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

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