Plasma Lipid Concentrations Research Articles

The rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene is associated with obesity in Tunisian population

Context: Variations in the fat mass and obesity-associated gene (FTO) has been associated with obesity in many populations, but the results are conflicting.Objective: The aim of this study was to evaluate the effect of the rs9939609 polymorphism in the FTO gene on obesity risk and plasma leptin, adiponectin, insulin and lipid concentrations in Tunisians.Materials and methods: Four hundred and ninety-four subjects with obesity and 334 non-obese participated in this study. The rs9939609 (T/A) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.Results: Significant differences in genotype frequencies were observed between cases and controls. In the separate analysis by gender, the association between the AA genotype and obesity was statistically significant in women but not in men. After stratification by obesity class this association remains only with obesity class III.Discussion: Our study is in agreement with studies on Caucasian, Portuguese and Cebu Filipino populations where a gender-specific association was found between rs9939609 polymorphism and obesity. It is also in agreement with studies on Mexican, Spanish and European populations, where an association was found with obesity class III.Conclusion: The rs9939609 polymorphism of FTO gene is associated with obesity, especially obesity class III in women.

Obstructive sleep apnoea independently predicts lipid levels: Data from the European Sleep Apnea Database.

Obstructive sleep apnoea (OSA) and dyslipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and plasma lipid concentrations in patients enrolled in the European Sleep Apnea Database (ESADA) cohort. The cross-sectional analysis included 8592 patients without physician-diagnosed hyperlipidaemia or reported intake of a lipid-lowering drug (age 50.1 ± 12.7 years, 69.1% male, BMI: 30.8 ± 6.6 kg/m2 , mean apnoea-hypopnoea index (AHI): 25.7 ± 25.9 events/h). The independent relationship between measures of OSA (AHI, oxygen desaturation index (ODI), mean and lowest oxygen saturation) and lipid profile (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and fasting triglycerides (TG)) was determined by means of general linear model analysis. There was a dose response relationship between TC and ODI (mean ± SE (mg/dL): 180.33 ± 2.46, 184.59 ± 2.42, 185.44 ± 2.42 and 185.73 ± 2.44; P < 0.001 across ODI quartiles I-IV). TG and LDL concentrations were better predicted by AHI than by ODI. HDL-C was significantly reduced in the highest AHI quartile (mean ± SE (mg/dL): 48.8 ± 1.49 vs 46.50 ± 1.48; P = 0.002, AHI quartile I vs IV). Morbid obesity was associated with lower TC and higher HDL-C values. Lipid status was influenced by geographical location with the highest TC concentration recorded in Northern Europe. OSA severity was independently associated with cholesterol and TG concentrations.

Alcohol consumption and probable rapid eye movement sleep behavior disorder.

ObjectiveTo systematically examine the association between alcohol intake and likelihood of having probable rapid eye movement sleep behavior disorder (pRBD) 6 years later.MethodsThe study included 11,905 participants (mean age: 47.7 years) of the Kailuan Study, free of stroke, cancer, Parkinson disease, dementia, and head injury in 2006. We determined pRBD using a validated RBD questionnaire–Hong Kong in 2012. Amounts and types of alcohol intake were collected with questionnaire. Participants were categorized into: nondrinkers, light (women: 0–0.4 servings/day; men: 0–0.9 servings/day), moderate (women: 0.5–1.0 servings/day; men: 1–2 servings/day), and heavy drinkers(women: >1 serving/day; men: >2 servings/day). To examine the alcohol‐pRBD relationship, we used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for demographic characteristics, smoking, hypertension, diabetes, physical activity, body mass index, and plasma concentrations of lipids and urate.ResultsCompared with nondrinkers, current drinkers had a 23% higher likelihood of having pRBD (adjusted OR 1.23, 95% CI 1.07–1.59). Both moderate (adjusted OR: 1.53, 95% CI 1.01–2.30) and heavy drinkers (adjusted OR: 1.29, 95% CI 1.00–1.66), but not light drinkers (adjusted OR: 1.16, 95% CI 0.94–1.44), had a significantly higher likelihood of having pRBD, relative to nondrinkers. There was a nonsignificant trend between consumption of each individual alcoholic beverages (i.e., beer, wine, or hard liquor) and higher likelihood of having pRBD (adjusted ORs ranged from 1.11 to 1.49).ConclusionsAlcohol consumption was associated with a higher likelihood of having pRBD. Future prospective studies with clinically confirmed RBD, large sample size for information on types of alcoholic beverage are warranted.

Cumin (Cuminum cyminum L.) is a safe approach for management of lipid parameters: A systematic review and meta-analysis of randomized controlled trials.

