Haluzik M M, Lacinova Z, Dolinkova M, Haluzikova D, Housa D, Horinek A, Vernerova Z, Kumstyrova T, Haluzik M
Third Department of Medicine, First Faculty of Medicine and General University Hospital, Charles University, 128 08 Prague, Czech Republic.
Endocrinology. 2006 Sep;147(9):4517-24. doi: 10.1210/en.2005-1624. Epub 2006 Jun 1.
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.
我们研究了过氧化物酶体增殖物激活受体α（PPAR-α）激活对正常小鼠以及由生脂、简单碳水化合物饮食（LD）诱导的胰岛素抵抗小鼠血清中抵抗素、脂联素浓度和组织中脂联素受体-1和-2（AdipoR1和AdipoR2）mRNA表达的影响。16周的LD喂养诱导了肥胖并伴有肝脏脂肪变性，且胰岛素水平升高，但对循环脂联素或抵抗素无显著影响。用PPAR-α激动剂非诺贝特治疗可降低LD喂养小鼠的体重和脂肪垫重量，改善肝脏脂肪变性，同时降低血糖、游离脂肪酸、甘油三酯、血清胰岛素水平以及稳态模型评估指数值。正常血糖-高胰岛素钳夹试验表明，LD喂养小鼠出现了全身和肝脏胰岛素抵抗，而非诺贝特可使其恢复正常。非诺贝特治疗显著增加了两种饮食喂养小鼠的循环抵抗素水平，仅增加了正常饮食喂养小鼠的脂联素水平。非诺贝特治疗对脂肪组织脂联素mRNA表达无影响。非诺贝特治疗后，皮下脂肪而非性腺脂肪中的抵抗素mRNA表达增加。除脂肪外，肌肉中也表达大量脂联素mRNA。在正常饮食喂养的小鼠中，非诺贝特治疗后这种表达显著增加，而在LD喂养的小鼠中则未增加。LD喂养小鼠脂肪组织中AdipoR1 mRNA表达显著降低，非诺贝特治疗后增加。总之，尽管血清抵抗素水平大幅升高，但PPAR-α激活改善了LD喂养小鼠胰岛素抵抗的发展。这种作用可能部分归因于非诺贝特治疗后脂肪组织中AdipoR1表达增加。
