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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)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
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
Language english
Publication Year 2024
HGF-reported in Year 2024
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Journal Cell Reports
Quellenangaben Volume: 43, Issue: 12, Pages: , Article Number: 114987 Supplement: ,
Publisher Cell Press
Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF-Topic(s) 30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-506501-001
G-554800-001
G-555000-001
G-506500-001
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)
DOI 10.1016/j.celrep.2024.114987
WOS ID 001364503700001
Scopus ID 85209920936
PubMed ID 39580797
Erfassungsdatum 2024-12-03
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