We performed a meta-analysis to evaluate the efficacy of cumin supplementation on plasma lipid concentration in adult population. The search included PubMed, Scopus, ISI Web of Science, Google Scholar, and the Cochrane library (up to January 2018) to identify randomized controlled trials (RCTs) investigating the effects of cumin supplementation on serum lipid parameters. Mean difference (MD) was pooled using a random-effects model. Meta-analysis of data from six eligible RCTs with 376 participants showed a significant reduction in plasma concentration of total cholesterol (MD [95% CI] -10.90 [-21.39, -0.42] mg/dl, p=0.042) and low-density lipoprotein cholesterol (MD [95% CI] -6.94 [-11.53, -2.35] mg/dl, p=0.003) after supplementation with cumin compared with control treatment, and plasma concentration of high-density lipoprotein cholesterol (MD [95% CI] 3.35 [1.58, 5.12] mg/dl, p˂0.001) were found to be increased. Although our analysis indicated that cumin supplementation cannot change triglyceride (TG) concentration (MD [95% CI] -20.48 [-41.23, -0.26] mg/dl, p=0.053), but after stratified the RCTs based on the primary level of TG (hypertriglyceridemia versus nonhypertriglyceridemia subjects), there was a significant decrease in nonhypertriglyceridemia subset. This systematic review and meta-analysis suggested the efficacy of cumin supplementation on lipid parameters.

A preliminary study of the association between the ABCA1 gene promoter DNA methylation and coronary artery disease risk.

Coronary artery disease (CAD) is a common health problem in Iranian population. ATP binding cassette transporter A1 (ABCA1) plays central role in the efflux of the cholesterol from peripheral tissues back to liver. Inactivation of ABCA1 by epigenetic change such as DNA methylation may contribute to the development of CAD. The present study investigated the association between promoter DNA methylation status of ABCA1 with the development and severity of CAD. Our study population consisted of 110 angiographically documented CAD patients and 110 controls. The severity of CAD was determined based on the number of stenotic vessels showing more than 50% stenosis. Promoter DNA methylation status of ABCA1 was determined by methylation specific PCR. Lipid profile was determined by routine colorimetric methods. Results showed that the frequency of ABCA1 DNA methylation was significantly higher in CAD group as compared with control group (16.36% vs 5.45%; P=0.015). Also, the methylation frequency of ABCA1 gene was significantly higher in older CAD patients as compared with younger CAD patients (P=0.038). No association was seen between plasma lipid concentration and the promoter DNA methylation status of ABCA1 (P>0.05). Also, the association between the severity of CAD and methylation of ABCA1 gene was not significant (P>0.05). In conclusion the current study indicated ABCA1 DNA methylation as a significant risk factor for development but not severity of CAD. Also, predisposition to the development of CAD by ABCA1 gene DNA methylation was independent of plasma lipid concentration.

YangXue QingNao Wan and Silibinin Capsules, the Two Chinese Medicines, Attenuate Cognitive Impairment in Aged LDLR (+/-) Golden Syrian Hamsters Involving Protection of Blood Brain Barrier.

The purpose of the study was to explore the effect and the underlying mechanism of YangXue QingNao Wan (YXQNW) and Silibinin Capsules (SC), the two Chinese medicines, on cognitive impairment in older people with familial hyperlipidaemia. Fourteen month-old female LDLR (+/-) golden Syrian hamsters were used with their wild type as control. YXQNW (0.5 g/kg/day), SC (0.1 g/kg/day), or YXQNW (0.5 g/kg/day) + SC (0.1 g/kg/day) were administrated orally for 30 days. To assess the effects of the two drugs on plasma lipid content and cognitive ability, plasma TC, TG, LDL-C, and HDL-C were measured, and Y maze task was carried out both before and after administration. After administering of the drugs for 30 days, to evaluate the effect of the two drugs on disturbed blood flow caused by hyperlipidemia, the cerebral blood flow (CBF) was measured. To assess blood–brain barrier integrity, albumin leakage in middle cerebral artery (MCA) area was determined. To evaluate the effect of the drugs on impaired microvessels, the number and morphology of microvessels were assessed in hippocampus area. To further evaluate the ultrastructure of microvessels in hippocampus, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were carried out. To assess the profiles of claudin-5 and occludin in hippocampus, we performed immunofluorescence. Finally, to assess the expression of claudin-5, JAM-1, occludin and ZO-1 in hippocampus, western blot was carried out. The results showed that YXQNW, SC, and YXQNW + SC improved cognitive impairment of aged LDLR (+/-) golden Syrian hamsters without lowering plasma TC and LDL-C. YXQNW, SC, and YXQNW + SC attenuated albumin leakage in MCA area and neuronal damage in hippocampus, concomitant with an increase in CBF, a decrease of perivascular edema and an up-regulated expression of claudin-5, occludin and ZO-1. In conclusion, YXQNW, SC, and YXQNW + SC are able to improve cognitive ability in aged LDLR (+/-) golden Syrian hamsters via mechanisms involving maintaining blood–brain barrier integrity. These findings provide evidence suggesting YXQNW or SC as a potential regime to counteract the cognitive impairment caused by familial hypercholesterolemia.

