Esculetin, a coumarin derivative, suppresses adipogenesis through modulation of the AMPK pathway in 3T3-L1 adipocytes

• Esculetin inhibited lipid accumulation and the expression of adipogenic specific proteins.
• Esculetin increased phosphorylation of AMPK and acetyl-CoA carboxylase.
• Pretreatment with AMPK inhibitor abolished the inhibitory effects of esculetin on PPARγ expression.
• Esculetin has anti-adipogenic effects through modulation of PPARγ and C/EBPα via the AMPK signaling pathway.

Obesity is one of the most serious health problems in both Westernized and developing countries. AMP-activated protein kinase (AMPK) has emerged as a major regulator of appetite, body weight, and cellular energy balance. In this study, we investigated the effect of esculetin (ECT) on adipogenesis via activation of AMPK in 3T3-L1 cells. ECT markedly inhibited lipid accumulation and suppressed the expression of adipogenic specific proteins including peroxisome proliferator-activated receptors (PPARγ), CCAAT/enhancer binding protein a (C/EBPα), and adipocyte fatty acid binding protein (aP2). Moreover, ECT significantly increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and intracellular reactive oxygen species (ROS) production. However, pretreatment with compound C, a specific AMPK inhibitor, abolished the inhibitory effects of ECT on PPARγ and C/EBPα expression. Therefore, these results indicate that ECT has anti-adipogenic effects through modulation of PPARγ and C/EBPα via the AMPK signaling pathway.