Print Email Facebook Twitter Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet Title Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet Author van Diepen, J.A. 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. Publication year 2011 Abstract 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. Subject LifeMHR - Metabolic Health ResearchEELS - Earth, Environmental and Life SciencesBiologyHealthy LivingInflammationLipid metabolismVery low-density lipoproteinacetylsalicylic acidapolipoprotein C1immunoglobulin enhancer binding proteintranscription factor RelAtriacylglycerolvery low density lipoprotein cholesterolanimal experimentanimal modelarticlecholesterol blood levelcontrolled studydrug mechanismdrug targetingenzyme inhibitiongene expressionhypertriglyceridemiain vivo studylipid dietlipogenesislipoprotein blood levelmalemetabolic syndrome Xmousenonhumanpriority journalprotein expressionrisk factortriacylglycerol blood levelaspirin To reference this document use: http://resolver.tudelft.nl/uuid:cc6a3f8f-e9a3-4df6-892d-1ae2ca8541d5 DOI https://doi.org/10.1152/ajpendo.00185.2011 TNO identifier 445713 ISSN 0193-1849 Source American Journal of Physiology - Endocrinology and Metabolism, 301 (6), E1099-E1107 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.