A functional role for the p62–ERK1 axis in the control of energy homeostasis and adipogenesis |
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| Authors: | Sang Jun Lee Paul T Pfluger Ji Young Kim Ruben Nogueiras Angeles Duran Gilles Pagès Jacques Pouysségur Matthias H Tschöp Maria T Diaz‐Meco Jorge Moscat |
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| Institution: | 1. Department of Cancer and Cell Biology, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, Ohio, 45267 USA;2. Department of Internal Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, Ohio, 45237 USA;3. Institute of Signaling, Developmental Biology and Cancer Research, CNRS UMR 6543, Université Nice, 33 Avenue de Valombrose, Nice, 06189 France |
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| Abstract: | In vivo genetic inactivation of the signalling adapter p62 leads to mature-onset obesity and insulin resistance, which correlate with reduced energy expenditure (EE) and increased adipogenesis, without alterations in feeding or locomotor functions. Enhanced extracellular signal-regulated kinase (ERK) activity in adipose tissue from p62-knockout (p62−/−) mice, and differentiating fibroblasts, suggested an important role for this kinase in the metabolic alterations of p62−/− mice. Here, we show that genetic inactivation of ERK1 in p62−/− mice reverses their increased adiposity and adipogenesis, lower EE and insulin resistance. These results establish genetically that p62 is a crucial regulator of ERK1 in metabolism. |
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| Keywords: | p62 sequestosome obesity ERK insulin |
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