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The effect of IL6-174C/G polymorphism on postprandial triglyceride metabolism in the GOLDN studyboxs.

ABSTRACT: Chronically elevated interleukin-6 (IL-6) affects lipid and lipoprotein metabolism. Individuals genetically predisposed to higher IL-6 secretion may be at risk of dyslipidemia, especially during the postprandial phase. We investigated the effect of genetic variants at the IL6 locus on postprandial lipemia in US Whites participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Subjects were given a single fat load composed of 3% of calories as protein, 14% as carbohydrate, and 83% as fat. Blood was drawn at 0 h, 3.5 h, and 6 h to determine plasma triglyceride (TG), TG-rich lipoprotein (TRL) and lipoprotein particle size. Homozygotes (GG) and heterozygotes (CG) of the -174C/G variant displayed higher plasma IL-6 concentrations compared with major allele homozygotes (CC) (P = 0.029). GG and CG subjects showed higher fasting plasma TG (P = 0.025), VLDL (P = 0.04), and large VLDL (P = 0.02) concentrations than did CC subjects. Moreover, GG and CG subjects experienced greater postprandial response of TG (P = 0.006) and TRL, including chylomicrons (P = 0.005), total VLDL (P = 0.029), and large VLDL (P = 0.017) than did CC subjects. These results suggest that the functional polymorphism -174C>G at the IL6 locus determines the difference in both fasting and postprandial TG metabolism. This phenomenon could be responsible for the observed association of this genetic variant with cardiovascular disease risk.

SUBMITTER: Shen J

PROVIDER: S-EPMC2444004 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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The effect of IL6-174C/G polymorphism on postprandial triglyceride metabolism in the GOLDN studyboxs.

Shen Jian J Arnett Donna K DK Pérez-Martínez Pablo P Parnell Laurence D LD Lai Chao-Qiang CQ Peacock James M JM Hixson James E JE Tsai Michael Y MY Straka Robert J RJ Hopkins Paul N PN Ordovás José M JM

Journal of lipid research 20080416 8

Chronically elevated interleukin-6 (IL-6) affects lipid and lipoprotein metabolism. Individuals genetically predisposed to higher IL-6 secretion may be at risk of dyslipidemia, especially during the postprandial phase. We investigated the effect of genetic variants at the IL6 locus on postprandial lipemia in US Whites participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Subjects were given a single fat load composed of 3% of calories as protein, 14% as carbohydrate, and ...[more]

PMID: 18420533

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Project description:The number of circulating endothelial progenitor cells (EPCs) predicts future development of atherosclerotic cardiovascular disease (ASCVD) and is reduced in patients with type 2 diabetes (T2DM) or impaired glucose tolerance (IGT). Recent studies revealed the contribution of tight control of glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as well as fatty acid oxidation in the regulation of stem cell behavior. In this study, we show that how dysregulated glucose and triglyceride metabolism in T2DM/IGT affects the homeostasis of EPCs, i.e. bone marrow stem/progenitor cells (BMSCs). In our clinical study, consistent with previous reports, the patients with IGT or T2DM showed reduced level of circulating EPCs, as compared normal glucose tolerance. On the other hand, fasting or postprandial hypertriglyceridemia (hTG) itself did not affect the level of circulating EPCs. However, further analysis using single and multiple regression analyses strongly suggested that, in the presence of postprandial hTG, postprandial hyperglycemia exerts devastating effect on EPC homeostasis. We therefore carried out the proof of concept study in mice. Our experimental study revealed that repetitive glucose+lipid (G+L) spikes, but not repetitive glucose (G) spikes or lipid (L) spikes, rapidly upregulated p53 in BMSCs and induced premature aging phenotype of bone marrow cells, i.e. the impairment of BMSC quiescence and function, and myeloid-biased differentiation. Subsequent analysis implicated that p53-mediated augmentation of mitochondrial OXPHOS plays pivotal role for the impairment of BMSC quiescence and function. On the other hand, it is still not clear how repetitive G+L injection induced myeloid-biased differentiation. Because cell-fate decisions are executed by transcription factors in response to extracellular signals, and the best-known function of p53 is as a transcription factor, we asked to what extent repetitive glucose spikes and repetitive glucose+TG spikes affect transcriptional regulation in LSK cells.

Dataset Information

The effect of IL6-174C/G polymorphism on postprandial triglyceride metabolism in the GOLDN studyboxs.

Publications

The effect of IL6-174C/G polymorphism on postprandial triglyceride metabolism in the GOLDN studyboxs.

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