal plasma and embryo of the most prevalent vitamin A metabolites were measured. The glucuronides of the respective retinoids were the predominant metabolites in the maternal plasma, but were not detected in the embryo. Also, the transport of 13-cis-retinoic acid across the placenta occurred to a much lesser extent than the transport of all-trans-retinoic acid. Administration of either all-trans- or 13-cis-retinoic acid causes a depression in the endogenous retinol concentration. This depression is more pronounced in the maternal plasma than in the embryo. The depression of the retinol level in both plasma and embryo after 13-cis-retinoic acid administration (75 mg/kg/day) was greater than the depression after all-trans-retinoic acid (6 mg/kg/day), corroborating the inferential teratological data that the 13-cis-retinoic acid dose was more embryotoxic than the all-trans-retinoic acid dose. Although the dose of all-trans-retinoic acid was less embryotoxic than that of either 13-cis-retinoic acid or retinyl palmitate, the embryonic exposure to all-trans-retinoic acid was considerably larger, as determined by maximum concentration or area under the concentration-versus-time curve, after administration of all-trans-retinoic acid than after either retinyl palmitate or 13-cis-retinoic acid application. These results suggest that embryonic retinoids other than all-trans-retinoic acid--including the administered substances themselves--are important in the teratogenic process induced by 13-cis-retinoic acid and retinyl palmitate.

The saturated fatty acid, palmitic acid, induces anxiety-like behavior in mice.

PubMed

Moon, Morgan L; Joesting, Jennifer J; Lawson, Marcus A; Chiu, Gabriel S; Blevins, Neil A; Kwakwa, Kristin A; Freund, Gregory G

2014-09-01

Excess fat in the diet can impact neuropsychiatric functions by negatively affecting cognition, mood and anxiety. We sought to show that the free fatty acid (FFA), palmitic acid, can cause adverse biobehaviors in mice that last beyond an acute elevation in plasma FFAs. Mice were administered palmitic acid or vehicle as a single intraperitoneal (IP) injection. Biobehaviors were profiled 2 and 24 h after palmitic acid treatment. Quantification of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their major metabolites was performed in cortex, hippocampus and amygdala. FFA concentration was determined in plasma. Relative fold change in mRNA expression of unfolded protein response (UPR)-associated genes was determined in brain regions. In a dose-dependent fashion, palmitic acid rapidly reduced mouse locomotor activity by a mechanism that did not rely on TLR4, MyD88, IL-1, IL-6 or TNFα but was dependent on fatty acid chain length. Twenty-four hours after palmitic acid administration mice exhibited anxiety-like behavior without impairment in locomotion, food intake, depressive-like behavior or spatial memory. Additionally, the serotonin metabolite 5-HIAA was increased by 33% in the amygdala 24h after palmitic acid treatment. Palmitic acid induces anxiety-like behavior in mice while increasing amygdala-based serotonin metabolism. These effects occur at a time point when plasma FFA levels are no longer elevated. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of dietary valine:lysine ratio on the performance, amino acid composition of tissues and mRNA expression of genes involved in branched-chain amino acid metabolism of weaned piglets

PubMed Central

Xu, Ye Tong; Ma, Xiao Kang; Wang, Chun Lin; Yuan, Ming Feng; Piao, Xiang Shu

2018-01-01

Objective The goal of this study was to investigate the effects of dietary standard ileal digestible (SID) valine:lysine ratios on performance, intestinal morphology, amino acids of liver and muscle, plasma indices and mRNA expression of branched-chain amino acid (BCAA) metabolism enzymes. Methods A total of 144 crossbred pigs (Duroc×Landrace×Large White) weaned at 28±4 days of age (8.79±0.02 kg body weight) were randomly allotted to 1 of 4 diets formulated to provide SID valine:lysine ratios of 50%, 60%, 70%, or 80%. Each diet was fed to 6 pens of pigs with 6 pigs per pen (3 gilts and 3 barrows) for 28 days. Results Average daily gain increased quadratically (p<0.05), the villous height of the duodenum, jejunum and ileum increased linearly (p<0.05) as the SID valine:lysine ratio increased. The concentrations of plasma α-keto isovaleric and valine increased linearly (p<0.05), plasma aspartate, asparagine and cysteine decreased (p<0.05) as the SID valine:lysine ratio increased. An increase in SID lysine:valine levels increased mRNA expression levels of mitochondrial BCAA transaminase and branched-chain α-keto acid dehydrogenase in the longissimus dorsi muscle (p<0.05). Conclusion Using a quadratic model, a SID valine:lysine ratio of 68% was shown to maximize the growth of weaned pigs which is slightly higher than the level recommended by the National Research Council [6]. PMID:28728397

Changes in plasma membrane lipids, aquaporins and proton pump of broccoli roots, as an adaptation mechanism to salinity.

PubMed

López-Pérez, Luis; Martínez-Ballesta, María Del Carmen; Maurel, Christophe; Carvajal, Micaela

2009-03-01

Salinity stress is known to modify the plasma membrane lipid and protein composition of plant cells. In this work, we determined the effects of salt stress on the lipid composition of broccoli root plasma membrane vesicles and investigated how these changes could affect water transport via aquaporins. Brassica oleracea L. var. Italica plants treated with different levels of NaCl (0, 40 or 80mM) showed significant differences in sterol and fatty acid levels. Salinity increased linoleic (18:2) and linolenic (18:3) acids and stigmasterol, but decreased palmitoleic (16:1) and oleic (18:1) acids and sitosterol. Also, the unsaturation index increased with salinity. Salinity increased the expression of aquaporins of the PIP1 and PIP2 subfamilies and the activity of the plasma membrane H(+)-ATPase. However, there was no effect of NaCl on water permeability (P(f)) values of root plasma membrane vesicles, as determined by stopped-flow light scattering. The counteracting changes in lipid composition and aquaporin expression observed in NaCl-treated plants could allow to maintain the membrane permeability to water and a higher H(+)-ATPase activity, thereby helping to reduce partially the Na(+) concentration in the cytoplasm of the cell while maintaining water uptake via cell-to-cell pathways. We propose that the modification of lipid composition could affect membrane stability and the abundance or activity of plasma membrane proteins such as aquaporins or H(+)-ATPase. This would provide a mechanism for controlling water permeability and for acclimation to salinity stress.

Plasma Triglyceride Levels May Be Modulated by Gene Expression of IQCJ, NXPH1, PHF17 and MYB in Humans.

PubMed

Vallée Marcotte, Bastien; Guénard, Frédéric; Cormier, Hubert; Lemieux, Simone; Couture, Patrick; Rudkowska, Iwona; Vohl, Marie-Claude

2017-01-26

A genome-wide association study (GWAS) by our group identified loci associated with the plasma triglyceride (TG) response to ω-3 fatty acid (FA) supplementation in IQCJ , NXPH1 , PHF17 and MYB . Our aim is to investigate potential mechanisms underlying the associations between single nucleotide polymorphisms (SNPs) in the four genes and TG levels following ω-3 FA supplementation. 208 subjects received 3 g/day of ω-3 FA (1.9-2.2 g of EPA and 1.1 g of docosahexaenoic acid (DHA)) for six weeks. Plasma TG were measured before and after the intervention. 67 SNPs were selected to increase the density of markers near GWAS hits. Genome-wide expression and methylation analyses were conducted on respectively 30 and 35 participants' blood sample together with in silico analyses. Two SNPs of IQCJ showed different affinities to splice sites depending on alleles. Expression levels were influenced by genotype for one SNP in NXPH1 and one in MYB . Associations between 12 tagged SNPs of IQCJ , 26 of NXPH1 , seven of PHF17 and four of MYB and gene-specific CpG site methylation levels were found. The response of plasma TG to ω-3 FA supplementation may be modulated by the effect of DNA methylation on expression levels of genes revealed by GWAS.

Plasma Triglyceride Levels May Be Modulated by Gene Expression of IQCJ, NXPH1, PHF17 and MYB in Humans

PubMed Central

Vallée Marcotte, Bastien; Guénard, Frédéric; Cormier, Hubert; Lemieux, Simone; Couture, Patrick; Rudkowska, Iwona; Vohl, Marie-Claude

2017-01-01

A genome-wide association study (GWAS) by our group identified loci associated with the plasma triglyceride (TG) response to ω-3 fatty acid (FA) supplementation in IQCJ, NXPH1, PHF17 and MYB. Our aim is to investigate potential mechanisms underlying the associations between single nucleotide polymorphisms (SNPs) in the four genes and TG levels following ω-3 FA supplementation. 208 subjects received 3 g/day of ω-3 FA (1.9–2.2 g of EPA and 1.1 g of docosahexaenoic acid (DHA)) for six weeks. Plasma TG were measured before and after the intervention. 67 SNPs were selected to increase the density of markers near GWAS hits. Genome-wide expression and methylation analyses were conducted on respectively 30 and 35 participants’ blood sample together with in silico analyses. Two SNPs of IQCJ showed different affinities to splice sites depending on alleles. Expression levels were influenced by genotype for one SNP in NXPH1 and one in MYB. Associations between 12 tagged SNPs of IQCJ, 26 of NXPH1, seven of PHF17 and four of MYB and gene-specific CpG site methylation levels were found. The response of plasma TG to ω-3 FA supplementation may be modulated by the effect of DNA methylation on expression levels of genes revealed by GWAS. PMID:28134766

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.

CSF/plasma ratios of amino acids: reference data and transports in children.

PubMed

Akiyama, Tomoyuki; Kobayashi, Katsuhiro; Higashikage, Akihito; Sato, Junko; Yoshinaga, Harumi

2014-01-01

We intended to investigate the effects of age, gender, and medications on amino acid cerebrospinal fluid (CSF)/plasma ratios in children, and to determine whether amino acid transports across the blood-CSF barrier in children differ from those in adults. Amino acid concentrations measured by ion-exchange high-performance liquid chromatography were used (CSF from 99 children, simultaneously collected plasma from 76 children). Influence of age, gender, and medications on the amino acid CSF concentrations and CSF/plasma ratios were analyzed by linear multiple regression. Interactions of amino acid transports were analyzed by correlation analysis of CSF/plasma ratios. CSF/plasma ratios of serine, valine, histidine, and arginine were higher in younger children. The glutamate CSF/plasma ratio was higher in older children. Serine, alanine, threonine, valine, and histidine CSF/plasma ratios were lower in females. Glutamine, methionine, tyrosine, and phenylalanine CSF/plasma ratios were elevated with valproate therapy. Serine, threonine, valine, leucine, and tyrosine CSF/plasma ratios were lower with clobazam therapy. The asparagine CSF/plasma ratio was elevated with pyridoxal phosphate therapy. Transports of most essential neutral amino acids interacted with each other, as did neutral amino acids with low molecular weights. Cationic amino acids interacted with each other and some essential neutral amino acids. Acidic amino acids had no interactions with other amino acids. Age, gender, and anti-epileptic drugs affect amino acid CSF/plasma ratios in children. Transport interactions between amino acids in children showed no remarkable difference from those of adults and generally followed the substrate specificities of multiple amino acid transport systems. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Amino acid profile and metabolic syndrome in a male Mediterranean population: A cross-sectional study.

PubMed

Ntzouvani, A; Nomikos, T; Panagiotakos, D; Fragopoulou, E; Pitsavos, C; McCann, A; Ueland, P M; Antonopoulou, S

2017-11-01

The metabolic syndrome (MetS) refers to a cluster of clinically relevant factors that increases the risk of cardiovascular diseases and all-cause mortality. Circulating levels of several amino acids and metabolites related to one-carbon metabolism have been associated with cardiometabolic risk factors and MetS. We aimed to identify the amino acid profile that is significantly associated with MetS among an all male Mediterranean population. One hundred middle-aged men (54.6 ± 8.9 years) participated in a cross-sectional study carried out during 2011-2012. The International Diabetes Federation (IDF) criteria were used to define MetS. Fasting plasma levels of 20 common amino acids and 15 metabolites related to amino acid and one-carbon metabolism were measured using gas chromatography (GC-MS/MS) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Principal components analysis was applied. Fifty-six participants fulfilled the IDF criteria for defining MetS. Five factors were extracted from the 35 measured metabolites. The branched-chain amino acids/aromatic amino acids (BCAA/AAA) related pattern and the glutamine/glycine/serine/asparagine (Gln/Gly/Ser/Asn) related pattern were significantly associated with MetS (odds ratio, 95% confidence interval; 6.41, 2.43-16.91, and 0.47, 0.23-0.96, respectively) after adjustment for age, current smoking status, physical activity level and medical treatment for hypertension, dyslipidaemia, type 2 diabetes mellitus. Further adjustment for liver function markers (i.e. glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and γ-glutamyltransferase), and plasma adiponectin levels did not significantly affect the associations. The BCAA/AAA pattern was positively associated, while the Gln/Gly/Ser/Asn pattern was inversely associated with established cardiometabolic risk factors and MetS. Plasma adiponectin levels or markers of liver function did not significantly affect these associations. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

A sensitive high-pressure liquid chromatography/particle beam/mass spectrometry assay for the determination of all-trans-retinoic acid and 13-cis-retinoic acid in human plasma.

PubMed

Lehman, P A; Franz, T J

1996-03-01

A highly sensitive assay for the measurement of all-trans-retinoic acid (tretinoin) and 13-cis-retinoic acid (isotretinoin) has been developed. Collected plasma samples were protein precipitated with 2-propanol followed by solid phase extraction. The retinoic acids were subsequently derivatized to their pentafluorobenzyl esters followed by separation and isolation by reverse phase high-pressure liquid chromatography. The HPLC eluate was directed to a mass spectrometer via a particle beam interface. Selected ion monitoring (299 m/z) for the retinoic acid's carboxylate anion produced by negative chemical ionization using methane reagent gas achieved minimum detection limits of 25 pg injected. Endogenous blood levels in 19 male and 9 female subjects were measured. It was found that females have significantly more all-trans-retinoic acid than males and that both sexes demonstrate significantly more all-trans-retinoic acid then 13-cis-retinoic acid.

Gene-diet interaction of a common FADS1 variant with marine polyunsaturated fatty acids for fatty acid composition in plasma and erythrocytes among men.

PubMed

Takkunen, Markus J; de Mello, Vanessa D; Schwab, Ursula S; Kuusisto, Johanna; Vaittinen, Maija; Ågren, Jyrki J; Laakso, Markku; Pihlajamäki, Jussi; Uusitupa, Matti I J

2016-02-01

Limited information exists on how the relationship between dietary intake of fat and fatty acids in erythrocytes and plasma is modulated by polymorphisms in the FADS gene cluster. We examined gene-diet interaction of total marine PUFA intake with a known gene encoding Δ-5 desaturase enzyme (FADS1) variant (rs174550) for fatty acids in erythrocyte membranes and plasma phospholipids (PL), cholesteryl esters (CE), and triglycerides (TG). In this cross-sectional study, fatty acid compositions were measured using GC, and total intake of polyunsaturated fat from fish and fish oil was estimated using a food frequency questionnaire in a subsample (n = 962) of the Metabolic Syndrome in Men Study. We found nominally significant gene-diet interactions for eicosapentaenoic acid (EPA, 20:5n-3) in erythrocytes (pinteraction = 0.032) and for EPA in plasma PL (pinteraction = 0.062), CE (pinteraction = 0.035), and TG (pinteraction = 0.035), as well as for docosapentaenoic acid (22:5n-3) in PL (pinteraction = 0.007). After excluding omega-3 supplement users, we found a significant gene-diet interaction for EPA in erythrocytes (pinteraction < 0.003). In a separate cohort of the Kuopio Obesity Surgery Study, the same locus was strongly associated with hepatic mRNA expression of FADS1 (p = 1.5 × 10(-10) ). FADS1 variants may modulate the relationship between marine fatty acid intake and circulating levels of long-chain omega-3 fatty acids. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Reference intervals for orotic acid in urine, plasma and dried blood spot using hydrophilic interaction liquid chromatography-tandem mass spectrometry.

