Sanggenol F exerts anti-diabetic effects via promoting adipocyte differentiation and modifying adipokines expression

Adipose tissue is not only a lipid storage site, but also a well-known endocrine organ. Dysfunction of adipose tissue is associated with irregular lipid metabolism, ectopic lipid accumulation and Insulin resistance. It is proposed that modulating on adipose tissue is a reasonable way to ameliorate glucose and lipid metabolism. (±)-sanggenol F (SGF, purity >98.5%) was synthesized as a racemic mixture of natural (+)-sanggenol F. In this study, SGF was found to promote adipocyte differentiation, enhance Insulin sensitivity, and upregulate beneficial adipokines expression in 3T3-L1 cells. Furthermore, in vivo study showed that treatment with SGF for 4 weeks improved glucose metabolism, by decreasing fasting blood glucose and enhancing Insulin sensitivity. It also improved lipid metabolism, with reduced serum lipid level and ameliorated hepatic steatosis in db/db mice. During the process of target finding, we found that SGF had multiple activities of protein tyrosine Phosphatase 1B inhibition, Peroxisome Proliferator-activated Receptor γ and Peroxisome Proliferator-activated Receptor α agonism. These results showed the potential of SGF as a candidate for the therapy of type 2 diabetes.