Thyroid hormones are required for thermogenesis of beige adipocytes induced by Zfp423 inactivation
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.
Authors
- Adhideb Ghosh (ORCID: https://orcid.org/0000-0002-5160-4571)
- Anne Hoffmann (ORCID: https://orcid.org/0000-0003-3258-3397)
- Christian Wolfrum (ORCID: https://orcid.org/0000-0002-3862-6805)
- Christian Strehlau
- Kerstin Krause (ORCID: https://orcid.org/0000-0003-1766-3698)
- Knut Krohn (ORCID: https://orcid.org/0000-0001-8110-1273)
- Falko Noé (ORCID: https://orcid.org/0009-0002-3360-5455)
- Tobias Hagemann
- Michael Stümvoll (ORCID: https://orcid.org/0000-0001-6225-8240)
- Juliane Weiner (ORCID: https://orcid.org/0000-0003-1055-6005)
- Bilal N. Sheikh (ORCID: https://orcid.org/0000-0002-1970-6236)
- Nora Klöting (ORCID: https://orcid.org/0000-0002-7625-7254)
- Leonie Wagner
- Matthias Blüher (ORCID: https://orcid.org/0000-0003-0208-2065)
- John T. Heiker (ORCID: https://orcid.org/0000-0003-2822-3006)
- Jens Mittag (ORCID: https://orcid.org/0000-0001-7778-5158)
- Lisa Roth (ORCID: https://orcid.org/0000-0001-9357-1790)
- Anke Tönjes
- Lorenz Donndorf
Institutions
- Leipzig University of Applied Sciences (DE)
- Helmholtz Zentrum München (DE)
- ETH Zurich (CH)
- University Hospital Leipzig (DE)
- Deutsches Diabetes-Zentrum e.V. (DE)
- Heinrich Heine University Düsseldorf (DE)
- Leipzig University (DE)
- University of Lübeck (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-11-23
- DOI
- https://doi.org/10.1016/j.celrep.2024.114987
- Citations
- 5
- Primary Topic
- Adipose Tissue and Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Bundesministerium für Gesundheit
- Freistaat Sachsen