PubMed

D'Apolito, Oceania; Garofalo, Daniela; la Marca, Giancarlo; Dello Russo, Antonio; Corso, Gaetano

2012-02-01

Orotic acid (OA), a marker of hereditary orotic aciduria, is usually used for the differential diagnosis of some hyperammonemic inherited defects of urea cycle and of basic amino acid transporters. This study was aimed to establish age related reference intervals of OA in urine, and for the first time in plasma, and dried blood spot (DBS) from 229 apparently healthy subjects aged from three days to 40 years. The quantification of OA was performed by a previously implemented method, using a stable isotope dilution with 1,3-[(15)N(2)]-orotic acid and hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). The method has proved to be sensitive and accurate for a quantitative analysis of OA also in DBS and plasma. According to previous studies, urinary OA levels (mmol/mol of creatinine) decrease significantly with age. The upper limits (as 99th %ile) were of 3.44 and 1.30 in groups aged from three days to 1 year (group 1) and from 1 year to 12 years (group 2), respectively; in teenagers (from 13 to 19 years; group 3) and adults (from 20 to 40 years; group 4) urinary levels became more stable and the upper limits were of 0.64 and 1.21, respectively. Furthermore, OA levels in DBS (μM) also resulted significantly higher in subjects of group 1 (upper limit of 0.89) than in subjects of groups 2, 3 and 4 (upper limits of 0.24, 0.21, and 0.29, respectively). OA levels in plasma (μM) were significantly lower in subjects of group 3 (upper limit of 0.30) than in subjects of groups 1, 2, and 4 (upper limits of 0.59, 0.48, and 0.77, respectively). This method was also employed for OA quantification in plasma and DBS of 17 newborns affected by urea cycle defects, resulting sensitive and specific enough to screen these disorders. Copyright © 2011 Elsevier B.V. All rights reserved.

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

PubMed

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

2012-03-01

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

Plasma free amino acid profiles evaluate risk of metabolic syndrome, diabetes, dyslipidemia, and hypertension in a large Asian population.

PubMed

Yamaguchi, Natsu; Mahbub, M H; Takahashi, Hidekazu; Hase, Ryosuke; Ishimaru, Yasutaka; Sunagawa, Hiroshi; Amano, Hiroki; Kobayashi-Miura, Mikiko; Kanda, Hideyuki; Fujita, Yasuyuki; Yamamoto, Hiroshi; Yamamoto, Mai; Kikuchi, Shinya; Ikeda, Atsuko; Takasu, Mariko; Kageyama, Naoko; Nakamura, Mina; Tanabe, Tsuyoshi

2017-04-07

Recently, the association of plasma free amino acid (PFAA) profile and lifestyle-related diseases has been reported. However, few studies have been reported in large Asian populations, about the usefulness of PFAAs for evaluating disease risks. We examined the ability of PFAA profiles to evaluate lifestyle-related diseases in so far the largest Asian population. We examined plasma concentrations of 19 amino acids in 8589 Japanese subjects, and determined the association with variables associated with obesity, blood glucose, lipid, and blood pressure. We also evaluated the PFAA indexes that reflect visceral fat obesity and insulin resistance. The contribution of single PFAA level and relevant PFAA indexes was also examined in the risk assessment of lifestyle-related diseases. Of the 19 amino acids, branched-chain amino acids and aromatic amino acids showed association with obesity and lipid variables. The PFAA index related to visceral fat obesity showed relatively higher correlation with variables than that of any PFAA. In the evaluation of lifestyle-related disease risks, the odds ratios of the PFAA index related to visceral fat obesity or insulin resistance with the diseases were higher than most of those of individual amino acid levels even after adjusting for potential confounding factors. The association pattern of the indexes and PFAA with each lifestyle-related disease was distinct. We confirmed the usefulness of PFAA profiles and indexes as markers for evaluating the risks of lifestyle-related diseases, including diabetes mellitus, metabolic syndrome, dyslipidemia, and hypertension in a large Asian population.

Targeted deletion of kynurenine 3-monooxygenase in mice: a new tool for studying kynurenine pathway metabolism in periphery and brain.

PubMed

Giorgini, Flaviano; Huang, Shao-Yi; Sathyasaikumar, Korrapati V; Notarangelo, Francesca M; Thomas, Marian A R; Tararina, Margarita; Wu, Hui-Qiu; Schwarcz, Robert; Muchowski, Paul J

2013-12-20

Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the kynurenine pathway (KP) of tryptophan degradation, has been suggested to play a major role in physiological and pathological events involving bioactive KP metabolites. To explore this role in greater detail, we generated mice with a targeted genetic disruption of Kmo and present here the first biochemical and neurochemical characterization of these mutant animals. Kmo(-/-) mice lacked KMO activity but showed no obvious abnormalities in the activity of four additional KP enzymes tested. As expected, Kmo(-/-) mice showed substantial reductions in the levels of its enzymatic product, 3-hydroxykynurenine, in liver, brain, and plasma. Compared with wild-type animals, the levels of the downstream metabolite quinolinic acid were also greatly decreased in liver and plasma of the mutant mice but surprisingly were only slightly reduced (by ∼20%) in the brain. The levels of three other KP metabolites: kynurenine, kynurenic acid, and anthranilic acid, were substantially, but differentially, elevated in the liver, brain, and plasma of Kmo(-/-) mice, whereas the liver and brain content of the major end product of the enzymatic cascade, NAD(+), did not differ between Kmo(-/-) and wild-type animals. When assessed by in vivo microdialysis, extracellular kynurenic acid levels were found to be significantly elevated in the brains of Kmo(-/-) mice. Taken together, these results provide further evidence that KMO plays a key regulatory role in the KP and indicate that Kmo(-/-) mice will be useful for studying tissue-specific functions of individual KP metabolites in health and disease.

Targeted Deletion of Kynurenine 3-Monooxygenase in Mice

PubMed Central

Giorgini, Flaviano; Huang, Shao-Yi; Sathyasaikumar, Korrapati V.; Notarangelo, Francesca M.; Thomas, Marian A. R.; Tararina, Margarita; Wu, Hui-Qiu; Schwarcz, Robert; Muchowski, Paul J.

2013-01-01

Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the kynurenine pathway (KP) of tryptophan degradation, has been suggested to play a major role in physiological and pathological events involving bioactive KP metabolites. To explore this role in greater detail, we generated mice with a targeted genetic disruption of Kmo and present here the first biochemical and neurochemical characterization of these mutant animals. Kmo−/− mice lacked KMO activity but showed no obvious abnormalities in the activity of four additional KP enzymes tested. As expected, Kmo−/− mice showed substantial reductions in the levels of its enzymatic product, 3-hydroxykynurenine, in liver, brain, and plasma. Compared with wild-type animals, the levels of the downstream metabolite quinolinic acid were also greatly decreased in liver and plasma of the mutant mice but surprisingly were only slightly reduced (by ∼20%) in the brain. The levels of three other KP metabolites: kynurenine, kynurenic acid, and anthranilic acid, were substantially, but differentially, elevated in the liver, brain, and plasma of Kmo−/− mice, whereas the liver and brain content of the major end product of the enzymatic cascade, NAD+, did not differ between Kmo−/− and wild-type animals. When assessed by in vivo microdialysis, extracellular kynurenic acid levels were found to be significantly elevated in the brains of Kmo−/− mice. Taken together, these results provide further evidence that KMO plays a key regulatory role in the KP and indicate that Kmo−/− mice will be useful for studying tissue-specific functions of individual KP metabolites in health and disease. PMID:24189070

Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy.

PubMed

Li, Xiaolin; Wu, Tong; Jiang, Yongjun; Zhang, Zining; Han, Xiaoxu; Geng, Wenqing; Ding, Haibo; Kang, Jing; Wang, Qi; Shang, Hong

2018-05-16

The goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. 38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). A total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. Metabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART. Copyright © 2018 Elsevier Ltd. All rights reserved.

Influence of diadenosine tetraphosphate (Ap4A) on lipid metabolism.

PubMed

Rüsing, D; Verspohl, E J

2004-01-01

Diadenosine polyphosphates (Ap(x)A) are physiologically released and may be partly involved in the pathogenesis of diabetes mellitus. Ap(4)A (diadenosine tetraphosphate) leads to an increase in blood glucose while it decreases insulin levels in plasma. A possible link between Ap(x)A and diabetes mellitus-associated diseases such as insulin resistance and hyperlipidemia (plasma free fatty acids, cholesterol and its biosynthesis, triacylglycerols) has not been investigated yet. Parameters such as free fatty acid and cholesterol content in blood were determined enzymically. The biosynthesis of cholesterol and triacylglycerols was determined in HepG2 cells using the radioactive precursor [(14)C]-acetate and by using gas chromatography. Plasma free fatty acids were significantly decreased 5 and 10 min after an Ap(4)A bolus (0.75 mg kg(-1) b.w.) given to rats. Plasma cholesterol was reduced 5 and 60 min after Ap(4)A administration. LPDS (lipoprotein-deficient serum)-stimulated cholesterol biosynthesis in HepG2 cells was significantly reduced after 1 h incubation with Ap(4)A. Triacylglycerol (TAG) biosynthesis in HepG2 cells was not significantly influenced by Ap(4)A; there was just a tendency for a concentration-dependent decrease in TAG levels. In conclusion Ap(4)A as a diabetogenetic compound is not likely to be responsible for the development of insulin resistance or of hyperlipidemia. Parameters such as free fatty acids, cholesterol and triacylglycerols are not elevated by Ap(4)A, but are even decreased. Ap(4)A seems to be involved in the development of diabetes mellitus by increasing blood glucose and decreasing plasma insulin as shown earlier, but not in diabetes mellitus-associated diseases such as insulin resistance or hyperlipidemia.

Glycoprotein changes in non-insulin dependent diabetic rats: effect of N-benzoyl-D-phenylalanine and metformin.

PubMed

Pari, Leelavinothan; Ashokkumar, Natarajan

2006-01-01

The effect of N-benzoyl-D-phenylalanine (NBDP) and metformin on neonatal streptozotocin (nSTZ) induced diabetes has been studied on plasma and tissue glycoproteins. In some pathological conditions, such as cancer, rheumatoid arthritis and diabetes, there is an abnormal glycosylation of acute phase serum proteins. As most serum proteins are produced in the liver, we have examined glycoprotein metabolism in diabetic condition. To induce non-insulin-dependent diabetes mellitus (NIDDM) a single dose of streptozotocin (100 mg/kg body weight) was injected into two day old rats. After 10-12 weeks, rats weighing above 150 g were selected for NIDDM model. In these rat, blood glucose and plasma glycoproteins were significantly increased whereas plasma insulin was significantly decreased. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in tissues. Oral administration of NBDP and metformin to diabetic rats decreased blood glucose and plasma glycoproteins. Plasma insulin and tissue sialic acid were increased whereas tissue concentrations of hexose, hexosamine and fucose were near normal. Our study suggests that NBDP and metformin possess a significant beneficial effect on glycoproteins in addition to their antidiabetic effect.

PLASMA PROTEIN PRODUCTION INFLUENCED BY AMINO ACID MIXTURES AND LACK OF ESSENTIAL AMINO ACIDS

PubMed Central

Madden, S. C.; Anderson, F. W.; Donovan, J. C.; Whipple, G. H.

1945-01-01

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and intoxication and probably to vitamin deficiency. When the diet nitrogen is provided by certain mixtures of the ten growth essential amino acids plus glycine, given intravenously at a rapid rate, plasma protein production is good. The same mixture absorbed subcutaneously at a slower rate may be slightly better utilized. Fed orally the same mixture is better utilized and associated with a lower urinary nitrogen excretion. An ample amino acid mixture for the daily intake of a 10 kilo dog may contain in grams dl-threonine 1.4, dl-valine 3, dl-leucine 3, dl-isoleucine 2, l(+)-lysine·HCl·H2O 2.2, dl-tryptophane 0.3, dl-phenylalanine 2, dl-methionine 1.2, l(+)-histidine·HCl·H2O 1, l(+)-arginine·HCl 1, and glycine 2. Half this quantity is inadequate and not improved by addition of a mixture of alanine, serine, norleucine, proline, hydroxyproline, and tyrosine totalling 1.4 gm. Aspartic acid appears to induce vomiting when added to a mixture of amino acids. The same response has been reported for glutamic acid (8). Omission from the intake of leucine or of leucine and isoleucine results in negative nitrogen balance and rapid weight loss but plasma protein production may be temporarily maintained. It is possible that leucine may be captured from red blood cell destruction. Tryptophane deficiency causes an abrupt decline in plasma protein production. No decline occurred during 2 weeks of histidine deficiency but the urinary nitrogen increased to negative balance. Plasma protein production may be impaired during conditions of dietary deficiency not related to the protein or amino acid intake. Skin lesions and liver function impairment are described. Unidentified factors present in liver and yeast appear to be involved. PMID:19871490

Effects of parenteral infusion with fish-oil or safflower-oil emulsion on hepatic lipids, plasma amino acids, and inflammatory mediators in septic rats.

PubMed

Chao, C Y; Yeh, S L; Lin, M T; Chen, W J

2000-04-01

This study was designed to investigate the effects of preinfusion with total parenteral nutrition (TPN) using fish-oil (FO) versus safflower-oil (SO) emulsion as fat sources on hepatic lipids, plasma amino-acid profiles, and inflammatory-related mediators in septic rats. Normal rats, with internal jugular catheters, were assigned to two different groups and received TPN. TPN provided 300 kcal. kg(-1). d(-1), with 40% of the non-protein energy as fat. All TPN solutions were isonitrogenous and identical in nutrient composition except for the fat emulsion, which was made of SO or FO. After receiving TPN for 6 d, each group of rats was further divided into control and sepsis subgroups. Sepsis was induced by cecal ligation and puncture; control rats received sham operation. All rats were classified into four groups as follows: FO control group (FOC; n = 7), FO sepsis group (FOS; n = 8), SO control group (SOC; n = 8), and SO sepsis group (SOS; n = 9). The results of the study demonstrated that plasma concentrations of triacylglycerol and non-esterified fatty acids did not differ between the FO and SO groups, regardless of whether the animals were septic. SOS had significantly higher total lipids and cholesterol content in the liver than did the SOC group. The FOS group, however, showed no difference from the FOC group. Plasma leucine and isoleucine levels were significantly lower in the SOS group than in the SOC group, whereas no difference in these two amino acids was observed between the FOC and FOS groups. Plasma arginine levels were significantly lower in both septic groups than in the groups without sepsis when either FO or SO was infused. Plasma glutamine levels, however, did not differ across groups. No differences in interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, or leukotriene B(4) concentrations in peritoneal lavage fluid were observed between the two septic groups. These results suggest that catabolic reaction in septic rats preinfused with FO is not as obvious as those preinfused with SO. Compared with SO emulsion, TPN with FO emulsion prevents liver fat accumulation associated with sepsis. However, parenterally administered FO had no beneficial effect in lowering cytokines and LTB(4) levels in peritoneal lavage fluid in septic rats induced by cecal ligation and puncture.

Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function

PubMed Central

Tan, Kah Ni; Carrasco-Pozo, Catalina; McDonald, Tanya S; Puchowicz, Michelle

2016-01-01

The hypothesis that chronic feeding of the triglycerides of octanoate (trioctanoin) and decanoate (tridecanoin) in “a regular non-ketogenic diet” is anticonvulsant was tested and possible mechanisms of actions were subsequently investigated. Chronic feeding of 35E% of calories from tridecanoin, but not trioctanoin, was reproducibly anticonvulsant in two acute CD1 mouse seizure models. The levels of beta-hydroxybutyrate in plasma and brain were not significantly increased by either treatment relative to control diet. The respective decanoate and octanoate levels are 76 µM and 33 µM in plasma and 1.17 and 2.88 nmol/g in brain. Tridecanoin treatment did not alter the maximal activities of several glycolytic enzymes, suggesting that there is no reduction in glycolysis contributing to anticonvulsant effects. In cultured astrocytes, 200 µM of octanoic and decanoic acids increased basal respiration and ATP turnover, suggesting that both medium chain fatty acids are used as fuel. Only decanoic acid increased mitochondrial proton leak which may reduce oxidative stress. In mitochondria isolated from hippocampal formations, tridecanoin increased respiration linked to ATP synthesis, indicating that mitochondrial metabolic functions are improved. In addition, tridecanoin increased the plasma antioxidant capacity and hippocampal mRNA levels of heme oxygenase 1, and FoxO1. PMID:27418037

Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

PubMed

Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

2017-09-01

The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

The effect of extracorporeal albumin dialysis on plasma phospholipid fatty acids in patients with end-stage liver disease.

PubMed

Zeh, Nina; Rossi, Steven S; Hofmann, Alan F; Steinbach, Joseph H; Hagey, Lee R; Oliver, Deanna; Stange, Jan; Hassanein, Tarek

2003-01-01

The effect of extracorporeal albumin dialysis (ECAD) using the MARS device on plasma phospholipid fatty acids (PLFA) in patients with end-stage liver disease (ESLD) was examined. Phospholipids were isolated from plasma and the fatty acid (FA) composition of non-sphingomyelin PL determined using capillary gas chromatography (GC). Plasma samples were also obtained from six patients with ESLD undergoing ECAD and from five patients with similar ESLD who were not treated, as well as from non-fasting healthy subjects. PLFA were much lower [506 +/- 62 microg/mL (M +/- SD)] in patients with ESLD than in healthy subjects (2709 +/- 688 microg/mL). In addition, the proportion of n3 and n6 polyunsaturated FA was much lower in patients with ESLD (n3, 1.7 +/- 0.1%, n6, 19.6 +/- 1.4%) than in healthy controls (n3, 4.1 +/- 2.4%, n6, 31.9 +/- 6.2%) ECAD caused an immediate increase in PLFA, averaging 56% in all patients, but PLFA levels decreased some hours later after treatment. ECAD also caused a small increase in the proportion of n3 and n6 of PLFA. During the 5 days of the study, PLFA rose in both ECAD-treated and untreated patients, but the increase was significantly greater in ECAD treated patient. It is concluded that patients with ESLD have markedly decreased PLFA; these PLFA have a lower proportion of the polyunsaturated n3 and n6 FA with the result that the plasma level of these essential polyunsaturated PLFA is extremely low compared to that of healthy subjects. ECAD causes a transient increase in PLFA toward normal levels and also increases the proportion of n3 and n6 FA.

Critical evaluation of lowering the recommended dietary intake of folate.

PubMed

Obeid, Rima; Koletzko, Berthold; Pietrzik, Klaus

2014-04-01

We evaluated the recommendation of the Austrian, German, and Swiss Societies for Nutrition of lowering dietary folate intake from 400 to 300 μg dietary folate equivalents/d. A dose-response relation exists between folate intake or plasma level and disease risk within the normal range. Improving folate status can prevent between 30% and 75% of neural tube defects. A prepregnancy plasma folate of >18.0 nmol/L (mean 26.1 nmol/L) is associated with low total homocysteine (tHcy) (<10.0 μmol/L) and optimal prevention of birth defects. Because the closure of the neural tube occurs in the first 8 weeks after conception, women with low prepregnancy folate intake cannot achieve maximal risk reduction. The Austrian, German, and Swiss Societies for Nutrition recommend that young women should additionally supplement with 400 μg folic acid at least 4 weeks before conception. This short time window is not sufficient to achieve optimal plasma folate and tHcy levels in the majority of women. Factors affecting the relation between folate intake and blood biomarkers are total folate intake, baseline plasma folate, time available for supplement use, dose and form (folic acid or methyl folate), genetic polymorphisms, physiological and lifestyle factors. Lowering the recommended dietary folate intake may have important public health consequences. Elderly people and young women are at risk for diseases related to folate shortage. Reducing birth defects through supplementation of folic acid remains a poor option, as <20% of young women (i.e., in Germany) supplement with the vitamin. Recommending adequate food folate intake is crucial for reaching the target protective plasma folate levels in the population. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Intestinal Fatty Acid Binding Protein as a Marker of Necrosis and Severity in Acute Pancreatitis.

PubMed

Kupčinskas, Juozas; Gedgaudas, Rolandas; Hartman, Hannes; Sippola, Tomi; Lindström, Outi; Johnson, Colin D; Regnér, Sara

2018-07-01

The aim of this study was to study intestinal fatty acid binding protein (i-FABP) as a potential biomarker in predicting severity of acute pancreatitis (AP). In a prospective multicenter cohort study, plasma levels of i-FABP were measured in 402 patients with AP. Severity of AP was determined based on the 1992 Atlanta Classification. Admission levels of plasma i-FABP were significantly higher in patients with pancreatic necrosis, in patients having systemic complications, in patients treated invasively, in patients treated in the intensive care unit, in patients with severe AP, and in deceased patients. Plasma i-FABP levels on admission yielded an area under curve (AUC) of 0.732 in discriminating patients with or without pancreatic necrosis and AUC of 0.669 in predicting severe AP. Combination of levels of i-FABP and venous lactate on the day of admission showed higher discriminative power in severe AP-AUC of 0.808. Higher i-FABP levels on admission were associated with pancreatic necrosis, systemic complications, and severe AP. Low levels of i-FABP had a high negative predictive value for pancreatic necrosis and severe AP. Combination of levels of i-FABP and venous lactates on admission were superior to either of markers used alone in predicting severe AP.

Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.

PubMed

Lemaitre, Rozenn N; Tanaka, Toshiko; Tang, Weihong; Manichaikul, Ani; Foy, Millennia; Kabagambe, Edmond K; Nettleton, Jennifer A; King, Irena B; Weng, Lu-Chen; Bhattacharya, Sayanti; Bandinelli, Stefania; Bis, Joshua C; Rich, Stephen S; Jacobs, David R; Cherubini, Antonio; McKnight, Barbara; Liang, Shuang; Gu, Xiangjun; Rice, Kenneth; Laurie, Cathy C; Lumley, Thomas; Browning, Brian L; Psaty, Bruce M; Chen, Yii-Der I; Friedlander, Yechiel; Djousse, Luc; Wu, Jason H Y; Siscovick, David S; Uitterlinden, André G; Arnett, Donna K; Ferrucci, Luigi; Fornage, Myriam; Tsai, Michael Y; Mozaffarian, Dariush; Steffen, Lyn M

2011-07-01

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

Alleviative effects of α-lipoic acid supplementation on acute heat stress-induced thermal panting and the level of plasma nonesterified fatty acids in hypothyroid broiler chickens.

PubMed

Hamano, Y

2012-01-01

1. The present study was conducted to examine the effects of α-lipoic acid on hypothyroidism-induced negative growth performance and whether α-lipoic acid alleviates acute heat stress in relation to hypothyroid status. 2. Female broiler chickens (14 d-old) were fed diets supplemented with α-lipoic acid (100 mg/kg) and an antithyroid substance, propylthiouracil (200 mg/kg), for 20 d under thermoneutral conditions (25°C). At 42 d of age, chickens were exposed to a high ambient temperature (36°C, 60% RH) for 4 h. 3. Under the thermoneutral condition, propylthiouracil administration decreased feed efficiency and concomitantly increased adipose tissue and thyroid gland weights. Plasma nonesterified fatty acids and triacylglycerol were also increased by propylthiouracil administration. However, α-lipoic acid supplementation did not affect the hypothyroidism-induced effects. 4. In hypothyroid chickens, the rise in respiratory rate induced by heat exposure was greatly inhibited by α-lipoic acid administration at 1 h, but this effect had disappeared at 4 h. In addition, a similar inhibitory effect on the concentrations of plasma nonesterified fatty acids was subsequently observed at 4 h. 5. Therefore, the present study suggested that α-lipoic acid alleviates acute heat stress if chickens are in a hypothyroid status.

Pharmacokinetic investigations in adult humans after parenteral administration of the lysine salt of acetyl-salicylic acid.

PubMed

von Voss, H; Göbel, U; Petrich, C; Pütter, J

1978-11-15

The lysine salt of acetylsalicylic acid was administered intravenously to four volunteers and intramuscularly to three of them. The drug was tolerated without any observed side effects. Immediately after intravenous application most of the plasma salicylate was acetylsalicylic acid. The highest concentration of acetylsalicylic acid was found after 2 minutes, highest levels of salicylic acid after 60 minutes. Elimination of acetylsalicylic acid was relatively quick within the first period after intravenous administration according to a half-life of 8 minutes. Half-life of salicylic acid was determined to be 3 hours. Intramuscular application results in a constant blood level for a longer period. Bioavailability of acetylsalicylic acid was slightly lower after intramuscular application than after intravenous administration.

Acute heat stress up-regulates neuropeptide Y precursor mRNA expression and alters brain and plasma concentrations of free amino acids in chicks.

PubMed

Ito, Kentaro; Bahry, Mohammad A; Hui, Yang; Furuse, Mitsuhiro; Chowdhury, Vishwajit S

2015-09-01

Heat stress causes an increase in body temperature and reduced food intake in chickens. Several neuropeptides and amino acids play a vital role in the regulation of food intake. However, the responses of neuropeptides and amino acids to heat-stress-induced food-intake regulation are poorly understood. In the current study, the hypothalamic mRNA expression of some neuropeptides related to food intake and the content of free amino acids in the brain and plasma was examined in 14-day-old chicks exposed to a high ambient temperature (HT; 40±1 °C for 2 or 5 h) or to a control thermoneutral temperature (CT; 30±1 °C). HT significantly increased rectal temperature and plasma corticosterone level and suppressed food intake. HT also increased the expression of neuropeptide Y (NPY) and agouti-signaling protein (ASIP) precursor mRNA, while no change was observed in pro-opiomelanocortin, cholecystokinin, ghrelin, or corticotropin-releasing hormone precursor mRNA. It was further found that the diencephalic content of free amino acids - namely, tryptophan, leucine, isoleucine, valine and serine - was significantly higher in HT chicks with some alterations in their plasma amino acids in comparison with CT chicks. The induction of NPY and ASIP expression and the alteration of some free amino acids during HT suggest that these changes can be the results or causes the suppression of food intake. Copyright © 2015. Published by Elsevier Inc.

Short and long-term effects of clofibric acid and diclofenac on certain biochemical and ionoregulatory responses in an Indian major carp, Cirrhinus mrigala.

PubMed

Saravanan, M; Ramesh, M

2013-09-01

Extensive use of pharmaceuticals in human and veterinary medicine and aquaculture practices pose a serious threat to aquatic organisms. In the present investigation, Cirrhinus mrigala an Indian major carp was exposed to different concentrations of clofibric acid (CA) and diclofenac (DCF) and certain biochemical and ionoregulatory responses were assessed under short and long term exposures. During short-term (96h) exposure period, plasma glucose and sodium (Na(+)) levels were increased at all concentrations (1, 10 and 100μgL(-1)) of CA and DCF treated fish. Plasma protein and chloride (Cl(-)) levels were found to be decreased at all concentrations of CA and DCF exposed fish comparatively to control groups. Meanwhile an increase in plasma potassium (K(+)) level was noted in fish exposed to CA treatments alone and in DCF treatments it was decreased. In long-term exposure (35d), plasma Na(+) and Cl(-) levels were found to be significantly increased at all concentration of CA and DCF. However, a biphasic trend was observed in plasma glucose, protein and K(+) levels. In both the treatments, a significant (P<0.01 and P<0.05) changes were observed in all parameters measured in fish exposed to different concentrations of CA and DCF. The results of the present investigation indicate that both the drugs caused significant changes in biochemical and ionoregulatory responses of fish at all concentrations. The alterations of these parameters can be useful in monitoring of pharmaceutical residues present in aquatic environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of Dietary Lipids on Endotoxemia Influences Postprandial Inflammatory Response.

PubMed

López-Moreno, Javier; García-Carpintero, Sonia; Jimenez-Lucena, Rosa; Haro, Carmen; Rangel-Zúñiga, Oriol A; Blanco-Rojo, Ruth; Yubero-Serrano, Elena M; Tinahones, Francisco J; Delgado-Lista, Javier; Pérez-Martínez, Pablo; Roche, Helen M; López-Miranda, José; Camargo, Antonio

2017-09-06

Metabolic syndrome (MetS) results in postprandial metabolic alterations that predisposes one to a state of chronic low-grade inflammation and increased oxidative stress. We aimed to assess the effect of the consumption of the quantity and quality of dietary fat on fasting and postprandial plasma lipopolysaccharides (LPS). A subgroup of 75 subjects with metabolic syndrome was randomized to receive 1 of 4 diets: HSFA, rich in saturated fat; HMUFA, rich in monounsaturated fat; LFHCC n-3, low-fat, rich in complex carbohydrate diet supplemented with n-3 polyunsaturated fatty acids; LFHCC low-fat, rich in complex carbohydrate diet supplemented with placebo, for 12 weeks each. We administered a fat challenge reflecting the fatty acid composition of the diets at postintervention. We determined the plasma lipoproteins and glucose and gene expression in peripheral blood mononuclear cells (PBMC) and adipose tissue. LPS and LPS binding protein (LBP) plasma levels were determined by ELISA, at fasting and postprandial (4 h after a fat challenge) states. We observed a postprandial increase in LPS levels after the intake of the HSFA meal, whereas we did not find any postprandial changes after the intake of the other three diets. Moreover, we found a positive relationship between the LPS plasma levels and the gene expression of IkBa and MIF1 in PBMC. No statistically significant differences in the LBP plasma levels at fasting or postprandial states were observed. Our results suggest that the consumption of HSFA diet increases the intestinal absorption of LPS which, in turn, increases postprandial endotoxemia levels and the postprandial inflammatory response.

Measurement of the total antioxidant response in preeclampsia with a novel automated method.

