Capsicoside G, a furostanol saponin from pepper (Capsicum annuum L.) seeds, suppresses adipogenesis through activation of AMP-activated protein kinase in 3T3-L1 cells

The anti-adipogenic mechanism of capsicoside G in 3T3-L1 adipocytes was elucidated for the first time. Capsicoside G inhibited in a dose-dependent manner (1–20 µg/mL) the accumulation of lipid droplets in adipocytes without cytotoxicity. The major effects of capsicoside G on the inhibition of adipocyte differentiation were achieved by the early stage of adipogenesis. Treatment with capsicoside G inhibited the expression of the major adipogenic transcription factors and their target genes during differentiation of preadipocytes into adipocytes. Moreover, capsicoside G treatment significantly increased phosphorylation of 5′-adenosine monophosphate-activated protein kinase (AMPK) α1, thereby modulating fatty acid metabolism. In addition, the anti-adipogenic activity of capsicoside G was mediated by the activation of AMPK, as confirmed by using compound C, a highly selective inhibitor of AMPK, and the AMPKα1 small interfering RNA system. Capsicoside G from pepper seeds may have potential in the treatment of obesity.