TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3
Abstract In mammals, the activation of thermogenic adipocytes, such as beige and brown adipocytes, can significantly increase overall energy expenditure, offering a promising strategy to combat metabolic diseases. Despite its considerable potential, the regulatory mechanisms governing this activatio...
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| Format: | Article |
| Language: | English |
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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.202414073 |
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| author | Haojie Qin Yi Zhong Jinhui Huang Yanli Miao Meng Du Kai Huang |
| author_facet | Haojie Qin Yi Zhong Jinhui Huang Yanli Miao Meng Du Kai Huang |
| author_sort | Haojie Qin |
| collection | DOAJ |
| description | Abstract In mammals, the activation of thermogenic adipocytes, such as beige and brown adipocytes, can significantly increase overall energy expenditure, offering a promising strategy to combat metabolic diseases. Despite its considerable potential, the regulatory mechanisms governing this activation remain largely elusive. This study bridges this gap by elucidating that tripartite motif 56 (TRIM56), an E3 ubiquitin ligase, is upregulated in response to cold stimuli, thereby promoting the recruitment of beige adipocytes. Notably, the overexpression of TRIM56 in adipocytes is shown to help mice maintain a core temperature under cold conditions, as well as confer protection against diet‐induced obesity. Mechanistically, TRIM56 facilitates the degradation of the transducin‐like enhancer protein 3 (TLE3) protein by promoting its K48‐linked ubiquitination, which subsequently triggers the activation of thermogenic genes in subcutaneousl white adipose tissue and improved the metabolic profiles. These findings unveil a novel function for TRIM56 in adipocyte browning, suggesting its potential as a therapeutic target for the treatment of metabolic disorders. |
| format | Article |
| id | doaj-art-4d323a10ea474e76aa8af384d037972e |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-4d323a10ea474e76aa8af384d037972e2025-08-20T01:51:39ZengWileyAdvanced Science2198-38442025-04-011213n/an/a10.1002/advs.202414073TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3Haojie Qin0Yi Zhong1Jinhui Huang2Yanli Miao3Meng Du4Kai Huang5Clinic Center of Human Gene Research Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Rheumatology and Immunology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaClinic Center of Human Gene Research Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaDepartment of Cardiology The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052 ChinaClinic Center of Human Gene Research Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaClinic Center of Human Gene Research Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 ChinaAbstract In mammals, the activation of thermogenic adipocytes, such as beige and brown adipocytes, can significantly increase overall energy expenditure, offering a promising strategy to combat metabolic diseases. Despite its considerable potential, the regulatory mechanisms governing this activation remain largely elusive. This study bridges this gap by elucidating that tripartite motif 56 (TRIM56), an E3 ubiquitin ligase, is upregulated in response to cold stimuli, thereby promoting the recruitment of beige adipocytes. Notably, the overexpression of TRIM56 in adipocytes is shown to help mice maintain a core temperature under cold conditions, as well as confer protection against diet‐induced obesity. Mechanistically, TRIM56 facilitates the degradation of the transducin‐like enhancer protein 3 (TLE3) protein by promoting its K48‐linked ubiquitination, which subsequently triggers the activation of thermogenic genes in subcutaneousl white adipose tissue and improved the metabolic profiles. These findings unveil a novel function for TRIM56 in adipocyte browning, suggesting its potential as a therapeutic target for the treatment of metabolic disorders.https://doi.org/10.1002/advs.202414073adaptive thermogenesisLipolysisobesityubiquitin modificationsWhite adipose tissue browning |
| spellingShingle | Haojie Qin Yi Zhong Jinhui Huang Yanli Miao Meng Du Kai Huang TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3 Advanced Science adaptive thermogenesis Lipolysis obesity ubiquitin modifications White adipose tissue browning |
| title | TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3 |
| title_full | TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3 |
| title_fullStr | TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3 |
| title_full_unstemmed | TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3 |
| title_short | TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3 |
| title_sort | trim56 promotes white adipose tissue browning to attenuate obesity by degrading tle3 |
| topic | adaptive thermogenesis Lipolysis obesity ubiquitin modifications White adipose tissue browning |
| url | https://doi.org/10.1002/advs.202414073 |
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