PubMed

Harma, Mehmet; Harma, Muge; Erel, Ozcan

2005-01-10

Preeclampsia is one of the most serious complications of pregnancy. Free radical damage has been implicated in the pathophysiology of this condition. In this study, we aimed to measure the antioxidant capacity in plasma samples from normotensive and preeclamptic pregnant women to evaluate their antioxidant status using a more recently developed automated measurement method. Our study group contained 42 women, 24 of whom had preeclampsia, while 18 had normotensive pregnancies. We measured the total plasma antioxidant capacity for all patients, as well as the levels of four major individual plasma antioxidant components; albumin, uric acid, ascorbic acid and bilirubin, and as a reciprocal measure, their total plasma peroxide levels. Statistically significant differences (determined using Student's t-test) were noted between the normotensive and the preeclamptic groups for their total antioxidant responses and their vitamin C levels (1.31 +/- 0.12 mmol versus 1.06 +/- 0.41 mmol Trolox eq./L; 30.2 +/- 17.83 micromol/L versus 18.1 +/- 11.37 micromol/L, respectively), which were both considerably reduced in the preeclamptic patients. In contrast, the total plasma peroxide levels were significantly elevated in this group (49.8 +/- 14.3 micromol/L versus 38.8 +/- 9.6 micromol/L). We found a decreased total antioxidant response in preeclamptic patients using a simple, rapid and reliable automated colorimetric assay, which may suitable for use in any routine clinical biochemistry laboratory, and considerably facilitates the assessment of this useful clinical parameter. We suggest that this novel method may be used as a routine test to evaluate and follow up of the levels of oxidative stress in preeclampsia.

Concentrations of amino acids in plasma from 45- to 47-week gestation mares and foetuses (Equus caballus).

PubMed

Zicker, S C; Vivrette, S; Rogers, Q R

1994-06-01

Concentrations of 16 of 24 amino acids in plasma of foetuses were significantly higher, while four of 24 were lower, than their concentration in maternal plasma. The higher foetal concentrations of amino acids in plasma are similar to other species, with some exceptions, and suggest that equine placenta actively transports and concentrates amino acids into the umbilical circulation. Concentrations of nine of 24 amino acids were significantly lower in plasma from the umbilical artery compared to plasma from the umbilical vein, while no significant differences were present between maternal artery and vein plasma. The umbilical venous-arterial difference in concentrations of amino acids in plasma suggests the foetus extracts amino acids from the umbilical circulation for catabolism or protein synthesis, as in other species.

Isolation and structural determination of squalene synthase inhibitor from Prunus mume fruit.

PubMed

Choi, Sung-Won; Hur, Nam-Yoon; Ahn, Soon-Cheol; Kim, Dong-Seob; Lee, Jae-Kwon; Kim, Dae-Ok; Park, Seung-Kook; Kim, Byung-Yong; Baik, Moo-Yeol

2007-12-01

Squalene synthase plays an important role in the cholesterol biosynthetic pathway. Inhibiting this enzyme in hypercholesterolemia can lower not only plasma cholesterol but also plasma triglyceride levels. A squalene synthase inhibitor was screened from Prunus mume fruit, and then purified via sequential processes of ethanol extraction, HP-20 column chromatography, ethyl acetate extraction, silica gel column chromatography, and crystallization. The squalene synthase inhibitor was identified as chlorogenic acid with a molecular mass of 354 Da and a molecular formula of C16H18O9 based on UV spectrophotometry, 1H and 13C NMRs, and mass spectrometry. Chlorogenic acid inhibited the squalene synthase of pig liver with an IC50 level of 100 nM. Since chlorogenic acid was an effective inhibitor against the squalene synthase of an animal source, it may be a potential therapeutic agent for hypercholesterolemia.

The effect of drinking water contaminated with perfluoroalkyl substances on a 10-year longitudinal trend of plasma levels in an elderly Uppsala cohort.

PubMed

Stubleski, Jordan; Salihovic, Samira; Lind, P Monica; Lind, Lars; Dunder, Linda; McCleaf, Philip; Eurén, Karin; Ahrens, Lutz; Svartengren, Magnus; van Bavel, Bert; Kärrman, Anna

2017-11-01

In 2012, drinking water contaminated with per- and polyfluoroalkyl substances (PFASs), foremost perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) at levels over 20ng/L and 40ng/L, respectively, was confirmed in Uppsala, Sweden. We assessed how a longitudinally sampled cohort's temporal trend in PFAS plasma concentration was influenced by their residential location and determined the plausible association or disparity between the PFASs detected in the drinking water and the trend in the study cohort. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort provided plasma samples three times from 2001 to 2014. Individuals maintaining the same zip code throughout the study (n = 399) were divided into a reference (no known PFAS exposure), low, intermediate and high exposure area depending on the proportion of contaminated drinking water received. Eight PFASs detected in the majority (75%) of the cohort's plasma samples were evaluated for significant changes in temporal PFAS concentrations using a random effects (mixed) model. PFHxS plasma concentrations continued to significantly increase in individuals living in areas receiving the largest percentage of contaminated drinking water (p < 0.0001), while PFOS showed an overall decrease. The temporal trend of other PFAS plasma concentrations did not show an association to the quality of drinking water received. The distribution of contaminated drinking water had a direct effect on the trend in PFHxS plasma levels among the different exposure groups, resulting in increased concentrations over time, especially in the intermediate and high exposure areas. PFOS and the remaining PFASs did not show the same relationship, suggesting other sources of exposure influenced these PFAS plasma trends. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects.

PubMed

Strajhar, P; Schmid, Y; Liakoni, E; Dolder, P C; Rentsch, K M; Kratschmar, D V; Odermatt, A; Liechti, M E

2016-03-01

Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 μg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid-chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11-dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. © 2016 British Society for Neuroendocrinology.

Rationale in diagnosis and screening of atrophic gastritis with stomach-specific plasma biomarkers

PubMed Central

Agréus, Lars; Kuipers, Ernst J; Kupcinskas, Limas; Malfertheiner, Peter; Di Mario, Francesco; Leja, Marcis; Mahachai, Varocha; Yaron, Niv; Van Oijen, Martijn; Perez, Guillermo Perez; Rugge, Massimo; Ronkainen, Jukka; Salaspuro, Mikko; Sipponen, Pentti; Sugano, Kentaro; Sung, Joseph

2012-01-01

Background and aims Atrophic gastritis (AG) results most often from Helicobacter pylori (H. pylori) infection. AG is the most important single risk condition for gastric cancer that often leads to an acid-free or hypochlorhydric stomach. In the present paper, we suggest a rationale for noninvasive screening of AG with stomach-specific biomarkers. Methods The paper summarizes a set of data on application of the biomarkers and describes how the test results could be interpreted in practice. Results In AG of the gastric corpus and fundus, the plasma levels of pepsinogen I and/or the pepsinogen I/pepsinogen II ratio are always low. The fasting level of gastrin-17 is high in AG limited to the corpus and fundus, but low or non-elevated if the AG occurs in both antrum and corpus. A low fasting level of G-17 is a sign of antral AG or indicates high intragastric acidity. Differentiation between antral AG and high intragastric acidity can be done by assaying the plasma G-17 before and after protein stimulation, or before and after administration of the proton pump inhibitors (PPI). Amidated G-17 will rise if the antral mucosa is normal in structure. H. pylori antibodies are a reliable indicator of helicobacter infection, even in patients with AG and hypochlorhydria. Conclusions Stomach-specific biomarkers provide information about the stomach health and about the function of stomach mucosa and are a noninvasive tool for diagnosis and screening of AG and acid-free stomach. PMID:22242613

Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

PubMed

Kim, Young-Je; Choi, Myung-Sook; Woo, Je Tae; Jeong, Mi Ji; Kim, Sang Ryong; Jung, Un Ju

2017-08-01

We evaluated the long-term effect of low-dose nobiletin (NOB), a polymethoxylated flavone, on diet-induced obesity and related metabolic disturbances. C57BL/6J mice were fed a high-fat diet (HFD, 45 kcal% fat) with or without NOB (0.02%, w/w) for 16 weeks. NOB did not alter food intake or body weight. Despite increases in fatty acid oxidation-related genes expression and enzymes activity in adipose tissue, NOB did not affect adipose tissue weight due to simultaneous increases in lipogenic genes expression and fatty acid synthase activity. However, NOB significantly decreased not only pro-inflammatory genes expression in adipose tissue but also proinflammatory cytokine levels in plasma. NOB-supplemented mice also showed improved glucose tolerance and insulin resistance, along with decreased levels of plasma insulin, free fatty acids, total cholesterol, non-HDL-cholesterol, and apolipoprotein B. In addition, NOB caused significant decreases in hepatic lipid droplet accumulation and triglyceride content by activating hepatic fatty acid oxidation-related enzymes. Hepatic proinflammatory TNF-α mRNA expression, collagen accumulation, and plasma levels of aminotransferases, liver damage indicators, were also significantly lower in NOB-supplemented mice. These findings suggest that long-term supplementation with low-dose NOB can protect against HFD-induced inflammation, insulin resistance, dyslipidemia, and nonalcoholic fatty liver disease, without ameliorating adiposity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neurochemical variables in schizophrenic patients during switching from neuroleptics to clozapine.

PubMed

Hatzimanolis, J; Lykouras, L; Markianos, M; Oulis, P

1998-10-01

1. The study aimed to search for the effect of clozapine on the levels of the main metabolites of dopamine homovanillic acid (HVA), serotonin 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine as well as on plasma levels of HVA, 5-HIAA, prolactin (PRL) and cortisol. 2. Seventeen male patients diagnosed as suffering from DSM-IIIR schizophrenia completed the study. 3. The patients were switched from classical antipsychotics to clozapine. After six weeks treatment with clozapine the severity of psychopathology (total BPRS score) decreased significantly (p = 0.00004). pHVA and -5-HIAA did not change significantly. uMHPG increased significantly (p = 0.017). Both PRL and cortisol levels decreased significantly (p = 0.0002, p = 0.032 respectively). Patients with high HVA levels in both plasma and urine at baseline had a lower BPRS score at the end of treatment period (p = 0.0001, p = 0.049 respectively).

Chronic administration of ellagic acid improved the cognition in middle-aged overweight men.

PubMed

Liu, Ying; Yu, Shuyi; Wang, Fen; Yu, Haitao; Li, Xueli; Dong, Wanru; Lin, Ruichao; Liu, Qingshan

2018-03-01

This study aimed to investigate if ellagic acid has beneficial effects on cognitive deficits in middle-aged overweight individuals and to propose a possible mechanism. A total of 150 middle-aged male participants, including 76 normal-weight and 74 overweight men, aged between 45 to 55 years, were recruited for this study. Both normal-weight and overweight participants were administered either 50 mg ellagic acid or placebo cellulose daily for 12 weeks. Blood lipids, peripheral brain-derived neurotrophic factor (BDNF), and saliva cortisol were assessed on the last day of the procedure to investigate the effects induced by ellagic acid. The results revealed that ellagic acid treatment improved the levels of blood lipid metabolism with a 4.7% decline in total cholesterol, 7.3% decline in triglycerides, 26.5% increase in high-density lipoprotein, and 6.5% decline in low-density lipoprotein. Additionally, ellagic acid increased plasma BDNF by 21.2% in the overweight group and showed no effects on normal-weight participants. Moreover, the increased saliva cortisol level in overweight individuals was inhibited by 22.7% in a 12-week ellagic acid treatment. Also, compared with placebo, overweight individuals who consumed ellagic acid showed enhanced cognitive function as measured by the Wechsler Adult Intelligence Scale-Revised and the Montreal Cognitive Assessment. To the best of our knowledge, this is the first report showing that ellagic acid prevents cognitive deficits through normalization of lipid metabolism, increase in plasma BDNF level, and reduction of saliva cortisol concentration. These results indicate that ellagic acid has a potential to restore cognitive performance related to mild age-related declines.

Ursolic Acid Inhibits Superoxide Production in Activated Neutrophils and Attenuates Trauma-Hemorrhage Shock-Induced Organ Injury in Rats

PubMed Central

Hwang, Tsong-Long; Shen, Hsin-I; Liu, Fu-Chao; Tsai, Hsin-I; Wu, Yang-Chang; Chang, Fang-Rong; Yu, Huang-Ping

2014-01-01

Neutrophil activation is associated with the development of organ injury after trauma–hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma–hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma–hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma–hemorrhagic shock-induced organ injury in rats. PMID:25360589

Combined n-benzoyl-d-phenylalanine and metformin treatment reverses changes in the fatty acid composition of streptozotocin diabetic rats.

PubMed

Kumar, Natarajan Ashok; Pari, Leelavinothan

2006-01-01

The present investigation was carried out to evaluate the effect of N-benzoyl-D-phenylalanine (NBDP) and metformin on blood glucose, plasma insulin, and on the fatty acid composition of total lipids in the livers and kidneys of control and experimental diabetic rats. When compared with nondiabetic control rats, neonatal streptozotocin (nSTZ) diabetic rats showed a significant increase in blood glucose and decreased plasma insulin. Analysis of fatty acids revealed a significant increase in the concentration of palmitic, stearic, and oleic acids in liver and kidney, whereas linolenic and arachidonic acids were significantly decreased. In diabetic rats, the oral administration of combined NBDP/metformin for 6 wk decreased the high concentrations of palmitic, stearic, and oleic acids and elevated the low levels of linolenic and arachidonic acids. The results suggest that the NBDP/metformin combination exhibits both antidiabetic and antihyperlipidemic effects in nSTZ diabetic rats and prevents the fatty acid changes produced during diabetes.

Amelioration of ethionine toxicity in the chick.

PubMed

Lowry, K R; Baker, D H

1987-06-01

Several chick bioassays were conducted to evaluate means of ameliorating ethionine toxicity. Supplementing a corn-soy diet marginally deficient in sulfur amino acids (methionine + cystine) with .075% D,L-ethionine reduced weight gain in 8-day-old chicks by 70% compared to gains of unsupplemented controls. Dietary addition of .50% DL-methionine prevented reduction in weight gain and feed intake resulting from ethionine supplementation whereas feeding supplemental L-cystine was without effect. Supplementation of the ethionine-containing diet with either choline or betaine ameliorated the growth depression, although neither compound was able to completely overcome the toxic effects of ethionine. Dietary ethionine did not affect plasma levels of free methionine or cystine but did increase plasma free glycine 6-fold. Dietary addition of .50% DL-methionine caused normalization of plasma glycine levels whereas it elevated plasma methionine concentration. Although results suggested the possibility of ethionine-induced serine or threonine deficiency, dietary additions of .75% L-serine or .75% L-threonine failed to improve chick weight gain. These studies suggest that ethionine, in addition to affecting transsulfuration and transmethylation activity may exert specific effects on certain amino acids in tissue pools.

