Glycyrrhizic acid suppresses early stage of adipogenesis through repression of MEK/ERK-mediated C/EBPβ and C/EBPδ expression in 3T3-L1 cells

Abstract

Glycyrrhizic acid (GA), a major constituent of the root of licorice (Glycyrrhiza glabra), and has various biological activities, including anti-obesity property. However, the molecular mechanism of anti-adipogenic effect of GA is still unclear. In this study, we investigated the anti-adipogenic effects of GA in mouse adipocytic 3T3-L1 cells and elucidated its underlying molecular mechanism. GA decreased the intracellular triglyceride level. The expression levels of the adipogenic and lipogenic genes were lowered by treatment with GA in a concertation-dependent manner. In contrast, GA did not affect the lipolytic gene expression and the released glycerol level. GA suppressed the early stage of adipogenesis when it was added for 0-3 h after initiation of adipogenesis. Moreover, GA reduced the mRNA levels of CCAAT/enhancer binding protein (C/EBP) β and C/EBPδ, both of which activate the early stage of adipogenesis. Furthermore, GA decreased phosphorylation of extracellular signal-regulated kinase [ERK: p44/42 mitogen-activated protein kinase (MAPK)] in the early stage of adipogenesis. In addition, a MAPK kinase (MEK) inhibitor, PD98059 reduced the C/EBPβ and C/EBPδ gene expression. These results indicate that GA suppressed the early stage of adipogenesis through repressing the MEK/ERK-mediated C/EBPβ and C/EBPδ expression in 3T3-L1 cells. Thus, GA has an anti-adipogenic ability and a possible agent for treatment of obesity.

Keywords: Adipocytes; C/EBPβ; C/EBPδ; Glycyrrhizic acid; MEK/ERK.