Recent studies revealed that sirtuin 1 (SIRT1) is involved in the regulation of energy metabolism and its agonist resveratrol showed anti-obesity effect.This study aims to determine whether BTM0512,a novel derivative of resveratrol,acts as an antagonist of obesity and to explore its possible mechanisms.High-fat diet (HFD)-induced obese mice were intragastrically administered with BTM-0512 (5,10,and 20 mg/kg/day) or resveratrol (10mg/kg/day).It was found that the body weight,Lee’s index,ratio of visceral adipose tissue (VAT) to body weight,and blood glucose were significantly reduced in BTM-0512-treated mice when compared with those in mice treated with resveratrol.BTM-0512 up-regulated the expressions of SIRT1,full length PRDM 16 (fPRDM 16),total PRDM16 (tPRDM16,including fPPRDM16 and other PRDM16 isoforms),and uncoupling protein 1 (UCP1) in both brown and subcutaneous adipose tissues.Although BTM-0512 and resveratrol also up-regulated SIRT1 and tPRDM16 levels in VAT of HFD-induced obese mice,the expressions of fPRDM16,UCP1,and TMEM26 were down-regulated.In mouse primary subcutaneous preadipocytes cultured with or without adipogenic medium,BTM-0512 up-regulated fPRDM16,tPRDM16,and UCP1 expressions,which was reversed by SIRT1 antagonists.But in cultured brown and visceral adipocytes,the UCP1 protein level showed no significant change after treatment with 1 μM of BTM-0512.Moreover,transfection with human SIRT1 plasmid reduced lipid deposit,as well as the mRNA levels of fPRDM16,UCP1,and TMEM26,in cultured human visceral adipose-derived stem cells.In conclusion,BTM-0512 has stronger anti-obesity effect than resveratrol,which might be associated with activation of beige remodeling in subcutaneous adipose tissue.