MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose Tissue
Abstract Stimulating adipose tissue thermogenesis has emerged as a promising strategy for combating obesity, with uncoupling protein 1 (UCP1) playing a central role in this process. However, the mechanisms that suppress adipose thermogenesis and energy dissipation in obesity are not fully understood...
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| Format: | Article |
| Language: | English |
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Wiley
2025-05-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202416598 |
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| author | Xin‐Yuan Zhao Ben‐Chi Zhao Hui‐Lin Li Ying Liu Bei Wang An‐Qi Li Tian‐Shu Zeng Hannah Xiaoyan Hui Jia Sun Domagoj Cikes Nele Gheldof Jorg Hager Jian‐Xun Mi D. Ross Laybutt Yin‐Yue Deng Yan‐Chuan Shi G. Gregory Neely Qiao‐Ping Wang |
| author_facet | Xin‐Yuan Zhao Ben‐Chi Zhao Hui‐Lin Li Ying Liu Bei Wang An‐Qi Li Tian‐Shu Zeng Hannah Xiaoyan Hui Jia Sun Domagoj Cikes Nele Gheldof Jorg Hager Jian‐Xun Mi D. Ross Laybutt Yin‐Yue Deng Yan‐Chuan Shi G. Gregory Neely Qiao‐Ping Wang |
| author_sort | Xin‐Yuan Zhao |
| collection | DOAJ |
| description | Abstract Stimulating adipose tissue thermogenesis has emerged as a promising strategy for combating obesity, with uncoupling protein 1 (UCP1) playing a central role in this process. However, the mechanisms that suppress adipose thermogenesis and energy dissipation in obesity are not fully understood. This study identifies mitochondrial carrier homolog 2 (MTCH2), an obesity susceptibility gene, as a negative regulator of energy homeostasis across flies, rodents, and humans. Notably, adipose‐specific MTCH2 depletion in mice protects against high‐fat‐diet (HFD)‐induced obesity and metabolic disorders. Mechanistically, MTCH2 deficiency promotes energy expenditure by stimulating thermogenesis in brown adipose tissue (BAT) and browning of subcutaneous white adipose tissue (scWAT), accompanied by upregulated UCP1 protein expression, enhanced mitochondrial biogenesis, and increased lipolysis in BAT and scWAT. Using integrated RNA sequencing and proteomic analyses, this study demonstrates that MTCH2 is a key suppressor of thermogenesis by negatively regulating autophagy via Bcl‐2‐dependent mechanism. These findings highlight MTCH2's critical role in energy homeostasis and reveal a previously unrecognized link between MTCH2, thermogenesis, and autophagy in adipose tissue biology, positioning MTCH2 as a promising therapeutic target for obesity and related metabolic disorders. This study provides new opportunities to develop treatments that enhance energy expenditure. |
| format | Article |
| id | doaj-art-ad3a7da52244404eb47a93a2e90c1069 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-ad3a7da52244404eb47a93a2e90c10692025-08-20T02:56:11ZengWileyAdvanced Science2198-38442025-05-011217n/an/a10.1002/advs.202416598MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose TissueXin‐Yuan Zhao0Ben‐Chi Zhao1Hui‐Lin Li2Ying Liu3Bei Wang4An‐Qi Li5Tian‐Shu Zeng6Hannah Xiaoyan Hui7Jia Sun8Domagoj Cikes9Nele Gheldof10Jorg Hager11Jian‐Xun Mi12D. Ross Laybutt13Yin‐Yue Deng14Yan‐Chuan Shi15G. Gregory Neely16Qiao‐Ping Wang17Laboratory of Metabolism and Aging School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 ChinaLaboratory of Metabolism and Aging School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 ChinaLaboratory of Metabolism and Aging School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 ChinaLaboratory of Metabolism and Aging School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 ChinaLaboratory of Metabolism and Aging School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 ChinaLaboratory of Metabolism and Aging School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 ChinaWuhan Union Hospital Huazhong University of Science and Technology