Fischer, Katrin and Fenzl, Anna and Liu, Dianxin and Dyar, Kenneth A. and Kleinert, Maximilian and Brielmeier, Markus and Clemmensen, Christoffer and Fedl, Anna and Finan, Brian and Gessner, Andre and Jastroch, Martin and Huang, Jianfeng and Keipert, Susanne and Klingenspor, Martin and Bruening, Jens C. and Kneilling, Manfred and Maier, Florian C. and Othman, Ahmed E. and Pichler, Bernd J. and Pramme-Steinwachs, Ines and Sachs, Stephan and Scheideler, Angelika and Thaiss, Wolfgang M. and Uhlenhaut, Henriette and Ussar, Siegfried and Woods, Stephen C. and Zorn, Julia and Stemmer, Kerstin and Collins, Sheila and Diaz-Meco, Maria and Moscat, Jorge and Tschoep, Matthias H. and Mueller, Timo D. (2020) The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation. NATURE COMMUNICATIONS, 11 (1): 2306. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
During beta -adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to the nucleus to activate the expression of Ucp1 and Pgc-1 alpha. The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds to ATF2 to orchestrate activation of the Ucp1 enhancer and Pgc-1 alpha promoter. P62(Delta 69-251) mice show reduced expression of Ucp1 and Pgc-1 alpha with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1 alpha expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62(Delta 69-251) mice, global p62(-/-) and Ucp1-Cre p62(flx/flx) mice. BAT dysfunction resulting from p62 deficiency is manifest after birth and obesity subsequently develops despite normal food intake, intestinal nutrient absorption and locomotor activity. In summary, our data identify p62 as a master regulator of BAT function in that it controls the Ucp1 pathway through regulation of ATF2 genomic binding. Beta-adrenergic stimulation of brown adipose tissue leads to thermogenesis via the activating transcription factor 2 (ATF2) mediated expression of the thermogenic genes Ucp1 and Pgc-1 alpha. Here, the authors show that the scaffold protein p62 regulates brown adipose tissue function through modifying ATF2 genomic binding and subsequent Ucp1 and Pgc-1 alpha induction.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BROWN ADIPOSE-TISSUE; TRANSCRIPTION; KINASE; FAT; RESISTANCE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2021 10:06 |
| Last Modified: | 24 Mar 2021 10:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44589 |
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