title: Central leptin action improves skeletal muscle AKT, AMPK, and PGC1 alpha activation by hypothalamic PI3K-dependent mechanism.
abstract: Central leptin action requires PI3K activity to modulate glucose homeostasis and peripheral metabolism. However, the mechanism behind this phenomenon is not clearly understood. We hypothesize that hypothalamic PI3K activity is important for the modulation of the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway, PGC1 alpha, and AKT in skeletal muscle (SM). To address this issue, we injected leptin into the lateral ventricle of rats. Hypothalamic JAK2 and AKT were activated by intracerebroventricular (ICV) injection of leptin in a time-dependent manner. Central leptin improved tolerance to glucose (GTT), increased PGC1 alpha expression, and AKT, AMPK, ACC and JAK2 phosphorylation in the soleus muscle. Previous ICV administration of either LY294002 or propranolol (IP) blocked these effects. We concluded that the activation of the hypothalamic PI3K pathway is important for leptin-induced AKT phosphorylation, as well as for active catabolic pathway through AMPK and PGC1 alpha in SM. Thus, a defective leptin signalling PI3K pathway in the hypothalamus may contribute to peripheral resistance to insulin associated to diet-induced obesity.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas-UNICAMP, Campinas, SP, Brazil.
authors.forename: Erika A F R
authors.initials: EA
authors.lastname: Roman
authors.forename: Daniel
authors.initials: D
authors.lastname: Reis
authors.forename: Talita
authors.initials: T
authors.lastname: Romanatto
authors.forename: Denis
authors.initials: D
authors.lastname: Maimoni
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Ferreira
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Santos
authors.forename: Adriana S
authors.initials: AS
authors.lastname: Torsoni
authors.forename: Licio A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Marcio A
authors.initials: MA
authors.lastname: Torsoni
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D002867:Chromones / Q000378:metabolism; D004734:Energy Metabolism; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011433:Propranolol / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D055372:AMP-Activated Protein Kinases; D000319:Adrenergic beta-Antagonists; D002867:Chromones; D005947:Glucose; D007328:Insulin; D053614:Janus Kinase 2; D020738:Leptin; D009025:Morpholines; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011433:Propranolol; D051057:Proto-Oncogene Proteins c-akt; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C501429:Ppargc1a protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C507927:Jak2 protein, rat