title: Improvement of insulin sensitivity after peroxisome proliferator-activated receptor-alpha agonist treatment is accompanied by paradoxical increase of circulating resistin levels.
abstract: 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.
authors.affiliation: Third Department of Medicine, First Faculty of Medicine and General University Hospital, Charles University, 128 08 Prague, Czech Republic. mhalu@lf1.cuni.cz
authors.forename: M M
authors.initials: MM
authors.lastname: Haluzik
authors.forename: Z
authors.initials: Z
authors.lastname: Lacinova
authors.forename: M
authors.initials: M
authors.lastname: Dolinkova
authors.forename: D
authors.initials: D
authors.lastname: Haluzikova
authors.forename: D
authors.initials: D
authors.lastname: Housa
authors.forename: A
authors.initials: A
authors.lastname: Horinek
authors.forename: Z
authors.initials: Z
authors.lastname: Vernerova
authors.forename: T
authors.initials: T
authors.lastname: Kumstyrova
authors.forename: M
authors.initials: M
authors.lastname: Haluzik
mesh_terms: D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000273:Adipose Tissue / Q000737:chemistry / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004032:Diet; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005234:Fatty Liver / Q000097:blood / Q000188:drug therapy / Q000209:etiology; D011345:Fenofibrate / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D015309:Glucose Clamp Technique; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance; D008055:Lipids / Q000096:biosynthesis; D008099:Liver / Q000737:chemistry / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000737:chemistry; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000819:agonists* / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000235:genetics; D052243:Resistin / Q000097:blood* / Q000235:genetics; D014280:Triglycerides / Q000097:blood; D015431:Weight Loss / Q000187:drug effects
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D047493:PPAR alpha; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D052243:Resistin; D014280:Triglycerides; C475419:adiponectin receptor 1, mouse; C475421:adiponectin receptor 2, mouse; D011345:Fenofibrate