Low Plasma Eicosapentaenoic Acid Levels are Associated with Elevated Trait Aggression and Impulsivity in Major Depressive Disorder with a History of Comorbid Substance Use Disorder

PubMed Central

Beier, Anne Mette; Lauritzen, Lotte; Galfalvy, Hanga C.; Cooper, Thomas B.; Oquendo, Maria A.; Grunebaum, Michael F.; Mann, J. John; Sublette, M. Elizabeth

2014-01-01

Major depressive disorder (MDD) is associated with low levels of omega-3 polyunsaturated fatty acids (PUFAs), holding promise for new perspectives on disease etiology and treatment targets. As aggressive and impulsive behaviors are associated with low omega-3 PUFA levels in some clinical contexts, we investigated plasma PUFA relationships with trait aggression and impulsivity in patients with MDD. Medication-free MDD patients (n=48) and healthy volunteers (HV, n=35) were assessed with the Brown-Goodwin Aggression Inventory. A subset (MDD, n=39; HV, n=33) completed the Barratt Impulsiveness Scale. Plasma PUFAs eicosapentaenoic acid (EPA, 20:5n-3), docosahexaenoic acid (DHA, 22:6n-3), and arachidonic acid (AA, 20:4n-6) were quantified and ln-transformed to mitigate distributional skew. Ln-transformed PUFA (lnPUFA) levels were predictors in regression models, with aggression or impulsivity scores as outcomes, and cofactors of sex and diagnostic status (MDD with or without a history of substance use disorder [SUD], or HV). Interactions were tested between relevant PUFAs and diagnostic status. Additional analyses explored possible confounds of depression severity, self-reported childhood abuse history, and, in MDD patients, suicide attempt history. Among PUFA, lnEPA but not lnDHA predicted aggression (F1,76=12.493, p=0.001), and impulsivity (F1,65=5.598, p=0.021), with interactions between lnEPA and history of SUD for both aggression (F1,76=7.941, p=0.001) and impulsivity (F1,65=3.485, p=0.037). Results remained significant when adjusted for childhood abuse, depression severity, or history of suicide attempt. In conclusion, low EPA levels were associated with aggression and impulsivity only in patients with MDD and comorbid SUD, even though in most cases SUD was in full sustained remission. PMID:25017608

Effect of obesity and metabolic syndrome on plasma oxysterols and fatty acids in human.

PubMed

Tremblay-Franco, Marie; Zerbinati, Chiara; Pacelli, Antonio; Palmaccio, Giuseppina; Lubrano, Carla; Ducheix, Simon; Guillou, Hervé; Iuliano, Luigi

2015-07-01

Obesity and the related entity metabolic syndrome are characterized by altered lipid metabolism and associated with increased morbidity risk for cardiovascular disease and cancer. Oxysterols belong to a large family of cholesterol-derived molecules known to play crucial role in many signaling pathways underlying several diseases. Little is known on the potential effect of obesity and metabolic syndrome on oxysterols in human. In this work, we questioned whether circulating oxysterols might be significantly altered in obese patients and in patients with metabolic syndrome. We also tested the potential correlation between circulating oxysterols and fatty acids. 60 obese patients and 75 patients with metabolic syndrome were enrolled in the study along with 210 age- and sex-matched healthy subjects, used as control group. Plasma oxysterols were analyzed by isotope dilution GC/MS, and plasma fatty acids profiling was assessed by gas chromatography coupled with flame ionization detection. We found considerable differences in oxysterols profiling in the two disease groups that were gender-related. Compared to controls, males showed significant differences only in 4α- and 4β-hydroxycholesterol levels in obese and metabolic syndrome patients. In contrast, females showed consistent differences in 7-oxocholesterol, 4α-hydroxycholesterol, 25-hydroxycholesterol and triol. Concerning fatty acids, we found minor differences in the levels of these variables in males of the three groups. Significant changes were observed in plasma fatty acid profile of female patients with obesity or metabolic syndrome. We found significant correlations between various oxysterols and fatty acids. In particular, 4β-hydroxycholesterol, which is reduced in obesity and metabolic syndrome, correlated with a number of saturated and mono-unsaturated fatty acids that are end-products of de novo lipogenesis. Our data provide the first evidence that obesity and metabolic syndrome are associated with major, gender-specific, changes in circulating oxysterols and fatty acids. These findings suggest a metabolic link between oxysterols and fatty acids, and that oxysterols may contribute to the epidemic diseases associated with obesity and metabolic syndrome in female. Copyright © 2015 Elsevier Inc. All rights reserved.

Echium Oil Reduces Atherosclerosis in apoB100-only LDLrKO Mice

PubMed Central

Forrest, Lolita M.; Boudyguina, Elena; Wilson, Martha D.; Parks, John S.

2012-01-01

Introduction The anti-atherogenic and hypotriglyceridemic properties of fish oil are attributed to its enrichment in eicosapentaenoic acid (EPA; 20:5, n-3) and docosahexaenoic acid (DHA; 22:6, n-3). Echium oil contains stearidonic acid (SDA; 18:4, n-3), which is metabolized to EPA in humans and mice, resulting in decreased plasma triglycerides. Objective We used apoB100 only, LDLrKO mice to investigate whether echium oil reduces atherosclerosis. Methods Mice were fed palm, echium, or fish oil-containing diets for 16 weeks and plasma lipids, lipoproteins, and atherosclerosis were measured. Results Compared to palm oil, echium oil feeding resulted in significantly less plasma triglyceride and cholesterol levels, and atherosclerosis, comparable to that of fish oil. Conclusion This is the first report that echium oil is anti-atherogenic, suggesting that it may be a botanical alternative to fish oil for atheroprotection. PMID:22100249

Metabonomics Approach to Biomarker Discovery, Volume VI: Dose and Time Response of Liver Toxicant

DTIC Science & Technology

2009-05-01

arginine, betaine, creatinine, L-threonine, L-phenylalanine, cytidylic acid , D- pyroglutamic acid , creatine, and 4-guanidinobutyric acid . However, none...Much is known about the systemic response to ANIT exposure, such as the increase in plasma levels of bile acid , cholesterol and phospholipids in...supernanant was transferred to a 5 mm NMR tube. An internal standard consisting of 150 µL of trimethylsilylpropionic (2, 2, 3, 3 d4) acid (TSP

Plasma cholesterol reduction by defatted soy ontjom (fermented with Neurospora intermedia) in rats fed a cholesterol-free diet.

PubMed

Matsuo, M

2000-02-01

To popularize defatted soy ontjom (DSB-ontjom, soy product fermented with Neurospora intermedia) as a new food, I examined the plasma cholesterol-reducing effects of DSB-ontjom and DSB in rats fed cholesterol-free diets and compared the efficiencies of these effects. DSB-ontjom greatly reduced the plasma cholesterol level and increased fecal steroid excretion as compared to DSB. DSB-ontjom was rich in pepsin-resistant protein having a high bile acid binding capacity and was abundant in isoflavone-aglycones, especially daizein. The dietary fiber (DF) of DSB-ontjom stimulated the production of short-chain fatty acids (SCFAs) by intestinal microflora. The effect of DSB-ontjom on plasma cholesterol reduction was attributed to the collaborative effects of pepsin-resistant-protein, isoflavone-aglycones and SCFA-producing DF in DSB-ontjom.

Plasma concentrations of ascorbic acid and C-reactive protein, and risk of future coronary artery disease, in apparently healthy men and women: the EPIC-Norfolk prospective population study.

PubMed

Boekholdt, S Matthijs; Meuwese, Marijn C; Day, Nicholas E; Luben, Robert; Welch, Ailsa; Wareham, Nicholas J; Khaw, Kay-Tee

2006-09-01

High plasma concentrations of ascorbic acid, a marker of fruit and vegetable intake, are associated with low risk of coronary artery disease. Whether this relationship is explained by a reduction in systemic inflammation is unclear. We investigated the relationship between ascorbic acid plasma concentration and coronary artery disease risk, and in addition whether this relationship depended on classical risk factors and C-reactive protein (CRP) concentration. We used a prospective nested case-control design. The study consisted of 979 cases and 1794 controls (1767 men and 1006 women). Increasing ascorbic acid quartiles were associated with lower age, BMI, systolic and diastolic blood pressure, and CRP concentration, but with higher HDL-cholesterol concentration. No associations existed between ascorbic acid concentration and total cholesterol concentration or LDL-cholesterol concentration. When data from men and women were pooled, the risk estimates decreased with increasing ascorbic acid quartiles such that people in the highest ascorbic acid quartile had an odds ratio for future coronary artery disease of 0.67 (95 % CI 0.52, 0.87) compared with those in the lowest quartile (P for linearity=0.001). This relationship was independent of sex, age, diabetes, smoking, BMI, LDL-cholesterol, HDL-cholesterol, systolic blood pressure and CRP level. These data suggest that the risk reduction associated with higher ascorbic acid plasma concentrations, a marker of fruit and vegetable intake, is independent of classical risk factors and also independent of CRP concentration.

Effects of saturated palmitic acid and omega-3 polyunsaturated fatty acids on Sertoli cell apoptosis.

PubMed

Hu, Xuechun; Ge, Xie; Liang, Wei; Shao, Yong; Jing, Jun; Wang, Cencen; Zeng, Rong; Yao, Bing

2018-05-25

Obesity is believed to negatively affect male semen quality and is accompanied by dysregulation of free fatty acid (FFA) metabolism in plasma. However, the implication of dysregulated FFA on semen quality and the involvement of Sertoli cells remain unclear. In the present study, we report obesity decreased Sertoli cell viability through dysregulated FFAs. We observed an increased rate of apoptosis in Sertoli cells, accompanied with elevated FFA levels, in the testes of obese mice that were provided a high-fat diet (HFD). Moreover, the levels of reactive oxygen species were elevated. Furthermore, we demonstrated by in vitro assays that saturated palmitic acid (PA), which is the most common saturated FFA in plasma, led to decreased cell viability of TM4 Sertoli cells in a time- and dose-dependent manner. A similar finding was noted in primary mouse Sertoli cells. In contrast to saturated FFA, omega-3 (ω-3) polyunsaturated fatty acids (PUFAs) protected Sertoli cells from PA-induced lipotoxicity at the physiologically relevant levels. These results indicated that the lipotoxicity of saturated fatty acids might be the cause of obesity-induced Sertoli cell apoptosis, which leads to decreased semen quality. In addition, ω-3 PUFAs could be classified as protective FFAs. FFA: free fatty acid; HFD: high-fat diet; SD: standard diet; PA: palmitic acid; PUFA: polyunsaturated fatty acid; AI: apoptotic index; MTT: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide; ROS: reactive oxygen species; HE: Hematoxylin and eosin; WT1: Wilm Tumor 1; NAFLD: non- alcoholic fatty liver disease; DCFH-DA: 2', 7' dichlorofluorescin diacetate; 36B4: acidic ribosomal phosphoprotein P0; SD: standard deviation; EPA: eicosapentaenoic acid; PI: propidium iodide; DHA: docosahexenoic acid.

Novel Genetic Loci Associated with the Plasma Triglyceride Response to an Omega-3 Fatty Acid Supplementation.

PubMed

Vallée Marcotte, Bastien; Cormier, Hubert; Guénard, Frédéric; Rudkowska, Iwona; Lemieux, Simone; Couture, Patrick; Vohl, Marie-Claude

2016-01-01

A recent genome-wide association study (GWAS) by our group identified 13 loci associated with the plasma triglyceride (TG) response to omega-3 (n-3) fatty acid (FA) supplementation. This study aimed to test whether single-nucleotide polymorphisms (SNPs) within the IQCJ, NXPH1, PHF17 and MYB genes are associated with the plasma TG response to an n-3 FA supplementation. A total of 208 subjects followed a 6-week n-3 FA supplementation of 5 g/day of fish oil (1.9-2.2 g of eicosapentaenoic acid and 1.1 g of docosahexaenoic acid). Measurements of plasma lipids were made before and after the supplementation. Sixty-seven tagged SNPs were selected to increase the density of markers near GWAS hits. In a repeated model, independent effects of the genotype and the gene-supplementation interaction were associated with plasma TG. Genotype effects were observed with two SNPs of NXPH1, and gene-diet interactions were observed with ten SNPs of IQCJ, four SNPs of NXPH1 and three SNPs of MYB. Positive and negative responders showed different genotype frequencies with nine SNPs of IQCJ, two SNPs of NXPH1 and two SNPs of MYB. Fine mapping in GWAS-associated loci allowed the identification of SNPs partly explaining the large interindividual variability observed in plasma TG levels in response to an n-3 FA supplementation. © 2016 S. Karger AG, Basel.

NMR-based metabolomic study on the toxicological effects of pesticide, diazinon on adaptation to sea water by endangered Persian sturgeon, Acipenser persicus fingerlings.

PubMed

Hajirezaee, Saeed; Mirvaghefi, Alireza; Farahmand, Hamid; Agh, Naser

2017-10-01

NMR-based metabolomics was applied to explore metabolic impacts of diazinon on sea water adaptation of Persian sturgeon fingerlings, Acipenser persicus. Fingerlings were exposed to sub-lethal concentrations of diazinon in freshwater (FW) for 96 h (short-term trial) and 12 days (long-term trial) and then exposed in brackish water (BW) (12 mg L -1 salinity) for 24 h. After 96 h and 12 days exposure in FW, identified metabolites (amino acids, osmolytes, energy metabolites) showed different change-patterns compared to control group (P < 0.05) as follow: (A) short-term trial: higher plasma levels of glucose, lactate (in all diazinon-exposed fish), acetate and acetoacetate (in 0.9 mg L -1 diazinon treatment); lower levels of creatine (in all diazinon-exposed fish), trimethylamine-N-oxide, choline, taurine, betaine, N,N-dimethylglycine and almost all amino acids in fish exposed to high concentrations of diazinon (0.54 and 0.9 mg L -1 diazinon). (B) Long-term trial: higher plasma levels of lipid oxidation metabolites and almost all amino acids in fish exposed to 0.54 and 0.9 mg L -1 diazinon; lower levels of creatine, trimethylamine-N-oxide, N,N-dimethylglycine, betaine, choline (in all diazinon-exposed fish), glucose (in 0.54 and 0.9 mg L -1 diazinon treatments) and taurine (in 0.9 mg L -1 diazinon treatment). When fish were exposed in BW for 24 h, the plasma levels of osmolytes decreased significantly in almost all experimental groups of short-term and long-term trial (P < 0.05). In short-term trial, the plasma levels of glucose in all groups and lactate in 0.18 and 0.54 mg L -1 diazinon treatments increased after salinity challenge (P < 0.05). However, a significant decrease was observed in lactate levels in 0.9 mg L -1 diazinon treatment (P < 0.05). Also, the plasma levels of amino acids decreased mostly in fish of control group than exposed fish (P < 0.05). The plasma glycerol concentration showed a significant decrease only in fish of 0.54 mg L -1 diazinon treatment (P < 0.05). In long term trial, the energetic metabolites (acetate, acetoacetate, glycerol) showed significant increases mostly in fish exposed to high concentrations of diazinon (P < 0.05). Phosphocreatine was detected only in groups exposed to 0.54 and 0.9 mg L -1 diazinon. Some amino acids decreased in control and diazinon-exposed groups while glycine (in control and 0.18 mg L -1 diazinon treatment), glutamine and alanine (in 0.9 mg L -1 diazinon treatment) elevated significantly after 24 h acclimation in BW (P < 0.05). Our results may help to understand the effects of pesticides on fish osmoregulation from a metabolic approach. Copyright © 2017. Published by Elsevier Ltd.

