Resveratrol promotes white adipocytes browning and improves metabolic disorders in Sirt1‐dependent manner in mice

Obesity has become an epidemic concern in modern society. The chronic obesity is associated with metabolic disorders, such as hyperglycemia, hyperlipidemia, fatty liver, and cadiovascular disease, which cause high risk for mortality. The novel potential strategy to overcome obesity is to "burn out" the extra fat via "browning" of the white adipose tissues. The phytochemical resveratrol (Res) has attracted substantial attention due to its powerful amelioratory effects in metabolic diseases. However, how Res regulates the browning of adipose tissues remains largely elusive. Our data show that the NAD+ -dependent deacetylase silent information regulator 1 (Sirt1) mediates Res-induced browning and fat reduction of adipocytes, as well as other Res-improved metabolic phenotypes including hyperglycemina and hyperlipidemia in mice. Interestingly, we found that the major metabolites of Res in vivo (Res-3-O-glucuronide, Res-4'-O-glucuronide, and Res-3-O-sulfate) were much less potent in promoting browning gene expressions and reducing fat content in comparison to Res itself in mouse and human adipocytes in vitro, suggesting the importance and necessarity to enhance the bioavailability of Res in vivo in consideration of therapeutic application. Taken together, our findings clarify the beneficial effects of Res on excess fat utilization via promotion of browning in a Sirt1-dependent manner, suggesting the potential therapeutic application of Res in the treatment of obesity and related metabolic disorders.