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Publication : Thyroid hormones are required for thermogenesis of beige adipocytes induced by Zfp423 inactivation.

First Author  Roth L Year  2024
Journal  Cell Rep Volume  43
Issue  12 Pages  114987
PubMed ID  39580797 Mgi Jnum  J:360816
Mgi Id  MGI:7852081 Doi  10.1016/j.celrep.2024.114987
Citation  Roth L, et al. (2024) Thyroid hormones are required for thermogenesis of beige adipocytes induced by Zfp423 inactivation. Cell Rep 43(12):114987
abstractText  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 TRbeta, 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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