Anti-obesity potential of Glycyrrhiza uralensis and licochalcone A through induction of adipocyte browning

Abstract

The main function of brown adipose tissue is to dissipate surplus caloric intake into heat energy by thermogenesis, increasing energy expenditure. Inducible brown adipocytes can develop within white adipose tissue (WAT) through a process referred to as browning. Browning of white fat represents a promising strategy for treatment of obesity and the related complications. We investigated whether Glycyrrhiza uralensis and its ingredients modulated adipogenesis through adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced obesity mice model. Amongst extracts and fractions of G. uralensis, methyl dichloride (MeCl2) fraction was the most effective to induce expression of uncoupling protein 1 (UCP1), a fat browning marker, in 3T3-L1 adipocytes. Ingredients of G. uralensis such as licochalcone A (LicoA), isoliquiritigenin, and liquiritigenin induced UCP1 expression in 3T3-L1 adipocytes. After inducing obesity in mice by 6-week HFD, MeCl2 fraction of G. uralensis or LicoA was intraperitoneally administered for additional 19 days. MeCl2 fraction or LicoA significantly reduced body weight gain and inguinal fat pad weights. Furthermore, MeCl2 fraction or LicoA improved metabolic disorders induced by HFD as the treatments decreased serum levels of glucose and cholesterol, and blocked insulin resistance. MeCl2 fraction or LicoA enhanced expression of brown fat markers such as UCP1, PRDM16, and PGC-1α and increased brown fat phenotype population in inguinal WAT of HFD-fed mice. Our results demonstrate that G. uralensis and LicoA are effective to reduce obesity and to recover metabolic homeostasis by inducing the brown fat phenotype.