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ABCA1 gene variants regulate postprandial lipid metabolism in healthy men.

ABSTRACT: Genetic variants of ABCA1, an ATP-binding cassette (ABC) transporter, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly high-density lipoproteins and apolipoprotein A1; however, results from different studies have been inconsistent.To further characterize the effects of ABCA1 variants in human postprandial lipid metabolism, we studied the influence of 3 single nucleotide polymorphisms (i27943 [rs2575875]; i48168 [rs4149272]; R219K [rs2230806]) in the postprandial lipemia of 88 normolipidemic young men who were given a fatty meal. For i27943 and i48168 single nucleotide polymorphisms, fasting and postprandial values of apolipoprotein A1 were higher and postprandial lipemia was much lower in homozygotes for the major alleles, total triglycerides in plasma, and large triglyceride-rich lipoprotein triglycerides. These persons also showed a higher apolipoprotein A1/apolipoprotein B ratio. Major allele homozygotes for i48168 and i27943 showed additionally higher high-density lipoproteins and lower postprandial apolipoprotein B.Our work shows that major allele homozygotes for ABCA1 single nucleotide polymorphisms i27943 and i48168 have a lower postprandial response as compared to minor allele carriers. This finding may further characterize the role of ABCA1 in lipid metabolism.

SUBMITTER: Delgado-Lista J

PROVIDER: S-EPMC2878607 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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ABCA1 gene variants regulate postprandial lipid metabolism in healthy men.

Delgado-Lista Javier J Perez-Martinez Pablo P Perez-Jimenez Francisco F Perez-Jimenez Francisco F Garcia-Rios Antonio A Fuentes Francisco F Marin Carmen C Gómez-Luna Purificación P Camargo Antonio A Parnell Laurence D LD Ordovas Jose Maria JM Lopez-Miranda Jose J

Arteriosclerosis, thrombosis, and vascular biology 20100225 5

<h4>Objective</h4>Genetic variants of ABCA1, an ATP-binding cassette (ABC) transporter, have been linked to altered atherosclerosis progression and fasting lipid concentration, mainly high-density lipoproteins and apolipoprotein A1; however, results from different studies have been inconsistent.<h4>Methods and results</h4>To further characterize the effects of ABCA1 variants in human postprandial lipid metabolism, we studied the influence of 3 single nucleotide polymorphisms (i27943 [rs2575875]; ...[more]

PMID: 20185793

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Project description:Aims/hypothesisPrediabetes is associated with postprandial hypertriacylglycerolaemia. Resistance exercise acutely lowers postprandial plasma triacylglycerol (TG); however, the changes in lipid metabolism that mediate this reduction are poorly understood. The aim of this study was to identify the constitutive metabolic mechanisms underlying the changes in postprandial lipid metabolism after resistance exercise in obese men with prediabetes.MethodsWe evaluated the effect of a single bout of whole-body resistance exercise (seven exercises, three sets, 10-12 repetitions at 80% of one-repetition maximum) on postprandial lipid metabolism in ten middle-aged (50?±?9 years), overweight/obese (BMI: 33?±?3 kg/m2), sedentary men with prediabetes (HbA1c >38 but <48 mmol/mol [>5.7% but <6.5%]), or fasting plasma glucose >5.6 mmol/l but <7.0 mmol/l or 2 h OGTT glucose >7.8 mmol/l but <11.1 mmol/l). We used a randomised, crossover design with a triple-tracer mixed meal test (ingested [(13C4)3]tripalmitin, i.v. [U-13C16]palmitate and [2H5]glycerol) to evaluate chylomicron-TG and total triacylglycerol-rich lipoprotein (TRL)-TG kinetics. We used adipose tissue and skeletal muscle biopsies to evaluate the expression of genes regulating lipolysis and lipid oxidation, skeletal muscle respirometry to evaluate oxidative capacity, and indirect calorimetry to assess whole-body lipid oxidation.ResultsThe single bout of resistance exercise reduced the lipaemic response to a mixed meal in obese men with prediabetes without changing chylomicron-TG or TRL-TG fractional clearance rates. However, resistance exercise reduced endogenous and meal-derived fatty acid incorporation into chylomicron-TG and TRL-TG. Resistance exercise also increased whole-body lipid oxidation, skeletal muscle mitochondrial respiration, oxidative gene expression in skeletal muscle, and the expression of key lipolysis genes in adipose tissue.Conclusions/interpretationA single bout of resistance exercise improves postprandial lipid metabolism in obese men with prediabetes, which may mitigate the risk for cardiovascular disease and type 2 diabetes.

Project description:BackgroundEvidence is increasing that plant sterols and stanols not only lower fasting serum low-density lipoprotein concentrations, but also those of triglycerides (TG). Insight into effects of these components on postprandial TG metabolism, an emerging risk factor for cardiovascular disease, is missing.ObjectiveOur objective was to examine the 8-hour postprandial response after consuming plant sterol or stanol enriched margarine as part of a mixed meal.MethodsThis postprandial study was part of a randomized crossover study in which 42 subjects consumed plant sterol enriched (3 g/d plant sterols), plant stanol enriched (3 g/d plant stanols), and control margarines for 4 weeks. After each period, subjects consumed a shake enriched with 3g plant sterols (sterol period), 3g plant stanols (stanol period) or no addition (control period). Subjects received a second shake with no addition after 4 hours.ResultsTG and apoB48 incremental areas under the curves (iAUC) of the total (0-8h) and 1st meal response (0-4h) were comparable between the meals and in all age categories (I:18-35y, II:36-52y, III:53-69y). In subjects aged 53-69y, TG iAUC after the 2nd meal (4-8h) was higher in the stanol period as compared with the sterol (63.1±53.0 mmol/L/min; P < 0.01) and the control period (43.2±52.4 mmol/L/min; P < 0.05). ApoB48 iAUC after the 2nd meal was higher after the stanol than after the sterol period (67.1±77.0 mg/L/min; P < 0.05) and tended to be higher than after the control period (43.1±64.5 mg/L/min; P = 0.08) in subjects aged 53-69y. These increased postprandial responses may be due to reduced lipoprotein lipase activity, since postprandial apoCIII/II ratios were increased after stanol consumption compared with the control meal.ConclusionPostprandial TG and apoB48 responses are age-dependently increased after plant stanol consumption, which might be related to a changed clearance of triglyceride-rich lipoproteins.Trial registrationClinicalTrials.gov NCT01559428.

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ABCA1 gene variants regulate postprandial lipid metabolism in healthy men.

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ABCA1 gene variants regulate postprandial lipid metabolism in healthy men.

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