Plasma Protein Oxidation and Its Correlation with Antioxidant Potential During Human Aging

PubMed Central

Pandey, Kanti Bhooshan; Mehdi, Mohd Murtaza; Maurya, Pawan Kumar; Rizvi, Syed Ibrahim

2010-01-01

Previous studies have indicated that the main molecular characteristic of aging is the progressive accumulation of oxidative damages in cellular macromolecules. Proteins are one of the main molecular targets of age-related oxidative stress, which have been observed during aging process in cellular systems. Reactive oxygen species (ROS) can lead to oxidation of amino acid side chains, formation of protein-protein cross-linkages, and oxidation of the peptide backbones. In the present study, we report the age-dependent oxidative alterations in biomarkers of plasma protein oxidation: protein carbonyls (PCO), advanced oxidation protein products (AOPPs) and plasma total thiol groups (T-SH) in the Indian population and also correlate these parameters with total plasma antioxidant potential. We show an age dependent decrease in T-SH levels and increase in PCO and AOPPs level. The alterations in the levels of these parameters correlated significantly with the total antioxidant capacity of the plasma. The levels of oxidized proteins in plasma provide an excellent biomarker of oxidative stress due to the relative long half-life of such oxidized proteins. PMID:20826915

Effects of dielectric barrier discharge plasma on the inactivation of Zygosaccharomyces rouxii and quality of apple juice.

PubMed

Xiang, Qisen; Liu, Xiufang; Li, Junguang; Liu, Shengnan; Zhang, Hua; Bai, Yanhong

2018-07-15

This work aimed to evaluate the effects of dielectric barrier discharge (DBD) plasma on inactivation of spoilage yeast Zygosaccharomyces rouxii (Z. rouxii), in apple juice. Results showed that DBD plasma treatment at 90 W for 140 s resulted in about 5-log reduction of Z. rouxii in apple juice. The levels of extracellular nucleic acids and proteins as well as contents of H 2 O 2 and NO 2 - in yeast extract-peptone-dextrose (YPD) medium increased significantly after DBD plasma treatment at 90 W for 40-200 s. The increases in membrane permeability and generation of reactive species would likely contribute to DBD plasma-mediated inactivation of Z. rouxii. DBD plasma caused significant changes in pH, titratable acidity, and certain color parameters of apple juice, but had no effect on the contents of total soluble solids, reducing sugar, and total phenolics. This study provides key implications for the application of DBD plasma in fruit juice processing. Copyright © 2018 Elsevier Ltd. All rights reserved.

Spinal mechanism of micturition reflex inhibition by naftopidil in rats.

PubMed

Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki

2014-10-29

We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system. Copyright © 2014 Elsevier Inc. All rights reserved.

Arachidonic acid-containing phosphatidylcholine characterized by consolidated plasma and liver lipidomics as an early onset marker for tamoxifen-induced hepatic phospholipidosis.

PubMed

Saito, Kosuke; Goda, Keisuke; Kobayashi, Akio; Yamada, Naohito; Maekawa, Kyoko; Saito, Yoshiro; Sugai, Shoichiro

2017-08-01

Lipid profiling has emerged as an effective approach to not only screen disease and drug toxicity biomarkers but also understand their underlying mechanisms of action. Tamoxifen, a widely used antiestrogenic agent for adjuvant therapy against estrogen-positive breast cancer, possesses side effects such as hepatic steatosis and phospholipidosis (PLD). In the present study, we administered tamoxifen to Sprague-Dawley rats and used lipidomics to reveal tamoxifen-induced alteration of the hepatic lipid profile and its association with the plasma lipid profile. Treatment with tamoxifen for 28 days caused hepatic PLD in rats. We compared the plasma and liver lipid profiles in treated vs. untreated rats using a multivariate analysis to determine differences between the two groups. In total, 25 plasma and 45 liver lipids were identified and altered in the tamoxifen-treated group. Of these lipids, arachidonic acid (AA)-containing phosphatidylcholines (PCs), such as PC (17:0/20:4) and PC (18:1/20:4), were commonly reduced in both plasma and liver. Conversely, tamoxifen increased other phosphoglycerolipids in the liver, such as phosphatidylethanolamine (18:1/18:1) and phosphatidylinositol (18:0/18:2). We also examined alteration of AA-containing PCs and some phosphoglycerolipids in the pre-PLD stage and found that these lipid alterations were initiated before pathological alteration in the liver. In addition, changes in plasma and liver levels of AA-containing PCs were linearly associated. Moreover, levels of free AA and mRNA levels of AA-synthesizing enzymes, such as fatty acid desaturase 1 and 2, were decreased by tamoxifen treatment. Therefore, our study demonstrated that AA-containing PCs might have potential utility as novel and predictive biomarkers for tamoxifen-induced PLD. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Pertinent plasma indicators of the ability of chickens to synthesize and store lipids.

PubMed

Baéza, E; Jégou, M; Gondret, F; Lalande-Martin, J; Tea, I; Le Bihan-Duval, E; Berri, C; Collin, A; Métayer-Coustard, S; Louveau, I; Lagarrigue, S; Duclos, M J

2015-01-01

Excessive deposition of body fat is detrimental to production efficiency. The aim of this study was to provide plasma indicators of chickens' ability to store fat. From 3 to 9 wk of age, chickens from 2 experimental lines exhibiting a 2.5-fold difference in abdominal fat content and fed experimental diets with contrasted feed energy sources were compared. The diets contained 80 vs. 20 g of lipids and 379 vs. 514 g of starch per kg of feed, respectively, but had the same ME and total protein contents. Cellulose was used to dilute energy in the high-fat diet. At 9 wk of age, the body composition was analyzed and blood samples were collected. A metabolome-wide approach based on proton nuclear magnetic resonance spectroscopy was associated with conventional measurements of plasma parameters. A metabolomics approach showed that betaine, glutamine, and histidine were the most discriminating metabolites between groups. Betaine, uric acid, triglycerides, and phospholipids were positively correlated (r > 0.3; P < 0.05) and glutamine, histidine, triiodothyronine, homocysteine, and β-hydroxybutyrate were negatively correlated (r < -0.3; P < 0.05) with relative weight of abdominal fat and/or fat situated at the top of external face of the thigh. The combination of plasma free fatty acids, total cholesterol, phospholipid, β-hydroxybutyrate, glutamine, and methionine levels accounted for 74% of the variability of the relative weight of abdominal fat. On the other hand, the combination of plasma triglyceride and homocysteine levels accounted for 37% of the variability of fat situated at the top of external face of the thigh. The variations in plasma levels of betaine, homocysteine, uric acid, glutamine, and histidine suggest the implication of methyl donors in the control of hepatic lipid synthesis and illustrate the interplay between AA, glucose, and lipid metabolisms in growing chickens.

Advances in protein-amino acid nutrition of poultry.

PubMed

Baker, David H

2009-05-01

The ideal protein concept has allowed progress in defining requirements as well as the limiting order of amino acids in corn, soybean meal, and a corn-soybean meal mixture for growth of young chicks. Recent evidence suggests that glycine (or serine) is a key limiting amino acid in reduced protein [23% crude protein (CP) reduced to 16% CP] corn-soybean meal diets for broiler chicks. Research with sulfur amino acids has revealed that small excesses of cysteine are growth depressing in chicks fed methionine-deficient diets. Moreover, high ratios of cysteine:methionine impair utilization of the hydroxy analog of methionine, but not of methionine itself. A high level of dietary L: -cysteine (2.5% or higher) is lethal for young chicks, but a similar level of DL: -methionine, L: -cystine or N-acetyl-L: -cysteine causes no mortality. A supplemental dietary level of 3.0% L: -cysteine (7x requirement) causes acute metabolic acidosis that is characterized by a striking increase in plasma sulfate and decrease in plasma bicarbonate. S-Methylmethionine, an analog of S-adenosylmethionine, has been shown to have choline-sparing activity, but it only spares methionine when diets are deficient in choline and(or) betaine. Creatine, or its precursor guanidinoacetic acid, can spare dietary arginine in chicks.

Differential effects of mental stress on plasma homovanillic acid in schizophrenia and normal controls.

PubMed

Sumiyoshi, T; Saitoh, O; Yotsutsuji, T; Itoh, H; Kurokawa, K; Kurachi, M

1999-04-01

We previously reported that mental stress by Kraepelin's arithmetic test decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal healthy human subjects. The present study was undertaken to determine whether this pattern of changes in pHVA concentrations resulting from mental stress is altered in patients with schizophrenia. Fourteen male patients with schizophrenia including those under ongoing neuroleptic treatment and 14 normal male volunteers participated in the study. Following overnight fast and restricted physical activity, the subjects performed Kraepelin's arithmetic test for 30 minutes. Plasma samples were collected immediately before and after the test for measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect was observed due to a decrease in pHVA levels by the Kraepelin test in control subjects but not in patients with schizophrenia. Changes in pHVA levels during the Kraepelin test positively correlated with pre-test pHVA levels in control subjects, while this correlation was not observed in patients with schizophrenia. These results may be further support for the presence of a dopamine-dependent restitutive system in the brain. The absence of response of pHVA levels to mental stress in patients with schizophrenia may indicate that the dopamine restitutive system in these patients is disrupted or already down-regulated, as previously predicted.

Effect of Roux-en-Y Gastric Bypass Surgery on Bile Acid Metabolism in Normal and Obese Diabetic Rats

PubMed Central

Bhutta, Hina Y; Rajpal, Neetu; White, Wendy; Freudenberg, Johannes M.; Liu, Yaping; Way, James; Rajpal, Deepak; Cooper, David C.; Young, Andrew; Tavakkoli, Ali; Chen, Lihong

2015-01-01

In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans. PMID:25798945

Polyunsaturated fatty acids reduce insulin and very low density lipoprotein levels in broiler chickens.

PubMed

Crespo, N; Esteve-Garcia, E

2003-07-01

An experiment was conducted to study the effect of different dietary fatty acid profiles on plasma levels of insulin, very low density lipoproteins (VLDL), cholesterol, and glucose. Diets with four types of fat (tallow, olive, sunflower, and linseed oils) at an inclusion level of 10% and a basal diet without additional fat were administered to female broiler chickens. Serum insulin, cholesterol, and plasma VLDL were affected by the different treatments; however, glucose concentrations were similar among treatments. In the fasted state, broilers fed diets with sunflower or linseed oil presented lower levels of insulin and cholesterol with respect to those fed tallow or olive oil (P < 0.05). VLDL in the fasted state was reduced in broilers fed sunflower and linseed oils (P < 0.05) with respect to those fed tallow, olive oil, or the basal diet. Plasma levels of VLDL were only significantly correlated with abdominal fat in birds fed the basal diet, in the fed and in the fasted state, and in those fed linseed oil in the fed state (P < 0.05). Results of this experiment suggest that higher insulin levels in broilers fed diets rich in saturated fatty acids could be related to higher fat deposition. Fat deposition in birds fed high fat diets was not correlated with circulating VLDL, which suggested direct dietary fat deposition, except for birds fed linseed oil diets. Although birds fed linseed oil diets presented lower levels of VLDL than those fed tallow, olive oil, or the basal diet, the higher correlation with abdominal fat suggests that in these birds, fat deposition is more dependent on hepatic VLDL secretion, despite the high dietary fat level.

DNA methylation perturbations in genes involved in polyunsaturated Fatty Acid biosynthesis associated with depression and suicide risk.

PubMed

Haghighi, Fatemeh; Galfalvy, Hanga; Chen, Sean; Huang, Yung-Yu; Cooper, Thomas B; Burke, Ainsley K; Oquendo, Maria A; Mann, J John; Sublette, M Elizabeth

2015-01-01

Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59). Plasma levels of selected PUFAs along the LC-PUFA biosynthesis pathway were determined by transesterification and gas chromatography. CpG methylation levels for the main human LC-PUFA biosynthetic genes, fatty acid desaturases 1 (Fads1) and 2 (Fads2), and elongation of very long-chain fatty acids protein 5 (Elovl5), were assayed by bisulfite pyrosequencing. Associations between PUFA levels and diagnosis or suicide attempt status did not survive correction for multiple testing. However, MDD diagnosis and suicide attempts were significantly associated with DNA methylation in Elovl5 gene regulatory regions. Also the relative roles of PUFA levels and DNA methylation with respect to diagnostic and suicide attempt status were determined by least absolute shrinkage and selection operator logistic regression analyses. We found that PUFA associations with suicide attempt status were explained by effects of Elovl5 DNA methylation within the regulatory regions. The observed link between plasma PUFA levels, DNA methylation, and suicide risk may have implications for modulation of disease-associated epigenetic marks by nutritional intervention.

Bioinformatic profiling of the transcriptional response of adult rat cardiomyocytes to distinct fatty acids

USDA-ARS?s Scientific Manuscript database

Diabetes mellitus, obesity, and dyslipidemia increase risk for cardiovascular disease, and expose the heart to high plasma fatty acid (FA) levels. Recent studies suggest that distinct FA species are cardiotoxic (e.g., palmitate), while others are cardioprotective (e.g., oleate), although the molecul...

Maternal polyunsaturated fatty acid plasma levels during pregnancy and childhood adiposity. The Generation R Study

PubMed Central

Vidakovic, Aleksandra Jelena; Gishti, Olta; Voortman, Trudy; Felix, Janine F.; Williams, Michelle A.; Hofman, Albert; Demmelmair, Hans; Koletzko, Berthold; Tiemeier, Henning; Jaddoe, Vincent WV; Gaillard, Romy

2017-01-01

Background Maternal polyunsaturated fatty acid (PUFA) levels during pregnancy may have persistent effects on growth and adiposity in the offspring. Suboptimal maternal diet during pregnancy might lead to fetal cardio-metabolic adaptations with persistent consequences in the offspring. Objective We examined the associations of maternal PUFA levels during pregnancy with childhood general and abdominal fat distribution measures. Design In a population-based prospective cohort study among 4,830 mothers and their children, we measured maternal second trimester n-3 and n-6 PUFA plasma levels. At the median age of 6.0 years (95% range, 5.6–7.9), we measured childhood body mass index, fat mass percentage, android/gynoid fat ratio with dual-energy x-ray absorptiometry, and pre-peritoneal abdominal fat area with ultrasound. Analyses were adjusted for maternal and childhood socio-demographic and lifestyle related characteristics. Results We observed that higher maternal total n-3 PUFA levels, and specifically eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), docosahexaenoic acid (DHA) levels, were associated with lower childhood total body fat percentage and lower android/gynoid fat mass ratio (p-values<0.05), but not with childhood body mass index and abdominal pre-peritoneal fat mass area. Higher maternal total n-6 PUFA levels and specifically dihomo-gamma linolenic acid (DGLA) were associated with a higher childhood total body fat percentage, android/gynoid fat mass ratio and abdominal pre-peritoneal fat mass area (p-values<0.05), but not with childhood body mass index. In line with these findings, a higher maternal n-6/n-3 PUFA ratio was associated with higher childhood total body and abdominal fat mass levels. Conclusions Lower maternal n-3 PUFA levels and higher n-6 PUFA levels during pregnancy are associated with higher total body fat and abdominal fat levels in childhood. Further studies are needed to replicate these observations and to explore the causality, the underlying pathways and long-term cardio-metabolic consequences. PMID:26912493

Milk fatty acids as possible biomarkers to early diagnose elevated concentrations of blood plasma nonesterified fatty acids in dairy cows.

