cTAGE5 is essential for adipogenesis and adipose tissue development

Junwan Fan (), Tiantian Ma, Xiaoping Ren, Zhilin Chang, Dan Zhang, Yi Wang, Shiyao Cheng, Xin Qi, Kehui Liu, Yan Wang, Yaqing Wang, Zhiheng Xu () and Wenyan He ()
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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
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
Wenyan He: Capital Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-60698-1

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