摘要：SummaryIdentification of safe and effective compounds to increase or activate UCP1 expression in brown or white adipocytes remains a potent therapeutic strategy to combat obesity. Here we reported that, glyburide, one of the FDA-approved drugs currently used to treat type 2 diabetes, can significantly enhance UCP1 expression in both brown and white adipocytes. Glyburide-fed mice exhibited a clear resistance to high-fat diet-induced obesity, reduced blood triglyceride level, and increased UCP1 expression in brown adipose tissue. Moreover,in situinjection of glyburide to inguinal white adipose tissue remarkably enhanced UCP1 expression and increased thermogenesis. Further mechanistic studies indicated that the glyburide effect in UCP1 expression in adipocytes was KATPchannel independent but may involve the regulation of the Ca2+-Calcineurin-NFAT signal pathway. Overall, our findings revealed the significant effects of glyburide in regulating UCP1 expression and thermogenesis in adipocytes, which can be potentially repurposed to treat obesity.Graphical AbstractDisplay OmittedHighlights•Glyburide significantly upregulated UCP1 expression in both brown and white adipocytes•Glyburide-fed mice exhibited a clear resistance to high-fat diet-induced obesity•The glyburide effect in UCP1 expression in adipocytes was KATPindependent•Glyburide effect in UCP1 level was reversed by the Calcineurin-NFAT pathway inhibitionHuman Metabolism; Molecular Biology
