title: Exercise improves insulin and leptin sensitivity in hypothalamus of Wistar rats.
abstract: Prolonged exercise of medium to high intensity is known to promote a substantial effect on the energy balance of rats. In male rats, moderately to severely intense programs lead to a reduction in food intake. However, the exact causes for the appetite-suppressive effects of exercise are not known. Here, we show that intracerebroventricular insulin or leptin infusion reduced food intake in exercised rats to a greater extent than that observed in control animals. Exercise was associated with a markedly increased phosphorylation/activity of several proteins involved in leptin and insulin signal transduction in the hypothalamus. The regulatory role of interleukin (IL)-6 in mediating the increase in leptin and insulin sensitivity in hypothalamus was also investigated. Treatment with insulin or leptin markedly reduced food intake in exercised rats that were pretreated with vehicle, although no increase in sensitivity to leptin- and insulin-induced anorexia after pretreatment with anti-IL-6 antibody was detected. The current study provides direct measurements of leptin and insulin signaling in the hypothalamus and documents increased sensitivity to these hormones in the hypothalamus of exercised rats in an IL-6-dependent manner. These findings provide support for the hypothesis that the appetite-suppressive actions of exercise may be mediated by the hypothalamus.
authors.affiliation: Department of Internal Medicine, State University of Campinas (UNICAMP), 13081-970-Campinas, SP, Brazil.
authors.forename: Marcelo B S
authors.initials: MB
authors.lastname: Flores
authors.forename: Maria Fernanda A
authors.initials: MF
authors.lastname: Fernandes
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Ropelle
authors.forename: Marcel C
authors.initials: MC
authors.lastname: Faria
authors.forename: Mirian
authors.initials: M
authors.lastname: Ueno
authors.forename: Lício A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Mario J A
authors.initials: MJ
authors.lastname: Saad
authors.forename: José B C
authors.initials: JB
authors.lastname: Carvalheira
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004789:Enzyme Activation; D007031:Hypothalamus / Q000502:physiology*; D007276:Injections, Intraventricular; D007328:Insulin / Q000097:blood / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6 / Q000502:physiology*; D053614:Janus Kinase 2; D020738:Leptin / Q000097:blood / Q000502:physiology*; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010750:Phosphoproteins / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000502:physiology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; C526296:Irs1 protein, rat; D020738:Leptin; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2