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

IF 7.5 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2024-11-23 DOI:10.1016/j.celrep.2024.114987

Lisa Roth, Anne Hoffmann, Tobias Hagemann, Leonie Wagner, Christian Strehlau, Bilal Sheikh, Lorenz Donndorf, Adhideb Ghosh, Falko Noé, Christian Wolfrum, Knut Krohn, Juliane Weiner, John T Heiker, Nora Klöting, Michael Stumvoll, Anke Tönjes, Matthias Blüher, Jens Mittag, Kerstin Krause

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Abstract

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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Zfp423失活诱导的米色脂肪细胞产热需要甲状腺激素。

甲状腺激素（THs）在米色脂肪细胞产热过程中的意义仍未完全明了。我们曾报道，甲状腺激素直接调节脂肪组织中抗致热因子锌指蛋白423（ZFP423）的表达。本研究探讨了 THs 与肾上腺素能信号在调节生热能力和激活因 Zfp423 缺失而形成的米色脂肪细胞中的相互作用。我们证明，甲状腺激素是解偶联蛋白1（UCP1）依赖性产热不可或缺的因素，它能增加脂肪细胞特异性Zfp423基因敲除小鼠的能量消耗。甲状腺受体同工酶TRβ在腹股沟储库中发挥着核心作用，对它的靶向激活足以增强甲状腺功能减退的Zfp423iAKO小鼠的能量消耗。从机制上讲，THs和ZFP423途径合作调节早期B细胞因子2（EBF2）介导的Ucp1基因活化。对人类脂肪组织样本的 RNA 测序（RNA-seq）分析证实了这一调控网络与人类脂肪组织可塑性的相关性。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.