Roth, L.* ; Hoffmann, A. ; Hagemann, T. ; Wagner, L.* ; Strehlau, C. ; Sheikh, B. ; Donndorf, L. ; Ghosh, A.* ; Noé, F.* ; Wolfrum, C.* ; Krohn, K.* ; Weiner, J.* ; Heiker, J.T. ; Klöting, N. ; Stumvoll, M. ; Tönjes, A.* ; Blüher, M. ; Mittag, J.* ; Krause, K.*
Thyroid hormones are required for thermogenesis of beige adipocytes induced by Zfp423 inactivation.
Cell Rep. 43:114987 (2024)
The significance of thyroid hormones (THs) in beige adipocyte thermogenesis remains incompletely understood. We previously reported that THs directly regulate the expression of zinc-finger protein 423 (ZFP423), an anti-thermogenic factor, in adipose tissue. This study investigates the interaction between THs and adrenergic signaling in regulating thermogenic capacity and activation of beige adipocytes formed in response to Zfp423 deletion. We demonstrate that THs are indispensable for uncoupling protein 1 (UCP1)-dependent thermogenesis, leading to increased energy expenditure in mice with adipocyte-specific Zfp423 knockout. Targeted activation of the thyroid receptor isoform TRβ, which plays a central role in the inguinal depot, is sufficient to enhance energy expenditure in hypothyroid Zfp423iAKO mice. Mechanistically, THs and ZFP423 pathways cooperate to regulate early B cell factor 2 (EBF2)-mediated activation of the Ucp1 gene. RNA sequencing (RNA-seq) analysis of human adipose tissue samples supports the relevance of this regulatory network for human adipose tissue plasticity.
Altmetric
Additional Metrics?
Publication type
Article: Journal article
Document type
Scientific Article
Thesis type
Editors
Corresponding Author
Keywords
Cp: Metabolism ; Cp: Molecular Biology ; Ebf2 ; Ucp1 ; Zfp423 ; Adrenergic Signaling ; Beige Adipocytes ; Browning ; Norepinephrine ; Thermogenesis ; Thyroid Hormone Receptor Beta ; Thyroid Hormones; Brown Adipose-tissue; Transcriptional Control; White; Receptor; Triiodothyronine; Glucose; Activation; Conversion; Thyroxine; Obesity
Keywords plus
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
ISBN
Book Volume Title
Conference Title
Conference Date
Conference Location
Proceedings Title
Quellenangaben
Volume: 43,
Issue: 12,
Pages: ,
Article Number: 114987
Supplement: ,
Series
Publisher
Cell Press
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
University
University place
Faculty
Publication date
0000-00-00
Application date
0000-00-00
Patent owner
Further owners
Application country
Patent priority
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants
German Federal Ministry of Education and Research (BMBF) through the German Center for Diabetes Research (DZD e.V.)
Ministry of Culture and Science of the state of North Rhine-Westphalia (Dusseldorf, Germany)
German Federal Ministry of Health (Berlin, Germany)
Helmholtz Munich
Free State of Saxony
German Research Foundation (DFG)