Dietary apple polyphenols promote fat browning in high-fat diet-induced obese mice through activation of adenosine monophosphate-activated protein kinase α

BACKGROUND Promoting brown and beige adipogenesis contributes to adaptive thermogenesis, which provides a defense against obesity and related disorders. Apple polyphenols (APs) play a significant role in treating variety of metabolic diseases. This study was conducted to determine the effects of APs on the development of brown and beige adipocytes and thermogenesis and investigate whether these effects are mediated by adenosine monophosphate-activated protein kinase (AMPK). High-fat diet (HFD)-induced obese mice and differentiated 3T3-L1 adipocytes were subjected to APs treatment. The thermogenic program and associated regulatory factors, and the involvement of AMPK alpha was assessed. RESULTS Dietary APs supplementation reduced adiposity and improved insulin sensitivity in HFD-induced obese mice. Moreover, APs increased the oxygen consumption and heat production and decreased respiratory exchange ratio, which were accompanied by the upregulation of thermogenic genes expression and the activation of AMPK alpha in brown fat and inguinal white fat. Further, APs treatment directly increased expression of brown adipogenic markers and induced phosphorylation of AMPK alpha in differentiated 3T3-L1 adipocytes, whereas the beneficial effects of APs were reversed by AMPK inhibition. CONCLUSION Our results provide new insights into the function of APs in regulating brown/beige adipogenesis and adaptive thermogenesis and suggest the potential application of APs in the prevention and therapeutics of obesity and associated metabolic diseases. (c) 2020 Society of Chemical Industry