Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis
Abstract Exercise combats obesity and metabolic disorders, but the underlying mechanism is incompletely understood. KLF10, a transcription factor involved in various biological processes, has an undefined role in adipose tissue and obesity. Here, we show that exercise facilitates adipocyte-derived K...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58467-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850265845619490816 |
|---|---|
| author | Jie-Ying Zhu Min Chen Wang-Jing Mu Hong-Yang Luo Yang Li Shan Li Lin-Jing Yan Ruo-Ying Li Meng-Ting Yin Xin Li Hu-Min Chen Liang Guo |
| author_facet | Jie-Ying Zhu Min Chen Wang-Jing Mu Hong-Yang Luo Yang Li Shan Li Lin-Jing Yan Ruo-Ying Li Meng-Ting Yin Xin Li Hu-Min Chen Liang Guo |
| author_sort | Jie-Ying Zhu |
| collection | DOAJ |
| description | Abstract Exercise combats obesity and metabolic disorders, but the underlying mechanism is incompletely understood. KLF10, a transcription factor involved in various biological processes, has an undefined role in adipose tissue and obesity. Here, we show that exercise facilitates adipocyte-derived KLF10 expression via SIRT1/FOXO1 pathway. Adipocyte-specific knockout of KLF10 blunts exercise-promoted white adipose browning, energy expenditure, fat loss, glucose tolerance in diet-induced obese male mice. Conversely, adipocyte-specific transgenic expression of KLF10 in male mice enhanced the above metabolic profits induced by exercise. Mechanistically, KLF10 interacts with FOXO1 and facilitates the recruitment of KDM4A to form a ternary complex on the promoter regions of Pnpla2 and Lipe genes to promote these key lipolytic genes expression by demethylating H3K9me3 on their promoters, which facilitates lipolysis to defend against obesity in male mice. As a downstream effector responding to exercise, adipose KLF10 could act as a potential target in the fight against obesity. |
| format | Article |
| id | doaj-art-1d8d0d3622a04304b4739e54f9a41b13 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1d8d0d3622a04304b4739e54f9a41b132025-08-20T01:54:19ZengNature PortfolioNature Communications2041-17232025-04-0116112010.1038/s41467-025-58467-1Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysisJie-Ying Zhu0Min Chen1Wang-Jing Mu2Hong-Yang Luo3Yang Li4Shan Li5Lin-Jing Yan6Ruo-Ying Li7Meng-Ting Yin8Xin Li9Hu-Min Chen10Liang Guo11School of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportSchool of Exercise and Health and Collaborative Innovation Center for Sports and Public Health, Shanghai University of SportAbstract Exercise combats obesity and metabolic disorders, but the underlying mechanism is incompletely understood. KLF10, a transcription factor involved in various biological processes, has an undefined role in adipose tissue and obesity. Here, we show that exercise facilitates adipocyte-derived KLF10 expression via SIRT1/FOXO1 pathway. Adipocyte-specific knockout of KLF10 blunts exercise-promoted white adipose browning, energy expenditure, fat loss, glucose tolerance in diet-induced obese male mice. Conversely, adipocyte-specific transgenic expression of KLF10 in male mice enhanced the above metabolic profits induced by exercise. Mechanistically, KLF10 interacts with FOXO1 and facilitates the recruitment of KDM4A to form a ternary complex on the promoter regions of Pnpla2 and Lipe genes to promote these key lipolytic genes expression by demethylating H3K9me3 on their promoters, which facilitates lipolysis to defend against obesity in male mice. As a downstream effector responding to exercise, adipose KLF10 could act as a potential target in the fight against obesity.https://doi.org/10.1038/s41467-025-58467-1 |
| spellingShingle | Jie-Ying Zhu Min Chen Wang-Jing Mu Hong-Yang Luo Yang Li Shan Li Lin-Jing Yan Ruo-Ying Li Meng-Ting Yin Xin Li Hu-Min Chen Liang Guo Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis Nature Communications |
| title | Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis |
| title_full | Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis |
| title_fullStr | Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis |
| title_full_unstemmed | Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis |
| title_short | Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis |
| title_sort | exercise induced anti obesity effects in male mice generated by a foxo1 klf10 reinforcing loop promoting adipose lipolysis |
| url | https://doi.org/10.1038/s41467-025-58467-1 |
| work_keys_str_mv | AT jieyingzhu exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT minchen exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT wangjingmu exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT hongyangluo exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT yangli exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT shanli exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT linjingyan exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT ruoyingli exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT mengtingyin exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT xinli exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT huminchen exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis AT liangguo exerciseinducedantiobesityeffectsinmalemicegeneratedbyafoxo1klf10reinforcinglooppromotingadiposelipolysis |