The direct effect of leptin on skeletal muscle thermogenesis is mediated by substrate cycling between de novo lipogenesis and lipid oxidation.
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.
Solinas
Giovanni
G
Department of Medicine, Division of Physiology, University of Fribourg, Switzerland.
Summermatter
Serge
S
Mainieri
Davide
D
Gubler
Marcel
M
Pirola
Luciano
L
Wymann
Matthias P
MP
Rusconi
Sandro
S
Montani
Jean-Pierre
JP
Seydoux
Josiane
J
Dulloo
Abdul G
AG
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
D020738:Leptin; D019869:Phosphatidylinositol 3-Kinases; D000263:Adenylate Kinase; D005947:Glucose