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

Abstract

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 micromol/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 PPARgamma and CCAAT/enhancer binding protein alpha, 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.

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…Curcumin, a polyphenol occurring in turmeric with potent anti-inflammatory activity, is one of the natural compounds that have more potential as antiobesity treatment since, in vitro, is able to suppress 3T3-L1 differentiation and cause apoptosis (Ejaz et al, 2009). …”

“…In HFD-fed mice, curcumin supplementation reduces body weight gain and adiposity probably by increasing oxidation and by decreasing fatty acid esterification in adipose tissue (Ejaz et al, 2009). In HFD-fed rats, the beneficial effect of curcumin is mediated by attenuating lipogenic gene expression in the liver and the inflammatory response in the adipose tissue (Shao et al, 2012).…”

Angiogenesis and development of adipose tissue

“…Supplementing the high-fat diet of mice with curcumin reduced body weight gain, adiposity, and microvessel density in adipose tissue, which coincided with reduced expression of VEGF and VEGFR-2. Curcumin also had a beneficial effect on lipid metabolism (Ejaz et al, 2009). …”

Oleuropein as an inhibitor of peroxisome proliferator-activated receptor gamma

“…Many experiments with the polyphenols demonstrated substantial modulation of physiological and molecular pathway involved in energy metabolism and adiposity (reviewed in (Meydani and Hasan 2010)). Catechins from green tea (Lin et al 2005), resveratrol from red grapes (Floyd et al 2008) and curcumin from curcuma (Ejaz et al 2009) suppressed adipogenesis on 3T3-L1 cell line through several mechanisms including attenuation of peroxisome proliferator-activated receptor c (PPARc) regulatory pathway (Manach et al 2004). Also, the olive tree, botanically known as Olea europaea, and its products are a source of at least 30 phenolic compounds, and particularly, extra-virgin olive oil contains considerable amounts of phenolic compounds, e.g., oleuropein and its hydrolysis product hydroxytyrosol, which are responsible for its peculiar taste and high stability.…”