Central adiposity markers, plasma lipid profile and cardiometabolic risk prediction in overweight-obese individuals

Waist circumference (WC) is the currently recommended marker of central fat for cardiometabolic risk screening. Alternative surrogate markers have been recently proposed to better reflect the metabolic impact of central fat accumulation per se, based on WC normalization by height (Weight-to-Height Ratio - WtoH; Body Roundness Index - BRI) or body mass index (BMI) without (A Body Shape Index - ABSI) or with inclusion of plasma triglyceride and HDL-cholesterol concentrations (Visceral Adiposity Index - VAI). We investigated associations between WtoH, BRI, ABSI or VAI and insulin resistance (HOMA-index) or metabolic syndrome (MetS) in a general population cohort from the North-East Italy Mo.Ma. study (n=1965, age=49±13 years, BMI=26.7±5.2kg/m2). Baseline values were also evaluated as predictors of future insulin resistance and MetS in overweight-obese individuals undergoing 5-year follow-up (Ow-Ob) (n=263; age=54±9, BMI=30,7±4,1). Compared to WC or BMI, basal WtoH and BRI were similarly associated with baseline HOMA and MetS prevalence after multiple adjustments (P<0.001) and all markers similarly predicted 5-year HOMA and MetS (P<0.001). Under basal conditions, superimposable results were observed for VAI whereas ABSI was less accurate or unable to identify baseline HOMA and MetS (p<0.05 vs WtoH-BRI-VAI-WC-BMI). VAI had highest 5-year risk predictive value in Ow-Ob [ROC Area Under the Curve (AUC) VAI>WtoH-BRI-WC-BMI; p<0.05] while no predictive value was in contrast observed for ABSI (ROC AUC ABSI<WtoH-BRI-WC-BMI; p<0.05). Using alternate formulae with plasma lipid inclusion in ABSI and removal from VAI calculations completely reversed their 5-year predictive value and AUC. The current findings do not support replacement of WC with height-normalized anthropometric central fat surrogate markers to predict cardiometabolic risk in the general and overweight-obese population. BMI-normalization impairs risk assessment unless plasma lipid concentrations are available and included in calculations.

Effects Of High-fat Diet And Exercise On Total Plasma Macronutrient Contents By Fourier-transform Infrared Spectroscopy

High fat-low carbohydrate (HFLC) diets are increasingly considered by endurance athletes to enhance their performances and overall health. Total macronutrient contents in plasma may be affected by diets and exercise. PURPOSE: To examine the effects of HFLC diet and an acute bout of exercise on total plasma macronutrient contents in trained males. METHODS: Eight trained distance runners (age = 39.5±9.9 years and VO2max = 47.9±7.6 mL/kg/min) that were on high-carbohydrate (HC) diets adopted the HFLC diet for 3 weeks, which consisted of 70% of overall caloric intake from fats and no more than 50g of carbohydrates. At the end of each diet trial, participants performed an indoor treadmill exercise for 50 minutes at varying race paces followed by an outdoor 5-km time trial. Overnight fasting blood samples were collected at pre- (baseline) and post-exercise (24-hours) to analyze changes in total plasma lipids, proteins, and carbohydrates using attenuated total reflectance Fourier-transform infrared spectroscopy (ATR FT-IR). The O-H stretch vibrational band of water was used to normalize the IR spectra and the protein content was quantified by measuring the amide I peak intensity at 1600 - 1700 cm-1. To quantify the lipids and carbohydrates, the samples were lyophilized and measured by the intensities at 2800 - 3000 cm-1 and 800 - 1200 cm-1, respectively. RESULTS: The ATR FT-IR analysis showed that total plasma proteins remained unchanged (HC baseline = 135.20±4.20 and HFLC baseline = 135.24±3.91AU). However, the HC diet at baseline showed a significant accumulation of lipids (30.06±7.75 AU, 95% CI = 6.93) and carbohydrates (42.92±11.62 AU, 95% CI = 10.39). Additionally, total lipids in the HC diet significantly decreased at 24-hours post-exercise (from 30.06±7.75 to 28.51±7.91 AU, p=0.016). CONCLUSION: A short-term high-fat diet does not significantly alter any macronutrient contents in plasma, whereas a high-carbohydrate diet increases an accumulation of lipids and carbohydrates. Elevated plasma lipids and carbohydrates with a high-carbohydrate diet may be due to decreased insulin sensitivity, which consequently led to increased plasma lipid contents. Notably, decreased total plasma lipid content following an acute bout of exercise suggests that lipids were the primary energy substrate.

