Blockade of the renin-angiotensin system decreases adipocyte size with improvement in insulin sensitivity
Blockade of the renin-angiotensin system decreases adipocyte size with improvement in insulin sensitivity
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DOI：
10.1097/00004872-200410000-00021
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发表时间：
2004-10-01
影响因子：
4.9
通讯作者：
Shimamoto, K
中科院分区：
文献类型：
--
作者：
Furuhashi, M;Ura, N;Shimamoto, K
目的基于体外研究的结果，推测阻断肾素-血管紧张素系统（RAS）可促进前脂肪细胞的募集和分化，增加胰岛素敏感性小脂肪细胞的形成，抵消脂质的异位沉积，从而改善胰岛素敏感性。我们研究了RAS阻断对胰岛素敏感性，脂肪细胞大小和肌内脂质含量的果糖喂养的大鼠（FFR）作为一个模型的胰岛素抵抗hypertension.Design和方法6周龄的雄性Sprague-Dawley大鼠分为两组：那些喂养一个标准的食物（对照）和那些喂养了6周的果糖丰富的食物。在最后2周内，用溶剂或1 mg/kg/天的替莫普利（一种血管紧张素转换酶抑制剂）或0.1 mg/kg/天的奥美沙坦（一种血管紧张素II 1型受体阻滞剂）治疗FFR。胰岛素敏感性（M值：mg/kg/min）通过正常血糖高胰岛素葡萄糖钳夹法进行评估。结果与对照组相比，FFR组大鼠的M值降低，血压升高，脂肪细胞体积增大，附睾脂肪垫占体重的比例（%fat pads）升高，肌内甘油三酯升高。替莫普利和奥美沙坦均显著改善了M值，降低了血压和脂肪细胞大小，而FFR中的脂肪垫百分比未发生变化。脂肪细胞大小与M值呈负相关。治疗2周，但不显着，肌内triglycerid.Conclusions RAS封锁减少脂肪细胞的大小，而不改变附睾%脂肪垫伴随着胰岛素敏感性的改善。
Objective Based on results of in vitro studies, it has been hypothesized that blockade of the renin-angiotensin system (RAS) promotes the recruitment and differentiation of pre-adipocytes and that increased formation of small insulin-sensitive adipocytes counteracts ectopic deposition of lipids, thereby improving insulin sensitivity. We investigated the effect of RAS blockade on insulin sensitivity, adipocyte size, and intramuscular lipid content in fructose-fed rats (FFR) as a model of insulin-resistant hypertension.Design and methods Six-week-old male Sprague-Dawley rats were divided into two groups: those fed a standard chow (control) and those fed a fructose-rich chow for 6 weeks. FFR were treated with a vehicle or with 1 mg/kg per day of temocapril, an angiotensin-converting enzyme inhibitor, or 0.1 mg/kg per day of olmesartan, an angiotensin II type 1 receptor blocker, for the last 2 weeks. Insulin sensitivity (M value: mg/kg per min) was estimated by the euglycemic hyperinsulinemic glucose clamp method. Sizes of adipocytes derived from epididymal fat and triglyceride content in the soleus muscle were determined.Results FFR had lower M value, higher blood pressure, larger adipocyte size, higher ratio of epididymal fat pads over body weight (%fat pads), and higher intramuscular triglyceride than did the control rats. Both temocapril and olmesartan significantly improved the M value and decreased blood pressure and adipocyte size without change in %fat pads in FFR. Adipocyte size was negatively correlated with the M value. Treatment for 2 weeks decreased, but not significantly, intramuscular triglyceride.Conclusions RAS blockade decreases adipocyte size without change in epididymal %fat pads accompanied by improvement in insulin sensitivity.