Weisinger Richard S, Stanley Tracy K, Begg Denovan P, Weisinger Harrison S, Spark Kylie J, Jois Markandeya
School of Psychological Science, La Trobe University, Victoria 3086, Australia.
Physiol Behav. 2009 Aug 4;98(1-2):192-7. doi: 10.1016/j.physbeh.2009.05.009. Epub 2009 May 22.
The renin-angiotensin system (RAS) is functional within adipose tissue and angiotensin II, the active component of RAS, has been implicated in adipose tissue hypertrophy and insulin resistance. In this study, captopril, an angiotensin converting enzyme (ACE) inhibitor that prevents angiotensin II formation, was used to study the development of diet-induced obesity and insulin resistance in obesity prone C57BL/6J mice. The mice were fed a high fat diet (w/w 21% fat) and allowed access to either water or water with captopril added (0.2 mg/ml). Body weight was recorded weekly and water and food intake daily. Glucose tolerance was determined after 11-12 weeks. On completion of the study (after 16 weeks of treatment), the mice were killed and kidney, liver, epididymal fat and extensor digitorum longus muscle (EDL) were weighed. Blood samples were collected and plasma analysed for metabolites and hormones. Captopril treatment decreased body weight in the first 2 weeks of treatment. Food intake of captopril-treated mice was similar to control mice prior to weight loss and was decreased after weight loss. Glucose tolerance was improved in captopril-treated mice. Captopril-treated mice had less epididymal fat than control mice. Relative to body weight, captopril-treated mice had increased EDL weight. Relative to control mice, mice administered captopril had a higher plasma concentration of adiponectin and lower concentrations of leptin and non-esterified fatty acids (NEFA). The results indicate that captopril both induced weight loss and improved insulin sensitivity. Thus, captopril may eventually be used for the treatment of obesity and Type 2 diabetes.
肾素-血管紧张素系统（RAS）在脂肪组织中发挥作用，RAS的活性成分血管紧张素II与脂肪组织肥大和胰岛素抵抗有关。在本研究中，卡托普利是一种阻止血管紧张素II形成的血管紧张素转换酶（ACE）抑制剂，用于研究肥胖倾向的C57BL/6J小鼠饮食诱导的肥胖和胰岛素抵抗的发展。给小鼠喂食高脂肪饮食（重量比21%脂肪），并让它们饮用普通水或添加了卡托普利（0.2 mg/ml）的水。每周记录体重，每天记录水和食物摄入量。11 - 12周后测定葡萄糖耐量。研究结束时（治疗16周后），处死小鼠并称量肾脏、肝脏、附睾脂肪和趾长伸肌（EDL）的重量。采集血样并分析血浆中的代谢物和激素。卡托普利治疗在治疗的前2周使体重下降。在体重减轻之前，卡托普利治疗组小鼠的食物摄入量与对照组小鼠相似，体重减轻后食物摄入量减少。卡托普利治疗组小鼠的葡萄糖耐量得到改善。卡托普利治疗组小鼠的附睾脂肪比对照组小鼠少。相对于体重，卡托普利治疗组小鼠的EDL重量增加。相对于对照组小鼠，给予卡托普利的小鼠血浆中脂联素浓度较高，瘦素和非酯化脂肪酸（NEFA）浓度较低。结果表明，卡托普利既能诱导体重减轻又能改善胰岛素敏感性。因此，卡托普利最终可能用于治疗肥胖和2型糖尿病。