Associations of the plasma lipidome with mortality in the acute respiratory distress syndrome: a longitudinal cohort study

BackgroundIt is unknown if the plasma lipidome is a useful tool for improving our understanding of the acute respiratory distress syndrome (ARDS). Therefore, we measured the plasma lipidome of individuals with ARDS at two time-points to determine if changes in the plasma lipidome distinguished survivors from non-survivors. We hypothesized that both the absolute concentration and change in concentration over time of plasma lipids are associated with 28-day mortality in this population.MethodsSamples for this longitudinal observational cohort study were collected at multiple tertiary-care academic medical centers as part of a previous multicenter clinical trial. A mass spectrometry shot-gun lipidomic assay was used to quantify the lipidome in plasma samples from 30 individuals. Samples from two different days were analyzed for each subject. After removing lipids with a coefficient of variation > 30%, differences between cohorts were identified using repeated measures analysis of variance. The false discovery rate was used to adjust for multiple comparisons. Relationships between significant compounds were explored using hierarchical clustering of the Pearson correlation coefficients and the magnitude of these relationships was described using receiver operating characteristic curves.ResultsThe mass spectrometry assay reliably measured 359 lipids. After adjusting for multiple comparisons, 90 compounds differed between survivors and non-survivors. Survivors had higher levels for each of these lipids except for five membrane lipids. Glycerolipids, particularly those containing polyunsaturated fatty acid side-chains, represented many of the lipids with higher concentrations in survivors. The change in lipid concentration over time did not differ between survivors and non-survivors.ConclusionsThe concentration of multiple plasma lipids is associated with mortality in this group of critically ill patients with ARDS. Absolute lipid levels provided more information than the change in concentration over time. These findings support future research aimed at integrating lipidomics into critical care medicine.

Effect of high chronic intake of sucrose on liver metabolism in aging rats. Modulation by rutin and micronutrients.

High-sugar intake and senescence share common deleterious effects, in particular in liver, but combination of these two factors was little studied. Our aims were to examine the effect of a high-sucrose diet in liver of old rats and also the potential benefices of a polyphenol/micronutrient supplementation. Four groups of 22-month-old male rats fed during 5months with a diet containing either 13 or 62% sucrose, supplemented or not with rutin, vitamin E, A, D, selenium, and zinc were compared. We measured liver macronutrient composition, glycation/oxidative stress, enzyme activities (lipogenesis, β-oxidation, fructokinase), gene expression (enzymes and transcription factors), in vivo protein synthesis rates and plasma parameters. Sucrose induced an increase in plasma and liver lipid content, and a stimulation of liver protein synthesis rates. Gene expression was little changed by sucrose, with lower levels for LXR-α and LXR-β. Polyphenol/micronutrient supplementation tended to limit liver triglyceride infiltration through variations in fatty acid synthase, acyl coA oxidase, and possibly ATP-citrate lyase activities. In conclusion, despite differences in enzymatic regulations, and blunted responses of gene expression, high-sucrose diet was still able to induce a marked increase in liver lipid content in old animals. However, it probably attenuated the positive impact of polyphenol/micronutrients.

Genetic variation in human carboxylesterase CES1 confers resistance to hepatic steatosis

Obesity often leads non-alcoholic fatty liver disease, insulin resistance and hyperlipidemia. Expression of carboxylesterase CES1 is positively correlated with increased lipid storage and plasma lipid concentration. Here we investigated structural and metabolic consequences of a single nucleotide polymorphism in CES1 gene that results in p.Gly143Glu amino acid substitution. We generated a humanized mouse model expressing CES1WT (control), CES1G143E and catalytically dead CES1S221A (negative control) in the liver in the absence of endogenous expression of the mouse orthologous gene. We show that the CES1G143E variant exhibits only 20% of the wild-type lipolytic activity. High-fat diet fed mice expressing CES1G143E had reduced liver and plasma triacylglycerol levels. The mechanism by which decreased CES1 activity exerts this hypolipidemic phenotype was determined to include decreased very-low density lipoprotein secretion, decreased expression of hepatic lipogenic genes and increased fatty acid oxidation as determined by increased plasma ketone bodies and hepatic mitochondrial electron transport chain protein abundance. We conclude that attenuation of human CES1 activity provides a beneficial effect on hepatic lipid metabolism. These studies also suggest that CES1 is a potential therapeutic target for non-alcoholic fatty liver disease management.