Wuhan 430022 ChinaSchool of Biomedical Sciences The Chinese University of Hong Kong Hong Kong 999077 ChinaDepartment of Endocrinology Zhujiang Hospital Southern Medical University Guangzhou 510280 ChinaInstitute of Physiology and Pathophysiology Johannes Kepler University Linz Linz 4020 AustriaEcole Polytechnique de Lausanne (EPFL) Lausanne CH‐1015 SwitzerlandNestlé Institute of Health Sciences Lausanne CH‐1015 SwitzerlandKey Laboratory of Big Data Intelligent Computing Chongqing University of Posts and Telecommunications Chongqing 400065 ChinaGarvan Institute of Medical Research St Vincent's Clinical School UNSW Sydney Darlinghurst Sydney NSW 2010 AustraliaSchool of Pharmaceutical Sciences (Shenzhen) Sun Yat‐sen University Shenzhen 518107 ChinaNeuroendocrinology Group Garvan Institute of Medical Research Darlinghurst Sydney NSW 2010 AustraliaThe Dr. John and Anne Chong Laboratory for Functional Genomics Charles Perkins Centre and School of Life & Environmental Sciences The University of Sydney Sydney NSW 2006 AustraliaLaboratory of Metabolism and Aging School of Pharmaceutical Sciences (Shenzhen) Shenzhen Campus of Sun Yat‐sen University Shenzhen 518107 ChinaAbstract Stimulating adipose tissue thermogenesis has emerged as a promising strategy for combating obesity, with uncoupling protein 1 (UCP1) playing a central role in this process. However, the mechanisms that suppress adipose thermogenesis and energy dissipation in obesity are not fully understood. This study identifies mitochondrial carrier homolog 2 (MTCH2), an obesity susceptibility gene, as a negative regulator of energy homeostasis across flies, rodents, and humans. Notably, adipose‐specific MTCH2 depletion in mice protects against high‐fat‐diet (HFD)‐induced obesity and metabolic disorders. Mechanistically, MTCH2 deficiency promotes energy expenditure by stimulating thermogenesis in brown adipose tissue (BAT) and browning of subcutaneous white adipose tissue (scWAT), accompanied by upregulated UCP1 protein expression, enhanced mitochondrial biogenesis, and increased lipolysis in BAT and scWAT. Using integrated RNA sequencing and proteomic analyses, this study demonstrates that MTCH2 is a key suppressor of thermogenesis by negatively regulating autophagy via Bcl‐2‐dependent mechanism. These findings highlight MTCH2's critical role in energy homeostasis and reveal a previously unrecognized link between MTCH2, thermogenesis, and autophagy in adipose tissue biology, positioning MTCH2 as a promising therapeutic target for obesity and related metabolic disorders. This study provides new opportunities to develop treatments that enhance energy expenditure.https://doi.org/10.1002/advs.202416598adipose tissueautophagymitochondrial carrier homolog 2 (MTCH2)obesitythermogenesis |
| spellingShingle | Xin‐Yuan Zhao Ben‐Chi Zhao Hui‐Lin Li Ying Liu Bei Wang An‐Qi Li Tian‐Shu Zeng Hannah Xiaoyan Hui Jia Sun Domagoj Cikes Nele Gheldof Jorg Hager Jian‐Xun Mi D. Ross Laybutt Yin‐Yue Deng Yan‐Chuan Shi G. Gregory Neely Qiao‐Ping Wang MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose Tissue Advanced Science adipose tissue autophagy mitochondrial carrier homolog 2 (MTCH2) obesity thermogenesis |
| title | MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose Tissue |
| title_full | MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose Tissue |
| title_fullStr | MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose Tissue |
| title_full_unstemmed | MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose Tissue |
| title_short | MTCH2 Suppresses Thermogenesis by Regulating Autophagy in Adipose Tissue |
| title_sort | mtch2 suppresses thermogenesis by regulating autophagy in adipose tissue |
| topic | adipose tissue autophagy mitochondrial carrier homolog 2 (MTCH2) obesity thermogenesis |
| url | https://doi.org/10.1002/advs.202416598 |
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