PubMed

Jorjong, S; van Knegsel, A T M; Verwaeren, J; Lahoz, M Val; Bruckmaier, R M; De Baets, B; Kemp, B; Fievez, V

2014-11-01

Most cows encounter a state of negative energy balance during the periparturient period, which may lead to metabolic disorders and impaired fertility. The aim of this study was to assess the potential of milk fatty acids as diagnostic tools of detrimental levels of blood plasma nonesterified fatty acids (NEFA), defined as NEFA concentrations beyond 0.6 mmol/L, in a data set of 92 early lactating cows fed a glucogenic or lipogenic diet and subjected to 0-, 30-, or 60-d dry period before parturition. Milk was collected in wk 2, 3, 4, and 8 (n = 368) and blood was sampled weekly from wk 2 to 8 after parturition. Milk was analyzed for milk fatty acids and blood plasma for NEFA. Data were classified as "at risk of detrimental blood plasma NEFA" (NEFA ≥ 0.6 mmol/L) and "not at risk of detrimental blood plasma NEFA" (NEFA <0.6 mmol/L). Concentrations of 45 milk fatty acids and milk fat C18:1 cis-9-to-C15:0 ratio were subjected to a discriminant analysis. Milk fat C18:1 cis-9 revealed the most discriminating variable to identify detrimental blood plasma NEFA. A false positive rate of 10% allowed us to diagnose 46% of the detrimental blood plasma NEFA cases based on a milk fat C18:1 cis-9 concentration of at least 230 g/kg of milk fatty acids. Additionally, it was assessed whether the milk fat C18:1 cis-9 concentrations of wk 2 could be used as an early warning for detrimental blood plasma NEFA risk during the first 8 wk in lactation. Cows with at least 240 g/kg of C18:1 cis-9 in milk fat had about 50% chance to encounter blood plasma NEFA values of 0.6 mmol/L or more during the first 8 wk of lactation, with a false positive rate of 11.4%. Profit simulations were based on costs for cows suffering from detrimental blood plasma NEFA, and costs for preventive treatment based on daily dosing of propylene glycol for 3 wk. Given the relatively low incidence rate (8% of all observations), continuous monitoring of milk fatty acids during the first 8 wk of lactation to diagnose detrimental blood plasma NEFA does not seem cost effective. On the contrary, milk fat C18:1 cis-9 of the second lactation week could be an early warning of cows at risk of detrimental blood NEFA. In this case, selective treatment may be cost effective. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Determination of glutathione in human plasma using high-performance liquid chromatography with electrochemical detection with a carbon-epoxy resin composite electrode chemically modified with cobalt phthalocyanine.

PubMed

Wring, S A; Hart, J P; Birch, B J

1989-12-01

High-performance liquid chromatography with electrochemical detection (LCEC), incorporating a novel carbon-epoxy resin working electrode modified with cobalt phthalocyanine, has been employed for preliminary studies directed towards the determination of normal circulating levels of reduced glutathione (GSH) in human plasma. The mobile phase consisted of 0.05 M phosphate buffer (pH 3) containing 0.1% m/m ethylenediaminetetraacetic acid (EDTA); the calibration graph was linear in the range 0.24-30.7 ng of GSH injected. The mean recovery of GSH added to a control serum over the physiological concentration range (0.38-3.07 ng ml-1) was 99%; this was achieved following a simple sample pre-treatment method, prior to LCEC, involving chelation of divalent cations with EDTA and subsequent acidification with orthophosphoric acid. Using the LCEC method, the mean circulating level of GSH in plasma, found in three normal subjects, was 2.69 microM, GSH; this indicates that the method might be applicable to the determination of depressed circulating levels of GSH.

Effects of running the Bostom Marathon on plasma concentrations of large neutral amino acids

NASA Technical Reports Server (NTRS)

Conlay, L. A.; Wurtman, R. J.; Lopez G-Coviella, I.; Blusztajn, J. K.; Vacanti, C. A.; Logue, M.; During, M.; Caballero, B.; Maher, T. J.; Evoniuk, G.

1989-01-01

Plasma large neutral amino acid concentrations were measured in thirty-seven subjects before and after completing the Boston Marathon. Concentrations of tyrosine, phenylalanine, and methionine increased, as did their 'plasma ratios' (i.e., the ratio of each amino acid's concentration to the summed plasma concentrations of the other large neutral amino acids which compete with it for brain uptake). No changes were noted in the plasma concentrations of tryptophan, leucine, isoleucine, nor valine; however, the 'plasma ratios' of valine, leucine, and isoleucine all decreased. These changes in plasma amino acid patterns may influence neurotransmitter synthesis.

Tetrahydro iso-alpha acids from hops improve glucose homeostasis and reduce body weight gain and metabolic endotoxemia in high-fat diet-fed mice.

PubMed

Everard, Amandine; Geurts, Lucie; Van Roye, Marie; Delzenne, Nathalie M; Cani, Patrice D

2012-01-01

Obesity and related metabolic disorders such as insulin resistance and type 2 diabetes are associated with a low-grade inflammatory state possibly through changes in gut microbiota composition and the development of higher plasma lipopolysaccharide (LPS) levels, i.e. metabolic endotoxemia. Various phytochemical compounds have been investigated as potential tools to regulate these metabolic features. Humulus lupulus L. (hops) contains several classes of compounds with anti-inflammatory potential. Recent evidence suggests that hops-derived compounds positively impact adipocyte metabolism and glucose tolerance in obese and diabetic rodents via undefined mechanisms. In this study, we found that administration of tetrahydro iso-alpha acids (termed META060) to high-fat diet (HFD)-fed obese and diabetic mice for 8 weeks reduced body weight gain, the development of fat mass, glucose intolerance, and fasted hyperinsulinemia, and normalized insulin sensitivity markers. This was associated with reduced portal plasma LPS levels, gut permeability, and higher intestinal tight junction proteins Zonula occludens-1 and occludin. Moreover, META060 treatment increased the plasma level of the anti-inflammatory cytokine interleukin-10 and decreased the plasma level of the pro-inflammatory cytokine granulocyte colony-stimulating factor. In conclusion, this research allows us to decipher a novel mechanism contributing to the positive effects of META060 treatment, and supports the need to investigate such compounds in obese and type 2 diabetic patients.

Attenuating effects of caffeic acid phenethyl ester with intralipid on hepatotoxicity of chlorpyrifos in the case of rats.

PubMed

Dokuyucu, Recep; Bilgili, Ali; Hanedan, Basak; Dogan, Hatice; Dokuyucu, Ahmet; Celik, Muhammed Murat

2016-12-22

Chlorpyrifos (CPF), insecticide widely used in agriculture, may cause poisonings in the case of humans. As a result, there is a large amount of treatment research underway to focus on the possibility of chlorpyrifos induced poisonings. The aim of this study has been to evaluate the effects of caffeic acid phenethyl ester (CAPE) and intralipid (IL) on hepatotoxicity induced by chlorpyrifos in the case of rats. The rats in this study were treated with CPF (10 mg/kg body weight (b.w.), orally), CAPE (10 μmol/kg b.w., intraperitoneally), IL (18.6 ml/kg b.w., orally), CPF+CAPE, CPF+IL, and CPF+CAPE+IL. The plasma total oxidant capacity (TOC), total antioxidant capacity (TAC) were measured and the oxidative stress index (OSI) was calculated. Liver histopathology and immunohistochemical staining were performed. Chlorpyrifos statistically significantly decreased the TAC levels in the rats' plasma and increased the apoptosis and the TOC and OSI levels. In the chlorpyrifos induced liver injury, CAPE and CAPE+IL significantly decreased the plasma OSI levels and the apoptosis, and significantly increased the plasma TAC levels. This study revealed that CAPE and CAPE+IL attenuate chlorpyrifos induced liver injuries by decreasing oxidative stress and apoptosis. Med Pr 2016;67(6):743-749. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

ELEVATED PHENYLACETIC ACID LEVELS DO NOT CORRELATE WITH ADVERSE EVENTS IN PATIENTS WITH UREA CYCLE DISORDERS OR HEPATIC ENCEPHALOPATHY AND CAN BE PREDICTED BASED ON THE PLASMA PAA TO PAGN RATIO

PubMed Central

Mokhtarani, M.; Diaz, G.A.; Rhead, W.; Berry, S.A.; Lichter-Konecki, U.; Feigenbaum, A.; Schulze, A.; Longo, N.; Bartley, J.; Berquist, W.; Gallagher, R.; Smith, W.; McCandless, S.E.; Harding, C.; Rockey, D.C.; Vierling, J.M.; Mantry, P.; Ghabril, M.; Brown, R.S.; Dickinson, K.; Moors, T.; Norris, C.; Coakley, D.; Milikien, D.A.; Nagamani, SC; LeMons, C.; Lee, B.; Scharschmidt, B.F.

2014-01-01

Background Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100), both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥500 μg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. Methods The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients ≥2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. Results Only 0.2% (11) of 4683 samples exceeded 500 ug/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio > 2.5 (both in μg/mL) in a random blood draw identified patients at risk for PAA levels > 500 μg/ml. Conclusions The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker. PMID:24144944

Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio.

PubMed

Mokhtarani, M; Diaz, G A; Rhead, W; Berry, S A; Lichter-Konecki, U; Feigenbaum, A; Schulze, A; Longo, N; Bartley, J; Berquist, W; Gallagher, R; Smith, W; McCandless, S E; Harding, C; Rockey, D C; Vierling, J M; Mantry, P; Ghabril, M; Brown, R S; Dickinson, K; Moors, T; Norris, C; Coakley, D; Milikien, D A; Nagamani, S C; Lemons, C; Lee, B; Scharschmidt, B F

2013-12-01

Phenylacetic acid (PAA) is the active moiety in sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB, HPN-100). Both are approved for treatment of urea cycle disorders (UCDs) - rare genetic disorders characterized by hyperammonemia. PAA is conjugated with glutamine in the liver to form phenylacetyleglutamine (PAGN), which is excreted in urine. PAA plasma levels ≥ 500 μg/dL have been reported to be associated with reversible neurological adverse events (AEs) in cancer patients receiving PAA intravenously. Therefore, we have investigated the relationship between PAA levels and neurological AEs in patients treated with these PAA pro-drugs as well as approaches to identifying patients most likely to experience high PAA levels. The relationship between nervous system AEs, PAA levels and the ratio of plasma PAA to PAGN were examined in 4683 blood samples taken serially from: [1] healthy adults [2], UCD patients of ≥ 2 months of age, and [3] patients with cirrhosis and hepatic encephalopathy (HE). The plasma ratio of PAA to PAGN was analyzed with respect to its utility in identifying patients at risk of high PAA values. Only 0.2% (11) of 4683 samples exceeded 500 μg/ml. There was no relationship between neurological AEs and PAA levels in UCD or HE patients, but transient AEs including headache and nausea that correlated with PAA levels were observed in healthy adults. Irrespective of population, a curvilinear relationship was observed between PAA levels and the plasma PAA:PAGN ratio, and a ratio>2.5 (both in μg/mL) in a random blood draw identified patients at risk for PAA levels>500 μg/ml. The presence of a relationship between PAA levels and reversible AEs in healthy adults but not in UCD or HE patients may reflect intrinsic differences among the populations and/or metabolic adaptation with continued dosing. The plasma PAA:PAGN ratio is a functional measure of the rate of PAA metabolism and represents a useful dosing biomarker. © 2013.

Microencapsulated krill and tuna oil blend raises plasma long-chain n-3 polyunsaturated fatty acid levels compared to tuna oil with similar increases in ileal contractility in rats.

PubMed

Patten, Glen S; Sanguansri, Luz; Augustin, Mary Ann; Abeywardena, Mahinda Y; Bird, Anthony R; Patch, Craig S; Belobrajdic, Damien P

2017-03-01

Long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) may be more bioavailable from krill oil compared to fish oil due to their phospholipid structure. We tested whether a microencapsulated krill and tuna oil blend (ME-TOKO) provided greater LC n-3 PUFA bioavailability, improved blood lipid profiles and increased intestinal contractility compared to microencapsulated tuna oil (ME-TO). Rats were divided into three groups to receive isocaloric diets containing ME-TO, ME-TOKO and microencapsulated olive oil (ME-OO) at 0.3 or 2 g/100 g for 4 weeks. Final body and organ weights, feed intake and waste output were similar. ME-TOKO rats had higher plasma total LC n-3 PUFA levels compared to ME-TO, but liver LC n-3 PUFA levels and plasma triglyceride and cholesterol levels were similar in non-fasted rats. Diets containing 2% ME-TO and ME-TOKO also showed similar increases in ileal contractility. In summary, ME-TO bioavailability of LC n-3 PUFA was similar to ME-TOKO.

Add-On Memantine Treatment for Bipolar II Disorder Comorbid with Alcohol Dependence: A 12-Week Follow-Up Study.

PubMed

Lee, Sheng-Yu; Wang, Tzu-Yun; Chen, Shiou-Lan; Chang, Yun-Hsuan; Chen, Po-See; Huang, San-Yuan; Tzeng, Nian-Sheng; Wang, Liang-Jen; Lee, I Hui; Chen, Kao Ching; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2018-06-01

Bipolar disorder (BD), especially BD-II, is frequently comorbid with alcohol dependence. Because BD-II and alcohol dependence are neurodegenerative disorders, agents with anti-inflammatory and neurotrophic effects might provide effective therapy. We investigated whether add-on memantine to regular valproic acid treatment ameliorated clinical symptoms, reduced alcohol use, and cytokine levels, and increased plasma brain-derived neurotrophic factor (BDNF) in BD-II patients with comorbid alcohol dependence. In a single-arm 12-week clinical trial, BD-II patients with comorbid alcohol dependence (n = 45) undergoing regular valproic acid treatments were given add-on memantine (5 mg/d). Symptom severity, alcohol use, cytokine (plasma tumor necrosis factor-α and C-reactive protein [CRP], transforming growth factor-β1 [TGF-β1], interleukin-8 [IL-8], IL-10), and plasma BDNF levels were regularly assessed. Mean within-group decreases in Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) scores, alcohol use, CRP, BDNF, and IL-8 levels were significantly different from baseline after 12 weeks of treatment. We found no significant correlation between alcohol use levels and changes in HDRS or YMRS scores. The correlation between reduced alcohol use and reduced TGF-β1 level was significant (B = 0.003, p = 0.019). BD-II comorbid with alcohol dependence might benefit from add-on memantine treatment, which significantly reduced clinical severity, alcohol use, and plasma cytokine levels, and increased BDNF levels. Copyright © 2018 by the Research Society on Alcoholism.

Gender difference in plasma fatty-acid-binding protein 4 levels in patients with chronic obstructive pulmonary disease

PubMed Central

Zhang, Xue; Li, Diandian; Wang, Hao; Pang, Caishuang; Wu, Yanqiu; Wen, Fuqiang

2016-01-01

COPD (chronic obstructive pulmonary disease) is characterized by airway inflammation and increases the likelihood of the development of atherosclerosis. Recent studies have indicated that FABP4 (fatty-acid-binding protein 4), an intracellular lipid chaperone of low molecular mass, plays an important role in the regulation of inflammation and atherosclerosis. We carried out a preliminary clinical study aiming at investigating the relationships between circulating FABP4 levels in patients with COPD and inflammation and lung function. We enrolled 50 COPD patients and 39 healthy controls in the study. Lung function tests were performed in all subjects. Plasma levels of FABP4 and adiponectin, TNFα (tumour necrosis factor α) and CRP (C-reactive protein) were measured. The correlations between FABP4 and lung function, adipokine (adiponectin), inflammatory factors and BMI (body mass index) were analysed. Compared with both males with COPD and healthy females, plasma FABP4 levels in females with COPD were significantly increased. Adiponectin and CRP levels were significantly higher in patients with COPD. Furthermore, we found that FABP4 levels were inversely correlated with FEV1% predicted (FEV1 is forced expiratory volume in 1 s) and positively correlated with adiponectin and TNFα in COPD patients. In addition, a positive correlation between plasma FABP4 and CRP was found in females with COPD. However, FABP4 levels were not correlated with BMI. Our results underline a gender difference in FABP4 secretion in stable COPD patients. Further studies are warranted to clarify the exact role of FABP4 in the pathogenesis of COPD. PMID:26823558

Effect of ursodeoxycholic acid on bile acid profiles and intestinal detoxification machinery in primary biliary cirrhosis and health.