Plasma Concentrations of Lutein and Zeaxanthin, Macular Pigment Optical Density, and Their Associations With Cognitive Performances Among Older Adults

We investigated the cross-sectional associations between macular pigment optical density (MPOD), plasma lutein (L), and zeaxanthin (Z) concentrations and cognitive function in 184 older adults of the 3-City-Bordeaux cohort. MPOD was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma L and Z (L+Z) concentrations were determined by high-performance liquid chromatography and were considered either crude or expressed as a ratio of the concentration of plasma lipids (total cholesterol [TC] + triglycerides [TG]). Cognitive performances were assessed using the following four separate neuropsychological tests: the Mini-Mental State Examination (MMSE), the Isaacs Set Test (IST), the Benton Visual Retention Test (BVRT), and the sum of the three free recalls of the Free and Cued Selective Reminding Test (FCSRT). These test results were summarized by a composite global cognitive z-score. Higher MPOD at 0.5° was significantly associated with a higher composite z-score (β = 0.15, 95% confidence interval [CI] 0.04-0.26), higher BVRT (β = 0.39, 95%CI 0.08-0.70), and higher IST (β = 1.16, 95%CI 0.11-2.22) performances. Higher plasma L+Z concentrations were significantly associated with higher IST scores (β = 0.97, 95%CI 0.01-1.94). Furthermore, a higher L+Z/TC+TG ratio was associated with a higher composite z-score (β = 0.12, 95%CI 0.01-0.23), along with higher IST (β = 1.02, 95%CI 0.002-2.04) and FCSRT (β = 1.55, 95%CI 0.41-2.69) performances. This analysis suggested that both higher MPOD and L+Z concentrations were significantly associated with higher cognitive performances. However, MPOD measurements have the advantage of being a fast and representative measure of long-term carotenoid intake.

Effect of long‐term administration of heat‐processed onion (Allium cepa L.) extract on body weight, visceral fat accumulation, and plasma lipid profile in C57BL/6 mice fed high‐fat diets

In the previous study, it was found that Amadori rearrangement compounds‐rich heat‐processed onion reduced postprandial blood glucose increase by reducing absorption of glucose through inhibition of sucrase and α‐glucosidase in the small intestinal tract. This reduced absorption of carbohydrate might control body weight gain due to excessive carbohydrates consumption and induce calorie restriction. To investigate and prove the mechanism for the effects of heat‐processed onion extract (ONI_V) on body weight gain, body weight, plasma lipids, body fat mass, and lipid deposition were evaluated and compared to Garcinia cambogia (GC), a known competitive inhibitor of adenosine 5′‐triphosphate (ATP) citrate lyase in C57BL/6 mice model. Male C57BL/6 mice were fed high‐fat diet (60% kcal fat) with 2% ONI_V or GC used as a positive control. Supplementation of ONI_V effectively lowered the body weight gain, visceral fat accumulation, and plasma lipid concentrations. Compared to control, ONI_V increased the number of adipocytes with a smaller diameter. Interestingly, GC treatment did not change either adipocyte numbers or sizes although total weight of visceral fat pads was significantly reduced compared to control. These results indicate that ONI_V and GC may use different mechanisms in inhibiting weight gain under the current experimental conditions used in this study. Furthermore, ONI_V may reduce weight gain using a similar mechanism of anti‐diabetic drugs, thiazolidinediones (TZDs). TZDs in humans and animals have been shown to be a strong ligand for PPARγ, a nuclear transcription factor that enhances adipocyte differentiation, thereby increasing the number of adipocytes with smaller diameters, which is consistent with the effects of ONI_V observed in this study. According to the obtained results, ONI‐V may be effective not only in reducing weight gains, but also in ameliorating some of the metabolic abnormalities including hyperglycemia, oxidative stress, and inflammation associated with weight gain and obesity.Support or Funding InformationThis research was financially supported by the Ministry of Trade, Industry, and Energy (MOTIE), Korea, under the “Regional Specialized Industry Development Program” supervised by the Korea Institute for Advancement of Technology (KIAT).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of Heated versus Thermoneutral Bikram Yoga Interventions on Endothelial Function and Arterial Stiffness

