Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3
Abstract Background Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potent...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-022-01287-2 |
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| author | Chunling Xue Xuechun Li Li Ba Yamei Shen Zhao Sun Junjie Gu Ying Yang Qin Han Robert Chunhua Zhao |
| author_facet | Chunling Xue Xuechun Li Li Ba Yamei Shen Zhao Sun Junjie Gu Ying Yang Qin Han Robert Chunhua Zhao |
| author_sort | Chunling Xue |
| collection | DOAJ |
| description | Abstract Background Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potential targets for therapeutic approaches in metabolic disorders, including obesity. All adipocytes, including beige adipocytes, differentiate from mesenchymal stem cells (MSCs), which may provide an important path for clinical intervention; however, the mechanism of beiging of human adipose cell-derived MSCs is not fully understood. Here, we provide insights on the role of IRISIN, which is known to be secreted by skeletal muscle and promote beiging of white fat. Results We established an IRISIN-induced mesenchymal stem cell beiging model and found that IRISIN protein interacts with the MSC membrane protein TRPC3. This interaction results in calcium influx and consequential activation of Erk and Akt signaling pathways, which causes phosphorylation of PPARγ. The phosphorylated PPARγ enters the nucleus and binds the UCP1 promoter region. Furthermore, the role of TRPC3 in the beiging of MSCs was largely abolished in Trpc3−/− mice. We additionally demonstrate that the calcium concentration in the brain of mice increases upon IRISIN stimulation, followed by an increase in the content of excitatory amino acids and norepinephrine, while Trpc3−/− mice exhibit the reverse effect. Conclusions We found that TRPC3 is a key factor in irisin-induced beiging of MSCs, which may provide a new target pathway in addressing metabolic disorders. Our results additionally suggest that the interaction of irisin with TRPC3 may affect multiple tissues, including the brain. Graphical abstract |
| first_indexed | 2024-04-13T08:14:35Z |
| format | Article |
| id | doaj.art-4cacc3b0f5cd4f4e8396c87a3f90f44c |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-13T08:14:35Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-4cacc3b0f5cd4f4e8396c87a3f90f44c2022-12-22T02:54:50ZengBMCBMC Biology1741-70072022-05-0120112010.1186/s12915-022-01287-2Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3Chunling Xue0Xuechun Li1Li Ba2Yamei Shen3Zhao Sun4Junjie Gu5Ying Yang6Qin Han7Robert Chunhua Zhao8Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No.BZO381)Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No.BZO381)Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No.BZO381)Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No.BZO381)Department of oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeDepartment of oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeDepartment of oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical CollegeInstitute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No.BZO381)Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College Hospital, Center of Excellence in Tissue Engineering Chinese Academy of Medical Sciences, Beijing Key Laboratory (No.BZO381)Abstract Background Beiging of white fat plays an important role in energy metabolism. Beige adipocytes contribute to the regulation of body weight and body temperature through expenditure of chemical energy to produce heat, and they have therefore recently attracted considerable attention as potential targets for therapeutic approaches in metabolic disorders, including obesity. All adipocytes, including beige adipocytes, differentiate from mesenchymal stem cells (MSCs), which may provide an important path for clinical intervention; however, the mechanism of beiging of human adipose cell-derived MSCs is not fully understood. Here, we provide insights on the role of IRISIN, which is known to be secreted by skeletal muscle and promote beiging of white fat. Results We established an IRISIN-induced mesenchymal stem cell beiging model and found that IRISIN protein interacts with the MSC membrane protein TRPC3. This interaction results in calcium influx and consequential activation of Erk and Akt signaling pathways, which causes phosphorylation of PPARγ. The phosphorylated PPARγ enters the nucleus and binds the UCP1 promoter region. Furthermore, the role of TRPC3 in the beiging of MSCs was largely abolished in Trpc3−/− mice. We additionally demonstrate that the calcium concentration in the brain of mice increases upon IRISIN stimulation, followed by an increase in the content of excitatory amino acids and norepinephrine, while Trpc3−/− mice exhibit the reverse effect. Conclusions We found that TRPC3 is a key factor in irisin-induced beiging of MSCs, which may provide a new target pathway in addressing metabolic disorders. Our results additionally suggest that the interaction of irisin with TRPC3 may affect multiple tissues, including the brain. Graphical abstracthttps://doi.org/10.1186/s12915-022-01287-2Mesenchymal stem cellsBeigingIRISINTRPC3Calcium influxEnergy metabolism |
| spellingShingle | Chunling Xue Xuechun Li Li Ba Yamei Shen Zhao Sun Junjie Gu Ying Yang Qin Han Robert Chunhua Zhao Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3 BMC Biology Mesenchymal stem cells Beiging IRISIN TRPC3 Calcium influx Energy metabolism |
| title | Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3 |
| title_full | Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3 |
| title_fullStr | Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3 |
| title_full_unstemmed | Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3 |
| title_short | Irisin mediates beiging of adipose-derived mesenchymal stem cells through binding to TRPC3 |
| title_sort | irisin mediates beiging of adipose derived mesenchymal stem cells through binding to trpc3 |
| topic | Mesenchymal stem cells Beiging IRISIN TRPC3 Calcium influx Energy metabolism |
| url | https://doi.org/10.1186/s12915-022-01287-2 |
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