PubMed

Dilger, Karin; Hohenester, Simon; Winkler-Budenhofer, Ursula; Bastiaansen, Barbara A J; Schaap, Frank G; Rust, Christian; Beuers, Ulrich

2012-07-01

Ursodeoxycholic acid (UDCA) exerts anticholestatic, antifibrotic and antiproliferative effects in primary biliary cirrhosis (PBC) via mechanisms not yet fully understood. Its adequate biliary enrichment is considered mandatory for therapeutic efficacy. However, precise determination of biliary enrichment of UDCA is not possible in clinical practice. Therefore, we investigated (i) the relationship between biliary enrichment and plasma pharmacokinetics of UDCA, (ii) the effect of UDCA on plasma and biliary bile acid composition and conjugation patterns, and (iii) on the intestinal detoxification machinery in patients with PBC and healthy controls. In 11 PBC patients and 11 matched healthy subjects, cystic bile and duodenal tissue were collected before and after 3 weeks of administration of UDCA (15 mg/kg/day). Extensive pharmacokinetic profiling of bile acids was performed. The effect of UDCA on the intestinal detoxification machinery was studied by quantitative PCR and Western blotting. The relative fraction of UDCA and its conjugates in plasma at trough level[x] correlated with their biliary enrichment[y] (r=0.73, p=0.0001, y=3.65+0.49x). Taurine conjugates of the major hydrophobic bile acid, chenodeoxycholic acid, were more prominent in bile of PBC patients than in that of healthy controls. Biliary bile acid conjugation patterns normalized after treatment with UDCA. UDCA induced duodenal expression of key export pumps, BCRP and P-glycoprotein. Biliary and trough plasma enrichment of UDCA are closely correlated in PBC and health. Taurine conjugation may represent an adaptive mechanism in PBC against chenodeoxycholic acid-mediated bile duct damage. UDCA may stabilize small intestinal detoxification by upregulation of efflux pumps. Copyright © 2012. Published by Elsevier B.V.

Lipid Lowering Effect of Antioxidant Alpha-Lipoic Acid in Experimental Atherosclerosis

PubMed Central

Amom, Zulkhairi; Zakaria, Zaiton; Mohamed, Jamaluddin; Azlan, Azrina; Bahari, Hasnah; Taufik Hidayat Baharuldin, Mohd; Aris Moklas, Mohd; Osman, Khairul; Asmawi, Zanariyah; Kamal Nik Hassan, Mohd

2008-01-01

Accumulating data demonstrated that hypercholesterolemia and oxidative stress play an important role in the development of atherosclerosis. In the present study, a protective activity of alpha-lipoic acid; a metabolic antioxidant in hypercholesterolemic-induced animals was investigated. Eighteen adult male New Zealand White (NZW) rabbit were segregated into three groups labelled as group N, HCD and ALA (n = 6). Group N (normal control) was fed with normal chow, the rest (HCD and ALA) were fed with 100 g/head/day of 1% cholesterol rich diet to induce hypercholesterolemia. Four point two mg/body weight of alpha lipoic acid was concomintantly supplemented to the ALA group. Drinking water was given ad-libitum. The study was designed for 10 weeks. Blood sampling was taken from the ear lobe vein at the beginning, week 5 and week 10. Plasma was prepared for lipid profile estimation and microsomal lipid peroxidation index indicated with malondialdehyde (MDA) formation. At the end of the experiment, the animals were sacrificed and the aorta were excised for intimal lesion analysis. The plasma total cholesterol (TC) and low density lipoprotein (LDL) levels were found to be significantly low in ALA group compared to that of the HCD group (p<0.05). Similarly, low level of MDA (p<0.05) in ALA group was observed compared to that of the HCD group showing a significant reduction of lipid peroxidation activity. Histomorphometric intimal lesion analysis of the aorta showing less of atheromatous plaque formation in alpha lipoic acid supplemented group (p<0.05) compared to HCD group. These findings suggested that alpha lipoic acid posses a dual lipid lowering and anti-atherosclerotic properties indicated with low plasma TC and LDL levels and reduction of athero-lesion formation in hypercholesterolemic-induced rabbits. PMID:18818758

FABP4 inhibitor BMS309403 decreases saturated-fatty-acid-induced endoplasmic reticulum stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation.

PubMed

Bosquet, Alba; Girona, Josefa; Guaita-Esteruelas, Sandra; Heras, Mercedes; Saavedra-García, Paula; Martínez-Micaelo, Neus; Masana, Lluís; Rodríguez-Calvo, Ricardo

2018-06-01

Fatty acid binding protein 4 (FABP4) inhibitors have been proposed as potential therapeutic approaches against insulin resistance-related inflammation and type 2 diabetes mellitus. However, the underlying molecular mechanisms by which these molecules drive these effects in skeletal muscle remain unknown. Here, we assessed whether the FABP4 inhibitor BMS309403 prevented lipid-induced endoplasmic reticulum (ER) stress-associated inflammation in skeletal muscle. The BMS309403 treatment was assessed both in the skeletal muscle of high-fat diet (HFD)-fed mice and in palmitate-stimulated C2C12 myotubes. HFD feeding promoted insulin resistance, which is characterized by increased plasma levels of glucose, insulin, non-esterified fatty acids, triglycerides, resistin, and leptin and reduced plasma levels of adiponectin compared with control mice fed a standard diet. Additionally, insulin-resistant animals showed increased FABP4 plasma levels. In line with this evidence, recombinant FABP4 attenuated the insulin-induced AKT phosphorylation in C2C12 myotubes. Treatment with BMS309403 reduced lipid-induced ER stress and inflammation in both mouse skeletal muscle and C2C12 myotubes. The effects of the FABP4 inhibitor reducing lipid-induced ER stress-associated inflammation were related to the reduction of fatty acid-induced intramyocellular lipid deposits, ROS and nuclear factor-kappaB (NF-κB) nuclear translocation. Accordingly, BMS309403 reduced lipid-induced p38 MAPK phosphorylation, which is upstream of NF-κB activation. Overall, these findings indicate that BMS309403 reduces fatty acid-induced ER stress-associated inflammation in skeletal muscle by reducing p38 MAPK activation. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of branched-chain amino acid composition of culture media on the synthesis of plasma proteins by serum-free cultured rat hepatocytes.

PubMed

Montoya, A; Gómez-Lechón, M J; Castell, J V

1989-04-01

Supplementation of Ham's F12 culture medium with essential amino acids (EAA) up to the rat plasma levels increased the rates of synthesis of albumin and transferrin by cultured rat hepatocytes by 1.3 and 1.7, respectively. Fifty percent of this increase could be attributed to three of the EAA: the branched-chain amino acids (BCAA: Leu Ile and Val). Non-branched-chain essential amino acids (non-BC-EAA) stimulated only 25% of the increase produced by the whole EAA mixture. When each EAA was tested individually, none of them caused an appreciable increase in albumin and transferrin in culture medium. When the concentrations of all EAA were raised to rat postprandial portal levels, albumin and transferrin synthesis rates reached a maximum, increasing by 3.2 and 3.5, respectively. Supplementation with BCAA at postprandial portal concentrations increased albumin and transferrin synthesis rates by 2.2 and 2.0, respectively, and had no noteworthy effect on the synthesis of cellular proteins. Non-BC-EAA at their postprandial portal concentrations increased albumin and transferrin synthesis rates by 1.7 and 1.9, respectively. Supplementation with alanine to reach a nitrogen content equal to that of the modified EAA-enriched medium had no stimulatory effect. Our results show that EAA have a specific effect on the synthesis of plasma proteins by cultured hepatocytes, and that BCAA at physiologic concentrations account for the major part of this stimulatory effect. Consequently, EAA and particularly BCAA concentration should be elevated in serum-free nutrient media to sustain maximum plasma protein synthesis.

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.

Relationship between plasma adropin levels and body composition and lipid characteristics amongst young adolescents in Taiwan.

PubMed

Chang, Jin-Biou; Chu, Nain-Feng; Lin, Fu-Huang; Hsu, Jhu-Ting; Chen, Pi-Yun

Adropin is a 76 amino acid peptide hormone with a molecular weight of 4999.9Da that may be associated with energy homeostasis, insulin resistance and lipid metabolism in mice and human. There is only a few studies that examine plasma adropin levels and body composition in children. This study is to evaluate the relationship between plasma adropin levels, body composition and lipid variables amongst young adolescents in Taiwan. We examined 492 adolescents (269 females and 223 males) ranging from 12 to 15 years old, with a mean age of 13.6 years. Body composition was measured using impedance method by Tanita-BC418. Plasma lipid variables were measured using standard methods and plasma adropin levels were measured using the ELISA method. There was no significant difference in plasma adropin levels between males and females (3.52 vs. 3.58ng/ml). Plasma adropin levels were negatively correlated with fat free mass (r=-0.12, p<0.01). More interestingly, children with higher plasma adropin levels had lower waist-to-hip ratios (WHR) and lower body fat percentage by mass. Furthermore, there is no difference in lipid profiles in high vs. low adropin subjects. Plasma adropin levels are not consistency associated with body composition and no association with lipid variables amongst Taiwanese adolescents. The role of adropin in the development of obesity is still not clear, and further studies are need especially for children. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Regulation of blood glucose level by kainic acid in mice: involvement of glucocorticoid system and non-NMDA receptors.

PubMed

Kim, Chea-Ha; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Sung-Su; Jung, Jun-Sub; Sharma, Naveen; Suh, Hong-Won

2017-02-28

Kainic acid (KA) is a well-known excitatory neurotoxic substance. In the present study, effects of KA-injected intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level were investigated in ICR mice. We found that KA administered intraperitoneally (i.p.), intracerebroventricularly (i.c.v.) or intrathecally (i.t.) increased the blood glucose and corticosterone levels, suggesting that KA-induced hyperglycemia appeared to be due to increased blood corticosterone level. In support of this finding, adrenalectomy causes a reduction of KA-induced hyperglycemia and neuronal cell death in CA3 regions of the hippocampus. In addition, pretreatment with i.c.v. or i.t. injection of CNQX (6-cyano-7-nitroquinoxaline-2, 3-dione; a non-NMDA receptor blocker) attenuated the i.p. and i.c.v. administered KA-induced hyperglycemia. KA administered i.c.v. caused an elevation of the blood corticosterone level whereas the plasma insulin level was reduced. Moreover, i.c.v. pretreatment with CNQX inhibited the decrease of plasma insulin level induced by KA i.c.v. injection, whereas the KA-induced plasma corticosterone level was further enhanced by CNQX pretreatment. Our results suggest that KA administered systemically or centrally produces hyperglycemia. A glucocorticoid system appears to be involved in KA-induced hyperglycemia. Furthermore, central non-N-methyl-D-aspartate receptors may be responsible for KA-induced hyperglycemia.

Common FABP4 genetic variants and plasma levels of fatty acid binding protein 4 in older adults.

PubMed

Mukamal, Kenneth J; Wilk, Jemma B; Biggs, Mary L; Jensen, Majken K; Ix, Joachim H; Kizer, Jorge R; Tracy, Russell P; Zieman, Susan J; Mozaffarian, Dariush; Psaty, Bruce M; Siscovick, David S; Djoussé, Luc

2013-11-01

We examined common variants in the fatty acid binding protein 4 gene (FABP4) and plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409, rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190 European Americans and 660 African Americans. Among European Americans, the minor alleles of six single nucleotide polymorphisms (SNP) were associated with lower FABP4 levels (all p ≤ 0.01). Among African Americans, the SNP with the lowest minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C-A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in both European Americans (frequency = 16 %; p = 0.001) and African Americans (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron with one in the 3'untranslated region. However, the alleles associated with lower FABP4 levels were associated with higher fasting glucose in meta-analyses from the MAGIC consortium. These results demonstrate associations of common SNP and haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose levels.

[Catecholamines and their metabolites in children with Asperger and Kanner syndromes].

PubMed

Gorina, A S; Kolesnichenko, L S; Mikhnovich, V I

2011-01-01

Children with Asperger and Kanner syndromes in the stable state demonstrate similar decrease in plasma norepinephrine. In the aggravated state, these changes become more expressed and are characterized by a decrease in plasma tyrosine, norepinephrine, normetanephrine and by an increase in dopamine and homovanylic acid and a decrease in excretion of norepinephrine and an increase in excretion of homovanylic acid, epinephrine and MHPG. Only in children with Kanner syndrome in the aggravated state plasma MHPG increases, excretion of tyrosine decreases and excretion of normetanephrine increases. The observed imbalance in dopamine and epinephrine/norepinephrine systems justifies combined analysis of changes in catecholamines and their metabolites levels as the most informative approach in the study of the effect of autistic disorders.

The effects of diet and physical activity on plasma homovanillic acid in normal human subjects.

PubMed

Kendler, K S; Mohs, R C; Davis, K L

1983-03-01

This study examines the effect of diet and moderate physical activity on plasma levels of the dopamine metabolite homovanillic acid (HVA) in healthy young males. At weekly intervals, subjects were fed four isocaloric meals: polycose (pure carbohydrate), sustecal, low monoamine, and high monoamine. Moderate physical activity consisted of 30 minutes of exercise on a bicycle ergometer. The effect of diet on plasma HVA (pHVA) was highly significant. Compared to the polycose meal, the high monoamine meal significantly increased pHVA. Moderate physical activity also significantly increased pHVA. Future clinical studies using pHVA in man as an index of brain dopamine function should control for the effects of both diet and physical activity.

Nitric oxide and oxidative stress is associated with severity of diabetic retinopathy and retinal structural alterations.

PubMed

Sharma, Shashi; Saxena, Sandeep; Srivastav, Khushboo; Shukla, Rajendra K; Mishra, Nibha; Meyer, Carsten H; Kruzliak, Peter; Khanna, Vinay K

2015-07-01

The aim of the study was to determine plasma nitric oxide (NO) and lipid peroxide (LPO) levels in diabetic retinopathy and its association with severity of disease. Prospective observational study. A total of 60 consecutive cases and 20 healthy controls were included. Severity of retinopathy was graded according to early treatment diabetic retinopathy study (ETDRS) classification. Photoreceptor inner segment ellipsoid band (ISel) disruption and retinal pigment epithelium (RPE) alteration were graded using spectral domain optical coherence tomography. Data were statistically analyzed. Plasma thiobarbituric acid reactive substances, NO assay and reduced glutathione (GSH) were measured using standard protocol. Increased severity of diabetic retinopathy was significantly associated with increase in plasma levels of LPO (P < 0.05), NO (P < 0.001) and decrease in plasma levels of GSH (P < 0.0001), ISel disruption (P < 0.001) and RPE topographic alteration (P < 0.01). Increased plasma NO levels are associated with increased severity of diabetic retinopathy. For the first time, it has been demonstrated that increased plasma LPO, NO and decreased GSH levels are associated with in vivo structural changes in inner segment ellipsoid and RPE. © 2015 Royal Australian and New Zealand College of Ophthalmologists.