Bikram (hot) yoga is a style of hatha yoga practiced at 40.5° C with 40–60% relative humidity. We have previously documented improvements in endothelium‐dependent vasodilation but not arterial stiffness in healthy, middle‐aged adults with an 8‐week Bikram yoga intervention. Currently, it is unknown whether the effect of hot yoga on endothelial function might be attributed to the hatha yoga asanas or the high temperature/humidity. It is also unknown whether a longer intervention might produce significant alterations in arterial stiffness.PURPOSEThe purpose of this investigation was to determine the effects of a 12‐week Bikram yoga intervention performed in standard heated conditions and in a thermoneutral environment on endothelium‐dependent vasodilation and arterial stiffness.METHODSFifty‐two sedentary but apparently healthy adults aged 40–60 years were randomly assigned to one of three groups: Bikram yoga practiced at 40.5°C (n=19); Bikram yoga practiced at 23°C (n=14); or sedentary time‐control (n=19). The 12‐week yoga intervention consisted of 3 weekly 90‐minute Bikram yoga classes. The time control group was instructed to maintain current lifestyle patterns for the study duration. Body composition was determined via dual energy x‐ray absorptiometry (DXA). Endothelium‐dependent vasodilation was measured noninvasively using brachial artery flow‐mediated dilation (FMD) after 5 minutes of blood flow occlusion. Arterial stiffness was measured via brachial‐ankle pulse wave velocity (PWV).RESULTSAge, anthropometric variables, plasma lipid, glucose, and triglyceride concentrations, brachial artery FMD and brachial‐ankle PWV were not different among the three groups at baseline. Body fat percentage declined (p&lt;0.01) and total‐ (p=0.051) and LDL‐cholesterol (p =0.09) concentrations tended to decline only in the hot (40.5°C) yoga group. Brachial artery FMD increased (P&lt;0.05) in both yoga groups but brachial‐ankle PWV was not significantly altered in any group. There were no changes in any outcome variables in the time control group.CONCLUSIONSBikram yoga practiced in hot/humid and thermoneutral conditions produced similar improvements in endothelium‐dependent vasodilation in healthy, middle‐aged adults. The addition of the heat led to reductions in body fat percentage. Bikram yoga does not appear to modulate arterial stiffness in middle‐aged adults.Support or Funding InformationThis study was funded by Pure Action, Inc. Austin, TX, USAThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Regulation of Hepatic Glucose and Lipid Metabolism by the Acetyl‐CoA Hydrolase Acyl‐CoA Thioesterase 12 (Acot12)

Acetyl‐CoA is a key determinant of gluconeogenesis and lipid biosynthesis in the liver, and the sources of acetyl‐CoA within hepatocytes are well defined. Acot12 is a cytosolic enzyme that catalyzes the hydrolysis of acetyl‐CoA into acetate plus CoASH. In addition to its enzymatic domains, Acot12 also contains a steroidogenic acute regulatory protein‐related lipid transfer (START) domain, which functions as lipid sensor. Although enriched in the liver, the biological functions of Acot12 remain unknown. We hypothesized that Acot12 activity may suppress hepatic glucose production and lipogenesis.MethodsTo overexpress Acot12 in C57BL/6J mice and in primary cultured mouse hepatocytes, we generated Acot12.Ad adenovirus and used null.Ad adenovirus as the control. Expression levels of Acot12 were assessed by real‐time PCR, immunoblot analysis and immunofluorescence. Tolerance tests to glucose (GTTs), pyruvate (PTTs) and insulin (ITTs) were performed after 6, 16 and 4 h fasting periods, respectively. Plasma and hepatic lipid concentrations were measured using enzymatic assays. Rates of basal and cAMP‐stimulated rates of gluconeogenesis from pyruvate plus lactate, as well as de novo lipogenesis from acetate were determined in cultured hepatocytes. Fatty acid oxidation rates in liver tissue and primary hepatocytes were quantified from to the conversion of 14C‐palmitate into 14C‐acid soluble metabolites and 14C‐CO2.ResultsAcot12.Ad increased Acot12 mRNA and elevated protein levels by 10‐fold in mouse livers. Acot12 overexpression improved glucose tolerance, as evidence by decreased values of area‐under‐the curve (AUC) during the course of the GTTs. Decreased AUC values were also observed during PTTs, which reflect rates of gluconeogenesis. No differences were observed for ITTs, which largely reflect peripheral insulin responsiveness. Acot12 overexpression reduced hepatic phospholipids and plasma cholesterol concentrations. In primary hepatocytes, overexpression of Acot12 reduced basal and cAMP‐stimulated rates of glucose production, as well as rates of de novo lipogenesis. In addition, Acot12 overexpression increased fatty acid oxidation rates in both liver tissue and primary hepatocytes. This correlated with higher mRNA expression levels of the plasma membrane fatty acid transporter CD36 and of mitochondrial CPT1a, which promotes fatty acid uptake for oxidation.ConclusionsTaken together, our findings reveal that Acot12 activity in the liver suppresses both glucose production and lipogenesis. Increased rates of hepatocellular fatty acid uptake and oxidation presumably reflect compensatory mechanisms directed towards the repletion of TCA cycle intermediates that support glucose and lipid biosynthesis. We speculate that Acot12 regulates hepatic nutrient metabolism by controlling cytosolic acetyl‐CoA concentrations within the liver.Support or Funding InformationThis work was supported by NIH grants DK048873, DK056626 and DK103046, as well as the American Liver Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Antioxidant activity and Hypolipidemic effect of Ficus carica leaf and twig extracts in Triton WR-1339-induced hyperlipidemic mice

