The scaffold protein p62 regulates adaptive thermogenesis through ATF2 nuclear target activation

Katrin Fischer, Anna Fenzl, Dianxin Liu, Kenneth A. Dyar, Maximilian Kleinert, Markus Brielmeier, Christoffer Clemmensen, Anna Fedl, Brian Finan, Andre Gessner, Martin Jastroch, Jianfeng Huang, Susanne Keipert, Martin Klingenspor, Jens C. Brüning, Manfred Kneilling, Florian C. Maier, Ahmed E. Othman, Bernd J. Pichler, Ines Pramme-Steinwachs, Stephan Sachs, Angelika Scheideler, Wolfgang M. Thaiss, Henriette Uhlenhaut, Siegfried Ussar, Stephen C. Woods, Julia Zorn, Kerstin Stemmer, Sheila Collins, Maria Diaz-Meco, Jorge Moscat, Matthias H. Tschöp and Timo D. Müller ()
Additional contact information
Katrin Fischer: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Anna Fenzl: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Dianxin Liu: Vanderbilt University Medical Center
Kenneth A. Dyar: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Maximilian Kleinert: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Markus Brielmeier: Research Unit Comparative Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH
Christoffer Clemmensen: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Anna Fedl: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Brian Finan: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Andre Gessner: University Hospital Regensburg
Martin Jastroch: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Jianfeng Huang: Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute
Susanne Keipert: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Martin Klingenspor: Chair of Molecular Nutritional Medicine, Technical University of Munich, TUM School of Life Sciences Weihenstephan
Jens C. Brüning: Max Planck Institute for Metabolism Research
Manfred Kneilling: Eberhard Karls University Tübingen
Florian C. Maier: Eberhard Karls University Tübingen
Ahmed E. Othman: Eberhard Karls University Hospital Tübingen
Bernd J. Pichler: Eberhard Karls University Tübingen
Ines Pramme-Steinwachs: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Stephan Sachs: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Angelika Scheideler: Research Unit Comparative Medicine, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH
Wolfgang M. Thaiss: Eberhard Karls University Tübingen
Henriette Uhlenhaut: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Siegfried Ussar: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Stephen C. Woods: University of Cincinnati
Julia Zorn: University of Copenhagen
Kerstin Stemmer: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Sheila Collins: Vanderbilt University Medical Center
Maria Diaz-Meco: Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute
Jorge Moscat: Cancer Metabolism and Signaling Networks Program, Sanford Burnham Prebys Medical Discovery Institute
Matthias H. Tschöp: Helmholtz Zentrum München and German National Diabetes Center (DZD)
Timo D. Müller: Helmholtz Zentrum München and German National Diabetes Center (DZD)

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract During β-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-1α. 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-1α promoter. P62Δ69-251 mice show reduced expression of Ucp1 and Pgc-1α with impaired ATF2 genomic binding. Modulation of Ucp1 and Pgc-1α expression through p62 regulation of ATF2 signaling is demonstrated in vitro and in vivo in p62Δ69-251 mice, global p62−/− and Ucp1-Cre p62flx/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.

Date: 2020
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-16230-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16230-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-16230-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().