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The direct effect of leptin on skeletal muscle thermogenesis is mediated by substrate cycling between de novo lipogenesis and lipid oxidation
Author(s) -
Solinas Giovanni,
Summermatter Serge,
Mainieri Davide,
Gubler Marcel,
Pirola Luciano,
Wymann Matthias P.,
Rusconi Sandro,
Montani Jean-Pierre,
Seydoux Josiane,
Dulloo Abdul G.
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.10.066
Subject(s) - ampk , lipogenesis , thermogenesis , skeletal muscle , medicine , leptin , endocrinology , lipid metabolism , chemistry , protein kinase a , amp activated protein kinase , lipotoxicity , adipose tissue , biology , biochemistry , phosphorylation , insulin , insulin resistance , obesity
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.