ArticleCell death and differentiation2025
SOX4 facilitates brown fat development and maintenance through EBF2-mediated thermogenic gene program in mice.
Article in Cell death and differentiation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Oncogenic driver and therapeutic target: Prolactin signalling axis in retroperitoneal sarcoma.Clinical and translational medicine · 2026Article
- Decoding Adipose Tissue Phenotypic Switching: From Mechanisms to Computational Drug Discovery.Current obesity reports · 2026Review
- Transcription factor SOX4 promotes proliferation, invasion and lymphatic metastasis of laryngeal squamous cell carcinoma via PTBP2 activation.Frontiers in oncology · 2026Article
- Significance of neuroendocrine systems and the gut-brain axis (GBA) in the regulation of obesity.PeerJ · 2026Review
- Dual Role of Transcription Factors in the Development and Thermogenic Function of Brown Adipose Tissue.International journal of medical sciences · 2026Review
- The Artemisia argyi oil reduces high-fat diet-induced obesity by enhancing thermogenesis in brown adipose tissue.NPJ science of food · 2025Article
- The SOX4-Semaphorin3C axis promotes esophageal adenocarcinoma progression.Cancer letters · 2025Article
- Regulation of BAT thermogenesis via TRPA1-expressing hypothalamic POMC neurons.Animal cells and systems · 2025Article
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Authors and funding
17 authors.
Funding
Abstract
Brown adipose tissue (BAT) is critical for non-shivering thermogenesis making it a promising therapeutic strategy to combat obesity and metabolic disease. However, the regulatory mechanisms underlying brown fat formation remain incompletely understood. Here, we found SOX4 is required for BAT development and thermogenic program. Depletion of SOX4 in BAT progenitors (Sox4-MKO) or brown adipocytes (Sox4-BKO) resulted in whitened BAT and hypothermia upon acute cold exposure. The reduced thermogenic capacity of Sox4-MKO mice increases their susceptibility to diet-induced obesity. Conversely, overexpression of SOX4 in BAT enhances thermogenesis counteracting diet-induced obesity. Mechanistically, SOX4 activates the transcription of EBF2, which determines brown fat fate. Moreover, phosphorylation of SOX4 at S235 by PKA facilitates its nuclear translocation and EBF2 transcription. Further, SOX4 cooperates with EBF2 to activate transcriptional programs governing thermogenic gene expression. These results demonstrate that SOX4 serves as an upstream regulator of EBF2, providing valuable insights into BAT development and thermogenic function maintenance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.