Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming
Abstract The liver-adipose axis represents a crucial regulatory network that governs systemic lipid homeostasis, with signals originating from the liver orchestrating the plasticity of adipose tissue through diverse mechanisms. A comprehensive understanding of these bidirectional communication pathw...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-08-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-025-02697-1 |
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| _version_ | 1849226640257712128 |
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| author | Xiujuan Gao Junqing Xu Zengqiang Xu Mengxin Jiang Jiahao Zhu Yang Geng Shengjun Dong Yanuo Li Zhengtong Zhou Yingjiang Xu |
| author_facet | Xiujuan Gao Junqing Xu Zengqiang Xu Mengxin Jiang Jiahao Zhu Yang Geng Shengjun Dong Yanuo Li Zhengtong Zhou Yingjiang Xu |
| author_sort | Xiujuan Gao |
| collection | DOAJ |
| description | Abstract The liver-adipose axis represents a crucial regulatory network that governs systemic lipid homeostasis, with signals originating from the liver orchestrating the plasticity of adipose tissue through diverse mechanisms. A comprehensive understanding of these bidirectional communication pathways may uncover novel therapeutic approaches for metabolic disorders. Our research demonstrates that exposure to cold stimulates the liver to secrete exosomes, which enhance thermogenic activation in adipose tissue, as observed in both in vitro and in vivo models. This enhancement of thermogenesis is mechanistically associated with the cold-induced upregulation of hepatocyte-derived exosomal miR-293-5p. Importantly, the pharmacological administration of a miR-293-5p agomir significantly mitigates diet-induced obesity and related metabolic dysfunctions in murine models. Through mechanistic analysis, we identified Tet1 as a direct downstream target of miR-293-5p, noting that the ectopic expression of Tet1 disrupts the thermogenic programming of brown adipose tissue (BAT) independently of miR-293-5p modulation. Our findings establish cold-activated hepatocyte exosomes as endocrine signaling mediators that carry thermogenic microRNA cargos, with miR-293-5p emerging as a key regulator. |
| format | Article |
| id | doaj-art-4aa8e3cfad294197bfd6ed1327ed02e5 |
| institution | Kabale University |
| issn | 2058-7716 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj-art-4aa8e3cfad294197bfd6ed1327ed02e52025-08-24T11:08:23ZengNature Publishing GroupCell Death Discovery2058-77162025-08-0111111710.1038/s41420-025-02697-1Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogrammingXiujuan Gao0Junqing Xu1Zengqiang Xu2Mengxin Jiang3Jiahao Zhu4Yang Geng5Shengjun Dong6Yanuo Li7Zhengtong Zhou8Yingjiang Xu9Binzhou Medical University HospitalBinzhou Medical University HospitalBinzhou Medical University HospitalBinzhou Medical University HospitalBinzhou Medical University HospitalBinzhou Medical University HospitalBinzhou Medical University HospitalDepartment of Pathophysiology, School of Basic Medicine, Binzhou Medical UniversityInstitute of Medical Genomics, Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical SciencesBinzhou Medical University HospitalAbstract The liver-adipose axis represents a crucial regulatory network that governs systemic lipid homeostasis, with signals originating from the liver orchestrating the plasticity of adipose tissue through diverse mechanisms. A comprehensive understanding of these bidirectional communication pathways may uncover novel therapeutic approaches for metabolic disorders. Our research demonstrates that exposure to cold stimulates the liver to secrete exosomes, which enhance thermogenic activation in adipose tissue, as observed in both in vitro and in vivo models. This enhancement of thermogenesis is mechanistically associated with the cold-induced upregulation of hepatocyte-derived exosomal miR-293-5p. Importantly, the pharmacological administration of a miR-293-5p agomir significantly mitigates diet-induced obesity and related metabolic dysfunctions in murine models. Through mechanistic analysis, we identified Tet1 as a direct downstream target of miR-293-5p, noting that the ectopic expression of Tet1 disrupts the thermogenic programming of brown adipose tissue (BAT) independently of miR-293-5p modulation. Our findings establish cold-activated hepatocyte exosomes as endocrine signaling mediators that carry thermogenic microRNA cargos, with miR-293-5p emerging as a key regulator.https://doi.org/10.1038/s41420-025-02697-1 |
| spellingShingle | Xiujuan Gao Junqing Xu Zengqiang Xu Mengxin Jiang Jiahao Zhu Yang Geng Shengjun Dong Yanuo Li Zhengtong Zhou Yingjiang Xu Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming Cell Death Discovery |
| title | Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming |
| title_full | Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming |
| title_fullStr | Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming |
| title_full_unstemmed | Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming |
| title_short | Cold-induced hepatocyte-derived exosomes activate brown adipose thermogenesis via miR-293-5p-mediated transcriptional reprogramming |
| title_sort | cold induced hepatocyte derived exosomes activate brown adipose thermogenesis via mir 293 5p mediated transcriptional reprogramming |
| url | https://doi.org/10.1038/s41420-025-02697-1 |
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