Print Email Facebook Twitter Niacin reduces plasma CETP levels by diminishing liver macrophage content in CETP transgenic mice Title Niacin reduces plasma CETP levels by diminishing liver macrophage content in CETP transgenic mice Author Li, Z. Wang, Y. van der Sluis, R.J. van der Hoorn, J.W.A. Princen, H.M.G. van Eck, M. van Berkel, T.J.C. Rensen, P.C.N. Hoekstra, M. Publication year 2012 Abstract The anti-dyslipidemic drug niacin has recently been shown to reduce the hepatic expression and plasma levels of CETP. Since liver macrophages contribute to hepatic CETP expression, we investigated the role of macrophages in the CETP-lowering effect of niacin in mice. In vitro studies showed that niacin does not directly attenuate CETP expression in macrophages. Treatment of normolipidemic human CETP transgenic mice, fed a Western-type diet with niacin for 4 weeks, significantly reduced the hepatic cholesterol concentration (-20%), hepatic CETP gene expression (-20%), and plasma CETP mass (-30%). Concomitantly, niacin decreased the hepatic expression of CD68 (-44%) and ABCG1 (-32%), both of which are specific markers for the hepatic macrophage content. The decrease in hepatic CETP expression was significantly correlated with the reduction of hepatic macrophage markers. Furthermore, niacin attenuated atherogenic diet-induced inflammation in liver, as evident from decreased expression of TNF-alpha (-43%). Niacin similarly decreased the macrophage markers and absolute macrophage content in hyperlipidemic APOE*3-Leiden. CETP transgenic mice on a Western-type diet. In conclusion, niacin decreases hepatic CETP expression and plasma CETP mass by attenuating liver inflammation and macrophage content in response to its primary lipid-lowering effect, rather than by attenuating the macrophage CETP expression level. © 2012 Elsevier Inc. All rights reserved. Subject LifeMHR - Metabolic Health ResearchEELS - Earth, Environmental and Life SciencesBiomedical InnovationBiologyHealthy LivingCETPLipoproteinLiverMacrophagesNiacin To reference this document use: http://resolver.tudelft.nl/uuid:b54a9872-038a-410e-80fa-b46f8d140703 DOI https://doi.org/10.1016/j.bcp.2012.06.020 TNO identifier 463719 ISSN 0006-2952 Source Biochemical Pharmacology, 84 (6), 821-829 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.