A functional role for the p62-ERK1 axis in the control of energy homeostasis and adipogenesis.
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.
Department of Cancer and Cell Biology, The Vontz Center for Molecular Studies, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267, USA.
Sang Jun
SJ
Lee
Paul T
PT
Pfluger
Ji Young
JY
Kim
Ruben
R
Nogueiras
Angeles
A
Duran
Gilles
G
Pagès
Jacques
J
Pouysségur
Matthias H
MH
Tschöp
Maria T
MT
Diaz-Meco
Jorge
J
Moscat
D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D000818:Animals; D002454:Cell Differentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008957:Models, Genetic; D009765:Obesity / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000378:metabolism*
C490981:Gtf2h1 protein, mouse; D007328:Insulin; D011994:Recombinant Proteins; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D048049:Extracellular Signal-Regulated MAP Kinases