BACKGROUND/AIM: The hypolipidemic potential of both leaf and twig extracts of Ficus carica on experimental hyperlipidaemia induced by Triton WR-1339, in Swiss albino mice was investigated. In addition, the phenolic, flavonoid and anthocyanin contents of these extracts and their antioxidant activities were determined. These properties may have a synergistic effect on hyperlipidaemia. MATERIALS AND METHODS: Leaf and twig samples of F. carica were harvested and collected. The study of antioxidant activity of phenolic compounds was determined by the radical DPPH*, ABTS*+ and FRAP assays. The experimental design was carried out using acute oral toxicity study and Triton model hyperlipidaemia on Swiss albino adult male mice. The animals were observed continuously during the 14 days of the study for any physical signs of toxicity. On the 15th day, the animals were sacrificed by decapitation under anesthesia and the organs were observed for macroscopic pathological lesions. Hyperlipidaemia was induced in the mice by a single intravenous (iv) injection of Triton WR 1339 (300 mg/kg body weight), and the antihyperlipidemic effect of each extract, studied at 150 and 300 mg, was tested by gavage. After 24 hours of administration, serum from blood samples was used to estimate the various parameters of the lipid profile namely TC, TG, LDL and HDL. RESULTS: The results of the phenolic and flavonoid compounds of Ficus carica leaves and twigs varied from 12.84 to 19.78 mg gallic acid equivalents (GAE) and 5.02 to 9.72 mg EQ/g dry matter, respectively. The scavenging activity (IC50) against the radical DPPH* and ABTS*+ varied from 346.2 to 461.38 μg/mL and 288.3 to 369.01 μg/mL for twigs and leaves respectively, and from 50.82 to 54.2 μg/mL for FRAP assay. The acute toxicity study showed no mortality and clinical signs of toxicity in the tested doses. The LD50 value of extracts of twigs and leaves of Ficus carica is greater than 5000 mg/kg. The results revealed that the administration of Ficus carica (FC) leaf and twig extracts resulted in a significant (p &lt; 0.05) decline in levels of serum triglycerides, total cholesterol, LDL-c, and VLDL-c, while the serum high-density lipoprotein cholesterol was significantly increased. The decrease rate of the lipid parameters differs significantly (p &lt; 0.05) from the leaf and twig extracts and depends also on the administered dose. CONCLUSION: Ficus carica leaf and twig extracts may contain compounds able to lower plasma lipid concentrations, could contribute significantly to the total antioxidant properties and be beneficial in the treatment of hyperlipidaemia.

Nardostachys jatamansi DC Extract Alleviates Insulin Resistance and Regulates Glucose Metabolism in C57BL/KsJ-db/db Mice Through the AMP-Activated Protein Kinase Signaling Pathway.

This study investigated whether Nardostachys jatamansi DC extract (NJE) improved insulin sensitivity and suppressed hepatic glucose production in an animal model of type 2 diabetes. C57BL/KsJ-db/db mice were divided into three dietary groups: regular diet (control), NJE, and rosiglitazone. After 6 weeks of feeding, blood glucose, glycosylated hemoglobin, and plasma insulin levels were significantly lower in NJE than in diabetic control group mice. The oral glucose tolerance test also revealed a positive effect of NJE on increasing insulin sensitivity. The homeostatic index of insulin resistance was significantly lower in NJE than in diabetic control group mice. NJE markedly lowered the plasma lipid concentration compared to diabetic control group mice. In the skeletal muscle, the expression of phosphorylated AMP-activated protein kinase, pAkt substrate of 160 kDa, and plasma membrane glucose transporter type 4 increased more in NJE compared to diabetic control group mice. NJE also decreased the expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the liver. These findings demonstrate that NJE alleviates hyperglycemia by improving insulin sensitivity and inhibiting gluconeogenesis in the liver.

