title: The direct effect of leptin on skeletal muscle thermogenesis is mediated by substrate cycling between de novo lipogenesis and lipid oxidation.
abstract: We report here studies that integrate data of respiration rate from mouse skeletal muscle in response to leptin and pharmacological interference with intermediary metabolism, together with assays for phosphatidylinositol 3-kinase (PI3K) and AMP-activated protein kinase (AMPK). Our results suggest that the direct effect of leptin in stimulating thermogenesis in skeletal muscle is mediated by substrate cycling between de novo lipogenesis and lipid oxidation, and that this cycle requires both PI3K and AMPK signaling. This substrate cycling linking glucose and lipid metabolism to thermogenesis provides a novel thermogenic mechanism by which leptin protects skeletal muscle from excessive fat storage and lipotoxicity.
authors.affiliation: Department of Medicine, Division of Physiology, University of Fribourg, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Solinas
authors.forename: Serge
authors.initials: S
authors.lastname: Summermatter
authors.forename: Davide
authors.initials: D
authors.lastname: Mainieri
authors.forename: Marcel
authors.initials: M
authors.lastname: Gubler
authors.forename: Luciano
authors.initials: L
authors.lastname: Pirola
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Wymann
authors.forename: Sandro
authors.initials: S
authors.lastname: Rusconi
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Montani
authors.forename: Josiane
authors.initials: J
authors.lastname: Seydoux
authors.forename: Abdul G
authors.initials: AG
authors.lastname: Dulloo
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D005947:Glucose / Q000378:metabolism; D020738:Leptin / Q000008:administration & dosage / Q000502:physiology*; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction; D015219:Substrate Cycling; D022722:Thermogenesis
chemical_list: D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D000263:Adenylate Kinase; D005947:Glucose