Improvement of Insulin Sensitivity after Peroxisome Proliferator-Activated Receptor-α Agonist Treatment Is Accompanied by Paradoxical Increase of Circulating Resistin Levels
| Autor: | A. Horinek, Denisa Haluzikova, Daniel Housa, Z Vernerová, T. Kumstyrova, Haluzík M, Martin Haluzik, Zdeňka Lacinová, Marketa Dolinkova |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty medicine.medical_treatment Gene Expression Adipose tissue Receptors Cell Surface Fatty Acids Nonesterified Biology Mice Endocrinology Insulin resistance Fenofibrate Internal medicine Weight Loss Dietary Carbohydrates medicine Animals Insulin PPAR alpha Resistin Obesity RNA Messenger Muscle Skeletal Triglycerides Adiponectin Fatty liver Organ Size Glucose clamp technique medicine.disease Lipids Diet Fatty Liver Mice Inbred C57BL Adipose Tissue Liver Glucose Clamp Technique Insulin Resistance Receptors Adiponectin medicine.drug |
| Zdroj: | Endocrinology. 147:4517-4524 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2005-1624 |
| Popis: | We studied the effect of peroxisome proliferator-activated receptor-α (PPAR-α) 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-α 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-α 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|