Curcumin inhibits atherosclerosis by suppressing accumulation of lipids in macrophages in LDLr −/− mice

Abstract

Atherosclerosis is a multi-factorial disease of arteries where macrophages accumulate lipids and cholesterol through scavenger receptors and cytosolic fatty acid binding proteins (FABPs) leading to formation of foam cells. Knockout of FABP-4 or (aP2) gene attenuated the development of atherosclerosis in mice. Earlier we found that curcumin, a polyphenol from turmeric spice, down-regulated expression of aP2 in 3T3L-1 adipocytes and THP-1 macrophages and reduced accumulation of lipids in these cells in vitro. We hypothesized that dietary supplementation of curcumin in LDLr−/− mice may attenuate high fat diet–induced atherogenesis by suppressing aP2 expression, accumulation of lipids in macrophage and inflammatory cytokines. 8-wk old LDLr−/− mice were either fed control or high fat (HF; 20% w/w) diet supplemented with curcumin (0, 500, 1000, 1500 mg/kg diet) for 16 wks (n=24/group). Dietary curcumin supplementation had no effect on food intake and intestinal fat absorption, but significantly attenuated body wt. gain and adiposity (MRI) in HF-fed mice. Curcumin dose-dependently reduced accumulation of lipids in peritoneal macrophages of HF-fed mice. Analysis of atherosclerotic lesions in lumen of aortic tree revealed that dietary curcumin at 500 and 1000mg/kg diet significantly attenuated atherogenesis in HF-fed mice. Grant Funding Source: USDA Award 2010-65200-203945