Endurance training and LXR activation increased LXRα and ABCA1 transcripts in Wistar male rats

Summary Purpose LXR, belongs to the ligands activated transcription factors, regulates the expression of genes in cholesterol homeostasis. The aim of the present study was to examine combinatory effects of selective LXR activator-T0901317 and training on gene expression profiles of LXRα and ABCA1. Material and methods To examine simultaneous effects of selective LXR activator-T0901317- and exercise on LXRα and ABCA1 genes expression and lipids profile, Wistar male rats were assigned to four groups as animal models: Control group (Ctrl), trained group received exercise (Exc) on a motor-driven treadmill at 28 meter/min for 60 min/day, 5 days/week for 8 weeks, group receiving LXR agonist T0901317 (10 mg kg−1 day−1) (Ago) for 1 week, group received both endurance training and LXR agonist T0901317 (Exc&Ago). Finally, rats were killed and blood was taken for lipids measurement. A portion of the liver was also excised for assessment of LXRα and ABCA1 transcripts. Results A significant increase in LXRα and ABCA1 transcripts was observed in Exc&Ago group when compared to other groups. However, there was not a synergistic response in plasma lipid and lipoprotein concentrations despite a significant increase in LXRα and ABCA1 mRNA levels, possibly due to a physiological negative feedback loop, the response to exercise could be negated by the effects of the agonist in plasma lipid and lipoprotein profiles.

A Diurnal Rhythm in Brown Adipose Tissue Causes Rapid Clearance and Combustion of Plasma Lipids at Wakening

Many favorable metabolic effects have been attributed to thermogenic activity of brown adipose tissue (BAT). Yet, time of day has rarely been considered in this field of research. Here, we show that a diurnal rhythm in BAT activity regulates plasma lipid metabolism. We observed a high-amplitude rhythm in fatty acid uptake by BAT that synchronized with the light/dark cycle. Highest uptake was found at the onset ofthe active period, which coincided with high lipoprotein lipase expression and low angiopoietin-like 4 expression by BAT. Diurnal rhythmicity in BAT activity determined the rate at which lipids were cleared from the circulation, thereby imposing the daily rhythm in plasma lipid concentrations. In mice as well as humans, postprandial lipid excursions were nearly absent at waking. We anticipate that diurnal BAT activity is an important factor to consider when studying the therapeutic potential of promoting BAT activity.

Increased plasma and adipose tissue levels of ANGPTL8/Betatrophin and ANGPTL4 in people with hypertension

BackgroundHypertension is a risk factor for both cardiovascular diseases (CVDs) and type 2 diabetes (T2D). Angiopoietin-like proteins (ANGPTLs), mainly ANGPTL3, ANGPTL4 and ANGPTL8, are associated with increased plasma lipid content due to their role in regulating the activity of lipoprotein lipase, a key enzyme in metabolism of the lipoprotein in circulation. Dyslipidaemia is a risk factor for hypertension development; however, the roles of ANGPTL3, ANGPTL4 and ANGPTL8 in subjects with hypertension have not yet been established. This study compared the plasma and adipose tissue levels of ANGPTL3, ANGPTL4 and ANGPTL8 in age- and body mass index-matched subjects with and without hypertension.MethodsA total of 119 subjects, including 69 hypertensive and 50 non-hypertensive subjects, were enrolled. ANGPTL3, ANGPTL4 and ANGPTL8 plasma levels were measured by ELISA, whereas their levels in adipose tissue were assessed via real-time PCR.ResultsWe found that ANGPTL4 (202.49 ± 17.44 ng/mL vs. 160.64 ± 10.36 ng/mL, p = 0.04) and ANGPTL8 levels (2310.96 ± 194.88 pg/mL vs. 1583.35 ± 138.27 pg/mL, p = 0.001) were higher in hypertensive subjects than non-hypertensive subjects. However, ANGPTL3 levels were not significantly different between the two populations. Similarly, ANGPTL4 and ANGPTL8 levels were also elevated in subjects with T2D and hypertension than in those with T2D but not hypertension. Additionally, people with highest tertiles of ANGPTL8 had higher odds of having hypertension (odd ratio [OR] = 3.8, 95% confidence interval [CI] = (1.5-9.8), p-Value = 0.005. Similar to its plasma levels, ANGPTL4 and ANGPTL8 were higher in adipose tissue.ConclusionsIn conclusion, our data illustrate that ANGPTL4 and ANGPTL8 levels in both plasma and adipose tissues are increased in subjects with hypertension. The elevated levels of ANGPTL4 and ANGPTL8 in hypertensive subjects highlight their potential involvement, their potential role as biomarkers for hypertension and their therapeutic value in hypertension given their roles in regulating lipid metabolism.