关键词: 血管紧张素Ⅱ受体拮抗剂, 糖脂代谢, 棕色脂肪组织, 产热功能

Abstract: Objective  To study the effect and possible mechanism of angiotensin Ⅱ receptor blocker (ARB) on energy metabolism in mice.   Methods  ① Male 6-week-old C57BL/6N mice were fed with normal diet (ND) and high-fat diet (HFD) for 6 weeks, then detect their body weight and fasting blood glucose. ② The diabetic mice induced by high-fat diet were randomly divided into  control group (Con) and  drug treatment group (ARB). They were administered with saline and valsartan at a dose of 3 mg/kg per day via gastric lavage for 6 weeks. After that, the body weight, body temperature, intraperitoneal glucose tolerance test, respiratory metabolism rate, hematoxylin-eosin staining of adipose tissue, and the expression of thermogenesis-related genes in brown adipose tissue were examined. ③ By using male 6-week-old db/db mice as the experimental subjects, they were also administered with saline and valsartan at a dose of 3 mg/kg per day via gastric lavage for 5 weeks. After that, the body weight, fasting blood glucose, and body temperature were measured.   Results  High-fat diet successfully induced the diabetic mouse model. Valsartan treatment significantly reduced the weight gain rate of HFD mice and the body weight of db/db mice, increased the body temperature of HFD mice in a 4 ℃ cold environment, and improved the energy expenditure of HFD mice, but had no significant improvement on glucose metabolism in HFD mice. Compared with the control group, the fasting blood glucose level of db/db mice was significantly reduced after valsartan treatment, and the body temperature showed an upward trend after 2 h and 3 h of cold treatment at 4 ℃, but the difference was not statistically significant. In addition, for HFD mice, valsartan treatment significantly reduced the cell volume of brown adipocyte, subcutaneous adipocyte, and epididymal adipocyte. At the mRNA level, valsartan promoted the expression of UCP1 in brown adipose tissue, while the expression of Prdm16,PGC1α and AP2 expression did not change significantly.   Conclusions  Valsartan can improve energy metabolism in obese mice, and its mechanism may be related to the positive effects of ARB on the thermogenesis of brown adipose tissue.

Key words: angiotensin Ⅱ receptor antagonist, glycolipid metabolism, brown adipose tissue, thermogenesis