Embelin attenuates adipogenesis and lipogenesis through activating canonical Wnt signaling and inhibits high-fat diet-induced obesity.

Abstract

Recent studies suggest that Embelin, a natural plant extract might have the potential to prevent body weight gain in rats. However, the mechanisms involved remain to be elucidated. Effects of Embelin on adipocyte differentiation and lipogenesis were studied in murine ST2 stromal cells and C3H10T1/2 mesenchymal cells. The mechanisms through which Embelin regulates adipogenic differentiation and lipogenesis were explored. The in vivo anti-obesity effects of Embelin in high-fat diet (HFD)-induced obesity mice and possible transcriptional impact were investigated. Embelin treatment suppressed ST2 and C3H10T1/2 cells to proliferate, and differentiate into mature adipocytes, along with the inhibition of adipogenic factors peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein-α, adipocyte protein 2 and adipsin. Embelin treatment also decreased the expression levels of lipogenic factors sterol regulatory element-binding protein 1, fatty acid synthase, acetyl-CoA carboxylase 1 and stearoyl-Coenzyme A desaturase 1. Embelin promoted the translocation of β-catenin from the cytoplasm into the nucleus in C3H10T1/2. The nuclear protein levels of β-catenin and TCF-4 were increased following Embelin treatment. Furthermore, Dickkopf-1 (Dkk1) expression was downregulated by Embelin, and overexpression of Dkk1 in C3H10T1/2 reversed the inhibition of adipogenesis and lipogenesis by Embelin. In vivo studies showed that Embelin treatment reduced the gain of body weight and fat, decreased the serum level of triglycerides, free fatty acid and total cholesterol, and improved glucose tolerance and insulin resistance in HFD-fed mice. Moreover, Embelin blocked induction of adipogenic and lipogenic factors and Dkk1 in adipose tissue in HFD-fed mice. The present work provides evidences that Embelin is effective in inhibiting adipogenesis and lipogenesis in vitro and the mechanisms may involve canonical Wnt signaling. Embelin has the potential to prevent body weight gain and fat accumulation, and to improve obesity-related glucose tolerance impairment and insulin resistance in the HFD-fed mice.