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Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet

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Author: Diepen, J.A. van · Vroegrijk, I.O.C.M. · Berbée, J.F.P. · Shoelson, S.E. · Romijn, J.A. · Havekes, L.M. · Rensen, P.C.N. · Voshol, P.J.
Source:American Journal of Physiology - Endocrinology and Metabolism, 6, 301, E1099-E1107
Identifier: 445713
doi: doi:10.1152/ajpendo.00185.2011
Keywords: Biology · Inflammation · Lipid metabolism · Very low-density lipoprotein · acetylsalicylic acid · apolipoprotein C1 · immunoglobulin enhancer binding protein · transcription factor RelA · triacylglycerol · very low density lipoprotein cholesterol · animal experiment · animal model · article · cholesterol blood level · controlled study · drug mechanism · drug targeting · enzyme inhibition · gene expression · hypertriglyceridemia · in vivo study · lipid diet · lipogenesis · lipoprotein blood level · male · metabolic syndrome X · mouse · nonhuman · priority journal · protein expression · risk factor · triacylglycerol blood level · aspirin · Healthy Living · Life · MHR - Metabolic Health Research · EELS - Earth, Environmental and Life Sciences


Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-?B activity but also reduces hypertriglyceridemia in humans. The aim of this study was to investigate the mechanism by which aspirin improves hypertriglyceridemia. Human apolipoprotein CI (apoCI)-expressing mice (APOC1 mice), an animal model with elevated plasma triglyceride (TG) levels, as well as normolipidemic wild-type (WT) mice were fed a high-fat diet (HFD) and treated with aspirin. Aspirin treatment reduced hepatic NF-?B activity in HFD-fed APOC1 and WT mice, and in addition, aspirin decreased plasma TG levels (-32%, P < 0.05) in hypertriglyceridemic APOC1 mice. This TG-lowering effect could not be explained by enhanced VLDL-TG clearance, but aspirin selectively reduced hepatic production of VLDL-TG in both APOC1 (-28%, P < 0.05) and WT mice (-33%, P < 0.05) without affecting VLDL-apoB production. Aspirin did not alter hepatic expression of genes involved in FA oxidation, lipogenesis, and VLDL production but decreased the incorporation of plasma-derived FA by the liver into VLDL-TG (-24%, P < 0.05), which was independent of hepatic expression of genes involved in FA uptake and transport. We conclude that aspirin improves hypertriglyceridemia by decreasing VLDL-TG production without affecting VLDL particle production. Therefore, the inhibition of inflammatory pathways by aspirin could be an interesting target for the treatment of hypertriglyceridemia. © 2011 the American Physiological Society.