title: Acute exercise suppresses hypothalamic PTP1B protein level and improves insulin and leptin signaling in obese rats.
abstract: Hypothalamic inflammation is associated with insulin and leptin resistance, hyperphagia, and obesity. In this scenario, hypothalamic protein tyrosine phosphatase 1B (PTP1B) has emerged as the key phosphatase induced by inflammation that is responsible for the central insulin and leptin resistance. Here, we demonstrated that acute exercise reduced inflammation and PTP1B protein level/activity in the hypothalamus of obese rodents. Exercise disrupted the interaction between PTP1B with proteins involved in the early steps of insulin (IRβ and IRS-1) and leptin (JAK2) signaling, increased the tyrosine phosphorylation of these molecules, and restored the anorexigenic effects of insulin and leptin in obese rats. Interestingly, the anti-inflammatory action and the reduction of PTP1B activity mediated by exercise occurred in an interleukin-6 (IL-6)-dependent manner because exercise failed to reduce inflammation and PTP1B protein level after the disruption of hypothalamic-specific IL-6 action in obese rats. Conversely, intracerebroventricular administration of recombinant IL-6 reproduced the effects of exercise, improving hypothalamic insulin and leptin action by reducing the inflammatory signaling and PTP1B activity in obese rats at rest. Taken together, our study reports that physical exercise restores insulin and leptin signaling, at least in part, by reducing hypothalamic PTP1B protein level through the central anti-inflammatory response.
authors.affiliation: School of Applied Science, University of Campinas (UNICAMP Limeira, São Paulo, Brazil.
authors.forename: Eloize C
authors.initials: EC
authors.lastname: Chiarreotto-Ropelle
authors.forename: Luciana S S
authors.initials: LS
authors.lastname: Pauli
authors.forename: Carlos K
authors.initials: CK
authors.lastname: Katashima
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Pimentel
authors.forename: Paty K
authors.initials: PK
authors.lastname: Picardi
authors.forename: Vagner R R
authors.initials: VR
authors.lastname: Silva
authors.forename: Claudio T
authors.initials: CT
authors.lastname: de Souza
authors.forename: Patrícia O
authors.initials: PO
authors.lastname: Prada
authors.forename: Dennys E
authors.initials: DE
authors.lastname: Cintra
authors.forename: José B C
authors.initials: JB
authors.lastname: Carvalheira
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Ropelle
authors.forename: José R
authors.initials: JR
authors.lastname: Pauli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003345:Corticosterone / Q000652:urine; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism*; D007150:Immunohistochemistry; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000201:enzymology / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms
chemical_list: D007328:Insulin; D015850:Interleukin-6; D020738:Leptin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D003345:Corticosterone
keywords: exercise; hypothalamus; insulin; leptin; obesity