Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/6/2009
Publication Date: 4/1/2009
Citation: Ejaz, A., Wu, D., Kwan, P.W., Meydani, M. 2009. Curcumin inhibits adipogenesis in 3T3-L1 adipocytes and angiogenesis and obesity in C57/BL mice. Journal of Nutrition. 139:919-925.
Interpretive Summary: Obesity as well as being overweight and disorders related to excessive weight have increased dramatically in the past twenty years. Obesity-related health problems such as heart disease and diabetes have increased the numbers of preventable deaths. Consequently, the prevention and treatment of obesity are critical to decrease illness and death. Obesity develops with the growth of adipose (fatty) tissue masses. Like growing tumors, adipose tissue requires new blood vessels to be formed, a process called angiogenesis. The blood vessels bring oxygen and nutrients to the expanding fat cells known as adipocytes. These adipocytes expand in size and number. One strategy to reduce the growth of fatty tissue masses would be to prevent the growth of the new blood vessels and to reduce the number and fat content of the fat cells. Using cell cultures and an animal model for obesity, we tested curcumin, a substance found in the spice turmeric. It has been shown to inhibit the formation of new blood vessels, decrease the transformation of young fat cells into mature fat cells, and reduce the build up of fat in the mature cells. All of these results contribute to less growth of fatty tissue and lower body weight gain and obesity—all of which was observed in the total body fat and body weight gain of the mice. Our results demonstrated for the first time that curcumin has the potential to prevent obesity due to its effect on the blood vessel (vascular) system and fat cells and fatty tissue.
Technical Abstract: The growth of new blood vessels or 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. In the present study, we examined the effect of curcumin, a polyphenol from turmeric, on angiogenesis and adipocyte development in cell culture systems and in mice fed a high fat diet. Curcumin in a dose-dependent manner (0-20 microM) suppressed differentiation of pre-adipocytes (3T3-L1) to mature adipocytes, at a low dose (5 microM) inhibited adipokine-induced angiogenesis of human umbilical vein endothelial cells (HUVEC) on Matrigel, and at high dose (20 microM) caused apoptosis of mature adipocytes. Supplementing high fat diet of mice with 500 mg curcumin/kg diet for 12 wks markedly reduced microvessels density in adipose tissue along with reduced expression of vascular endothelial growth factor (VEGF). Curcumin through activation of AMPK also down-regulated expression of GPAT enzyme, which reduces fatty acid esterification and adipogenesis as it was evident from the diminution of lipids accumulation in adipocytes in culture and reduction in total adiposity in mice fed high fat diet. In addition, activation of AMPK by curcumin resulted in inhibition of ACC and activation of CPT1 leading to overall increased fatty acid oxidation as it was manifested with the increase in 3H-palmitic acid oxidation. The in vivo effect of curcumin on these enzymes was also confirmed by RT-PCR in subcutaneous adipose tissue of mice fed high fat diet and supplemented with curcumin. These effects of curcumin on adipocyte metabolism was also evident by the presence of lower levels of blood triglycerides, cholesterol and glucose in mice fed high fat diet supplemented with curcumin. Dietary curcumin significantly lowered the expression level of PPAR-gamma and C/EBP-alpha, the two key transcription factors involved in adipogenesis and lipogenesis, in subcutaneous adipose tissue. The alteration in adipose tissue vascularity by curcumin together with its effect on lipid metabolism in adipocytes and its ability to suppress growth factors might have contributed to the total body fat reduction in supplemented mice. Our findings suggest for the first time that dietary curcumin supplementation may have potential health benefit effects in preventing obesity.