2. Academic Validation
  3. Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis

Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis

  • Adv Sci (Weinh). 2025 Feb 22:e2408763. doi: 10.1002/advs.202408763.
Xiaoping Wu 1 2,  Zixuan Zhang 1 2,  Jingjing Li 3,  Jiuyu Zong 1 2,  Lufengzi Yuan 1 2,  Lingling Shu 1 4 5,  Lai Yee Cheong 1 5,  Xiaowen Huang 1 2,  Mengxue Jiang 1 2,  Zhihui Ping 1 2,  Aimin Xu 1 5,  Ruby L C Hoo 1 2
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong SAR, China.
  • 2 Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong SAR, China.
  • 3 Department of Rehabilitation Sciences, Faculty of Health and Social Sciences, Hong Kong Polytechnic University, Hong Kong SAR, China.
  • 4 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Department of Hematological Oncology, Sun Yat-sen University Cancer Center, China.
  • 5 Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.
PMID: 39985288 DOI: 10.1002/advs.202408763
Abstract

Dysregulation of adipose tissue (AT) homeostasis in obesity contributes to metabolic stress and disorders. Here, we identified that Coiled-coil-helix-coiled-coil-helix domain containing 10 (Chchd10) is a novel regulator of AT remodeling upon excess energy intake. Chchd10 is significantly reduced in the white adipose tissue (WAT) of mice in response to high-fat diet (HFD) feeding. AT-Chchd10 deficiency accelerates adipogenesis predominantly in subcutaneous AT of mice to store excess energy in response to short-term HFD feeding while upregulates Glutathione S-transferase A4 (GSTA4) to facilitate 4-HNE clearance mainly in visceral AT to prevent protein carbonylation-induced cell dysfunction after long-term HFD feeding. Hence, Chchd10 deficiency attenuates diet-induced obesity and related metabolic disorders in mice. Mechanistically, Chchd10 deficiency enhances adipogenesis and GSTA4 expression by activating TDP43/Raptor/p62/Keap1/NRF2 axis. Notably, the beneficial effect of Chchd10 deficiency is eliminated in hypertrophic adipocytes, where p62 is strikingly reduced. Collectively, Chchd10 is a metabolic sensor maintaining AT homeostasis, and the loss of p62 in adipose tissue under obese conditions impairs Chchd10-mediated AT remodeling.

Keywords

Chchd10; GSTA4; NRF2; TDP43; adipogenesis; adipose tissue remodeling; obesity; p62; protein carbonylation.

Figures
Products