Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT
Abstract Characterized by UCP1 expression and abundant mitochondria, brown adipose tissue (BAT) plays a crucial role in energy balance by converting chemical energy into heat through the cost of ATP production. In this study, it was demonstrated that Trib3 is a critical determinant of BAT-mediated e...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2024-12-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-024-01361-5 |
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| author | Hyejin Yeo Ji-Hye Lim Ji Eom MinJeong Kim Hyeji Kwon Sang-Wook Kang Youngsup Song |
| author_facet | Hyejin Yeo Ji-Hye Lim Ji Eom MinJeong Kim Hyeji Kwon Sang-Wook Kang Youngsup Song |
| author_sort | Hyejin Yeo |
| collection | DOAJ |
| description | Abstract Characterized by UCP1 expression and abundant mitochondria, brown adipose tissue (BAT) plays a crucial role in energy balance by converting chemical energy into heat through the cost of ATP production. In this study, it was demonstrated that Trib3 is a critical determinant of BAT-mediated energy expenditure and whole-body energy homeostasis. Under 60% high-fat diet conditions, Trib3 expression in BAT was elevated. Mice deficient in Trib3 are resistant to diet-induced obesity and exhibit improved glucose homeostasis due to enhanced BAT activity. Furthermore, brown adipocyte progenitor cells (APCs) lacking Trib3 exhibited increased proliferation and promoted brown adipocyte differentiation and mitochondrial biogenesis, contributing to the increase in the maximal thermogenic capacity of BAT in Trib3-deficient mice. Mechanistically, it was discovered that Trib3 expression is upregulated by free fatty acids at the transcriptional level and synergistically upregulated by DAG-PKC at the posttranslational level. This occurs through the modulation of COP1-mediated Trib3 protein turnover. Interestingly, the level of Trib3 expression in BAT increased with age. Trib3 knockout mice were protected from aging-related weight gain and impaired glucose homeostasis. These results suggest that Trib3 acts as an obesity- and aging-associated factor that negatively regulates BAT activity and that the loss of Trib3 may provide a beneficial approach to prevent obesity and aging-associated metabolic syndrome by increasing the thermogenic capacity of BAT. |
| format | Article |
| id | doaj-art-8fd9b3220a2d4274b89065ac434b5e8f |
| institution | Kabale University |
| issn | 2092-6413 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj-art-8fd9b3220a2d4274b89065ac434b5e8f2024-12-29T12:11:12ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132024-12-0156122690270210.1038/s12276-024-01361-5Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BATHyejin Yeo0Ji-Hye Lim1Ji Eom2MinJeong Kim3Hyeji Kwon4Sang-Wook Kang5Youngsup Song6Department of Brain Science, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of MedicineDepartment of Brain Science, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of MedicineDepartment of Brain Science, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of MedicineDepartment of Brain Science, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of MedicineDepartment of Brain Science, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of MedicineDepartment of Biochemistry and Molecular Biology, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of MedicineDepartment of Brain Science, Brain Korea 21 Project, Asan Medical Center, University of Ulsan College of MedicineAbstract Characterized by UCP1 expression and abundant mitochondria, brown adipose tissue (BAT) plays a crucial role in energy balance by converting chemical energy into heat through the cost of ATP production. In this study, it was demonstrated that Trib3 is a critical determinant of BAT-mediated energy expenditure and whole-body energy homeostasis. Under 60% high-fat diet conditions, Trib3 expression in BAT was elevated. Mice deficient in Trib3 are resistant to diet-induced obesity and exhibit improved glucose homeostasis due to enhanced BAT activity. Furthermore, brown adipocyte progenitor cells (APCs) lacking Trib3 exhibited increased proliferation and promoted brown adipocyte differentiation and mitochondrial biogenesis, contributing to the increase in the maximal thermogenic capacity of BAT in Trib3-deficient mice. Mechanistically, it was discovered that Trib3 expression is upregulated by free fatty acids at the transcriptional level and synergistically upregulated by DAG-PKC at the posttranslational level. This occurs through the modulation of COP1-mediated Trib3 protein turnover. Interestingly, the level of Trib3 expression in BAT increased with age. Trib3 knockout mice were protected from aging-related weight gain and impaired glucose homeostasis. These results suggest that Trib3 acts as an obesity- and aging-associated factor that negatively regulates BAT activity and that the loss of Trib3 may provide a beneficial approach to prevent obesity and aging-associated metabolic syndrome by increasing the thermogenic capacity of BAT.https://doi.org/10.1038/s12276-024-01361-5 |
| spellingShingle | Hyejin Yeo Ji-Hye Lim Ji Eom MinJeong Kim Hyeji Kwon Sang-Wook Kang Youngsup Song Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT Experimental and Molecular Medicine |
| title | Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT |
| title_full | Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT |
| title_fullStr | Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT |
| title_full_unstemmed | Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT |
| title_short | Diet-induced obesity and aging-induced upregulation of Trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of BAT |
| title_sort | diet induced obesity and aging induced upregulation of trib3 interfere with energy homeostasis by downregulating the thermogenic capacity of bat |
| url | https://doi.org/10.1038/s12276-024-01361-5 |
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