18β-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

18 beta-Glycyrrhetinic acid (18 beta-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18 beta-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18 beta-GA dose-dependently (1-40 mu M) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 mu M of 18 beta-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18 beta-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18 beta-GA alters fat mass by directly affecting adipogenesis in maturing preadipocytes and lipolysis in matured adipocytes. Thus, 18 beta-GA may be useful for the treatment of obesity. (C) 2012 Elsevier Inc. All rights reserved.