Limonin counteracts obesity by activating thermogenesis in brown and white adipose tissues

Limonin is a tetracyclic triterpenoid compound enriched in citrus fruits. Whether it is effective against obesity and the underlying molecular mechanisms remain unknown. Herein, a high-fat diet (HFD) was given to male C57BL/6J mice for four weeks to induce obesity. After that, limonin (50 mg/kg) was orally administered to mice for another 8 weeks along with the HFD. Limonin treatment remarkably decreased fat mass and body weight gain, and simultaneously alleviated HFD-induced fatty liver and hyperlipidemia. Limonin prevented the whit-ening of brown adipose tissue (BAT) and promoted the browning of inguinal white adipose tissues (iWAT) in mice. Besides, the genes associated with thermogenesisincluding Ucp1, Fatp1 and Cpt1b and mitochondrial maker TOM20 were upregulated by limonin treatment in the BAT and iWAT. The promotion of thermogenic program was associated with the activation of PGC-1 alpha. Overall, these results demonstrate that limonin holds great po-tential for treating obesity by regulating energy balance.