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Müller, T.D. ; Lee, S.J.* ; Jastroch, M. ; Kabra, D. ; Stemmer, K. ; Aichler, M. ; Abplanalp, B.* ; Ananthakrishnan, G.* ; Bhardwaj, N.* ; Collins, S.* ; Divanovic, S.* ; Endele, M. ; Finan, B. ; Gao, Y.* ; Habegger, K.M.* ; Hembree, J.* ; Heppner, K.M.* ; Hofmann, S. ; Holland, J.* ; Küchler, D. ; Kutschke, M. ; Krishna, R.* ; Lehti, M.* ; Oelkrug, R.* ; Ottaway, N.* ; Perez-Tilve, D.* ; Raver, C.* ; Walch, A.K. ; Schriever, S.C. ; Speakman, J.* ; Tseng, Y.H.* ; Diaz-Meco, M.* ; Pfluger, P.T. ; Moscat, J.* ; Tschöp, M.H.

P62 links β-adrenergic input to mitochondrial function and thermogenesis.

J. Clin. Invest. 123, 469-478 (2013)
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The scaffold protein p62 (sequestosome 1; SQSTM1) is an emerging key molecular link among the metabolic, immune, and proliferative processes of the cell. Here, we report that adipocyte-specific, but not CNS-, liver-, muscle-, or myeloid-specific p62-deficient mice are obese and exhibit a decreased metabolic rate caused by impaired nonshivering thermogenesis. Our results show that p62 regulates energy metabolism via control of mitochondrial function in brown adipose tissue (BAT). Accordingly, adipocyte-specific p62 deficiency led to impaired mitochondrial function, causing BAT to become unresponsive to β-adrenergic stimuli. Ablation of p62 leads to decreased activation of p38 targets, affecting signaling molecules that control mitochondrial function, such as ATF2, CREB, PGC1α, DIO2, NRF1, CYTC, COX2, ATP5β, and UCP1. p62 ablation in HIB1B and BAT primary cells demonstrated that p62 controls thermogenesis in a cell-autonomous manner, independently of brown adipocyte development or differentiation. Together, our data identify p62 as a novel regulator of mitochondrial function and brown fat thermogenesis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Brown Adipose-tissue ; P38 Map Kinase ; Activated Protein-kinase ; Transcriptional Control ; Adaptive Thermogenesis ; Insulin-resistance ; Cre Recombinase ; Adult Humans ; P62/sqstm1 ; Fat
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Quellenangaben Volume: 123, Issue: 1, Pages: 469-478 Article Number: , Supplement: ,
Publisher American Society of Clinical Investigation
Reviewing status Peer reviewed