-Lapachone Regulates Obesity through Modulating Thermogenesis in Brown Adipose Tissue and Adipocytes: Role of AMPK...

Activation of brown adipose tissue (BAT) has been proposed as a promising target against obesity due to its increased capacity for thermogenesis. In this study, we explored the effect of $$ -Lapachone ( $$ L), a compound obtained from the bark of the lapacho tree, against obesity. In vivo administration of $$ L into either high fat diet (HFD)-induced obese C57BL6 mice and genetically obese Lepr $$ mice prevented body weight gain, which was associated with tissue weight loss of white adipose tissue (WAT). In addition, $$ L elevated thermogenic proteins including uncoupling protein 1 (UCP1) and mitochondrial count in BAT and human adipose tissue-derived mesenchymal stem cells (hAMSCs). $$ L also induced AMP-activated protein kinase (AMPK) phosphorylation, subsequent upregulation of acetyl-CoA carboxylase (ACC) and UCP1, and these effects were diminished by AMPK inhibitor compound C, suggesting that AMPK underlies the effects of $$ L. Mitogen-activated protein kinase pathways participated in the thermogenesis of $$ L, specifically p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase 1/2 (ERK1/2) were activated by $$ L treatment in hAMSCs. Additionally, inhibitors of p38/JNK/ERK1/2 abrogated the activity of $$ L. Taken together, $$ L exerts anti-obese effects by inducing thermogenesis mediated by AMPK signaling pathway, suggesting that $$ L may have a potential therapeutic implication of obesity. Taken together, $$ L exerts anti-obese effects by not only inducing thermogenesis on brown adipocytes but also inducing the browning of white adipocytes. The anti-obese effect of $$ L is mediated by AMPK signaling pathway, suggesting that $$ L may have potential therapeutic implication of obesity.