Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis
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 re...
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| Format: | Article |
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Wiley
2025-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408763 |
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| author | Xiaoping Wu Zixuan Zhang Jingjing Li Jiuyu Zong Lufengzi Yuan Lingling Shu Lai Yee Cheong Xiaowen Huang Mengxue Jiang Zhihui Ping Aimin Xu Ruby L.C. Hoo |
| author_facet | Xiaoping Wu Zixuan Zhang Jingjing Li Jiuyu Zong Lufengzi Yuan Lingling Shu Lai Yee Cheong Xiaowen Huang Mengxue Jiang Zhihui Ping Aimin Xu Ruby L.C. Hoo |
| author_sort | Xiaoping Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e7672d03cc404580a560a73090c08d5a |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-e7672d03cc404580a560a73090c08d5a2025-08-20T03:18:05ZengWileyAdvanced Science2198-38442025-04-011215n/an/a10.1002/advs.202408763Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue HomeostasisXiaoping Wu0Zixuan Zhang1Jingjing Li2Jiuyu Zong3Lufengzi Yuan4Lingling Shu5Lai Yee Cheong6Xiaowen Huang7Mengxue Jiang8Zhihui Ping9Aimin Xu10Ruby L.C. Hoo11State Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaDepartment of Rehabilitation Sciences Faculty of Health and Social Sciences Hong Kong Polytechnic University Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for Cancer Department of Hematological Oncology Sun Yat‐sen University Cancer Center ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaState Key Laboratory of Pharmaceutical Biotechnology The University of Hong Kong Hong Kong SAR ChinaAbstract 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.https://doi.org/10.1002/advs.202408763adipogenesisadipose tissue remodelingChchd10GSTA4NRF2obesity |
| spellingShingle | Xiaoping Wu Zixuan Zhang Jingjing Li Jiuyu Zong Lufengzi Yuan Lingling Shu Lai Yee Cheong Xiaowen Huang Mengxue Jiang Zhihui Ping Aimin Xu Ruby L.C. Hoo Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis Advanced Science adipogenesis adipose tissue remodeling Chchd10 GSTA4 NRF2 obesity |
| title | Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis |
| title_full | Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis |
| title_fullStr | Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis |
| title_full_unstemmed | Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis |
| title_short | Chchd10: A Novel Metabolic Sensor Modulating Adipose Tissue Homeostasis |
| title_sort | chchd10 a novel metabolic sensor modulating adipose tissue homeostasis |
| topic | adipogenesis adipose tissue remodeling Chchd10 GSTA4 NRF2 obesity |
| url | https://doi.org/10.1002/advs.202408763 |
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