Abstract:The effects of theophylline and theobromine on the body weight and insulin resistance of the mice fed with a high-fat diet（HFD）were studied.Fifty healthy C57BL/6J mice were selected and randomly divided into low-fat diet（LFD）group，LFD+theophylline group，LFD+theobromine group，high-fat diet（HFD）group，HFD+theophylline group，and HFD+theobromine group.The body mass，fasting blood glucose level，food intake，and water intake were recorded every week.The intraperitoneal glucose tolerance test（IPGTT）and intraperitoneal insulin tolerance test（IPITT）were performed at weeks 14 and 15.Organ indexes and serum biochemical indexes were determined at the end of the feeding treatment.The results showed that theophylline reduced the body mass by 4.89%-16.28% compared with the LFD group and by 7.86%-30.81% compared with the HFD group and inhibited fat accumulation.The results of IPGTT and IPITT showed that theophylline improved glucose tolerance and alleviated insulin resistance in mice.Compared with the HFD group，theophylline lowered the serum levels of total cholesterol，triglycerides，low-density lipoprotein，and alanine aminotransferase in mice，while theobromine did not exert these effects.In conclusion，although theophylline and theobromine，as methylxanthine alkaloids，are isomers of each other，their effects on weight loss and lipid reduction in HFD-induced mice are different.Theophylline can reduce the body mass gain and alleviate insulin resistance in HFD-induced mice，while theobromine did not show such effects.