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Nutrition and Disease

Curcumin Inhibits Adipogenesis in 3T3-L1 Adipocytes and Angiogenesis and Obesity in C57/BL Mice^1–3,

⁴ Vascular Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111 and ⁵ Department of Pathology, Tufts University School of Medicine, Boston, MA 02111

Angiogenesis is necessary for the growth of adipose tissue. Dietary polyphenols may suppress growth of adipose tissue through their antiangiogenic activity and by modulating adipocyte metabolism. We investigated the effect of curcumin, the major polyphenol in turmeric spice, on angiogenesis, adipogenesis, differentiation, apoptosis, and gene expression involved in lipid and energy metabolism in 3T3-L1 adipocyte in cell culture systems and on body weight gain and adiposity in mice fed a high-fat diet (22%) supplemented with 500 mg curcumin/kg diet for 12 wk. Curcumin (5–20 µmol/L) suppressed 3T3-L1 differentiation, caused apoptosis, and inhibited adipokine-induced angiogenesis of human umbilical vein endothelial cells. Supplementing the high-fat diet of mice with curcumin did not affect food intake but reduced body weight gain, adiposity, and microvessel density in adipose tissue, which coincided with reduced expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2. Curcumin increased 5'AMP-activated protein kinase phosphorylation, reduced glycerol-3-phosphate acyl transferase-1, and increased carnitine palmitoyltransferase-1 expression, which led to increased oxidation and decreased fatty acid esterification. The in vivo effect of curcumin on the expression of these enzymes was also confirmed by real-time RT-PCR in subcutaneous adipose tissue. In addition, curcumin significantly lowered serum cholesterol and expression of PPAR and CCAAT/enhancer binding protein , 2 key transcription factors in adipogenesis and lipogenesis. The curcumin suppression of angiogenesis in adipose tissue together with its effect on lipid metabolism in adipocytes may contribute to lower body fat and body weight gain. Our findings suggest that dietary curcumin may have a potential benefit in preventing obesity.

^* To whom correspondence should be addressed: E-mail: mohsen.meydani{at}tufts.edu.

Manuscript received 15 October 2008. Initial review completed 6 November 2008. Revision accepted 5 February 2009.

Published online 18 March 2009.