Improvement of insulin sensitivity after peroxisome proliferator-activated receptor-α agonist treatment is accompanied by paradoxical increase of circulating resistin levels
Improvement of insulin sensitivity after peroxisome proliferator-activated receptor-α agonist treatment is accompanied by paradoxical increase of circulating resistin levels
复制标题
DOI：
10.1210/en.2005-1624
复制
发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Haluzik, M.
中科院分区：
文献类型：
--
作者：
Haluzik, M. M.;Lacinova, Z.;Haluzik, M.
我们研究了过氧化物酶体增殖物激活受体-α（PPAR-alpha）激活对正常小鼠和由生脂、简单碳水化合物饮食（LD）诱导的胰岛素抵抗小鼠血清中脂联素、脂联素和脂联素受体-1和-2（AdipoR 1和AdipoR 2）mRNA浓度和组织表达的影响。16周的LD喂养诱导肥胖伴肝脏脂肪变性和胰岛素水平升高，但对循环脂联素或脂联素无显著影响。用PPAR-alpha激动剂非诺贝特治疗降低了LD喂养小鼠的体重和脂肪垫重量，并改善了肝脏脂肪变性，同时降低了血糖、游离脂肪酸、甘油三酯、血清胰岛素水平和稳态模型评估指数值。正常血糖-高胰岛素钳夹试验显示LD喂养小鼠出现全身和肝脏胰岛素抵抗，非诺贝特可使其恢复正常。非诺贝特治疗显着增加循环中的两种饮食和脂联素水平的饮食喂养的小鼠。脂肪脂联素mRNA表达不受非诺贝特治疗的影响。非诺贝特治疗后，皮下脂肪抵抗素mRNA表达增加，但性腺脂肪不增加。除脂肪外，在肌肉中也表达了大量的脂联素mRNA。这种表达显着增加非诺贝特治疗后，在食物，但不是在LD喂养的小鼠。脂肪组织中AdipoR 1 mRNA的表达在LD喂养的小鼠中显著降低，在非诺贝特治疗后增加。总之，PPAR-alpha激活改善了LD喂养小鼠的胰岛素抵抗的发展，尽管血清β-内酰胺酶水平显著增加。这种效应可以部分解释为非诺贝特治疗后脂肪组织中AdipoR 1表达增加。
We studied the effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) activation on serum concentrations and tissue expression of resistin, adiponectin, and adiponectin receptor-1 and -2 (AdipoR1 and AdipoR2) mRNA in normal mice and mice with insulin resistance induced by lipogenic, simple-carbohydrate diet (LD). Sixteen weeks of LD feeding induced obesity with liver steatosis and increased insulin levels but did not significantly affect circulating adiponectin or resistin. Treatment with PPAR-alpha agonist fenofibrate decreased body weight and fat pad weight and ameliorated liver steatosis in LD-fed mice with concomitant reduction in blood glucose, free fatty acid, triglyceride, serum insulin levels, and homeostasis model assessment index values. Euglycemic-hyperinsulinemic clamp demonstrated the development of whole-body and liver insulin resistance in LD-fed mice, which were both normalized by fenofibrate. Fenofibrate treatment markedly increased circulating resistin levels on both diets and adiponectin levels in chow-fed mice only. Fat adiponectin mRNA expression was not affected by fenofibrate treatment. Resistin mRNA expression increased in subcutaneous but not gonadal fat after fenofibrate treatment. In addition to fat, a significant amount of adiponectin mRNA was also expressed in the muscle. This expression markedly increased after fenofibrate treatment in chow- but not in LD-fed mice. Adipose tissue expression of AdipoR1 mRNA was significantly reduced in LD-fed mice and increased after fenofibrate treatment. In conclusion, PPAR-alpha activation ameliorated the development of insulin resistance in LD-fed mice despite a major increase in serum resistin levels. This effect could be partially explained by increased AdipoR1 expression in adipose tissue after fenofibrate treatment.