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Diepen, J.A. van, I.O.C.M. Vroegrijk, J.F.P. Berbée, S.E. Shoelson, J.A. Romijn, L.M. Havekes, P.C.N. Rensen and P. Voshol. 2011. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet. Am J Physiol Endocrinol Metab. 301:E1099-E1107.


DOI: 10.1152/ajpendo.00185.2011

Type of document: Journal Article

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More information on authors/freelancers connected to LBI :
Peter Voshol, PhD


Language of document: English

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

Abstract / summary in English:

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 plasmaderived 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.


Keywords in English: lipid metabolism; inflammation; very low-density lipoprotein, Type 2 Diabetes, Metabolic Syndrome, Pre-diabetes
Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet