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cTAGE5 is essential for adipogenesis and adipose tissue development

Author

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  • Junwan Fan

    (Capital Medical University)

  • Tiantian Ma

    (Chinese Academy of Sciences)

  • Xiaoping Ren

    (Capital Medical University)

  • Zhilin Chang

    (Capital Medical University)

  • Dan Zhang

    (Chinese Academy of Sciences)

  • Yi Wang

    (Capital Medical University)

  • Shiyao Cheng

    (Capital Medical University
    Sun Yat-sen University)

  • Xin Qi

    (Capital Medical University)

  • Kehui Liu

    (Chinese Academy of Sciences)

  • Yan Wang

    (PLA General Hospital)

  • Yaqing Wang

    (Chinese Academy of Sciences)

  • Zhiheng Xu

    (Chinese Academy of Sciences
    Zhejiang University School of Medicine)

  • Wenyan He

    (Capital Medical University)

Abstract

White adipocytes serve as primary energy reservoirs and their malfunction is linked to different metabolic disorders, yet the mechanisms underlying cellular specialization, a critical step during adipogenesis remain unknown. Here, we reveal the indispensable role of cutaneous T-cell lymphoma-associated antigen 5 (cTAGE5) in adipocyte differentiation and maturation. Conditional deletion of cTAGE5 in adipocyte precursor cells (APCs), rather than mature adipocytes, results in progressive loss of white adipose tissue and death of mice. Mechanistically, cTAGE5 deficiency in APCs disturbs pro-insulin receptor (IR) processing and impairs insulin signaling, accompanied by significant down-regulation of actin cytoskeleton related genes and defect in cytoskeleton remodeling, alongside enhanced expression of proteins associated with lipid catabolic process and lipolysis in adipocytes. Importantly, inhibitors targeting actin polymerization and lipolysis effectively restore adipocyte differentiation capacity in cTAGE5-deficient APCs. Collectively, our findings demonstrate that cTAGE5 plays pivotal roles in adipogenesis and adipose tissue development.

Suggested Citation

  • Junwan Fan & Tiantian Ma & Xiaoping Ren & Zhilin Chang & Dan Zhang & Yi Wang & Shiyao Cheng & Xin Qi & Kehui Liu & Yan Wang & Yaqing Wang & Zhiheng Xu & Wenyan He, 2025. "cTAGE5 is essential for adipogenesis and adipose tissue development," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60698-1
    DOI: 10.1038/s41467-025-60698-1
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