Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis

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 and Liang Guo ()
Additional contact information
Jie-Ying Zhu: Shanghai University of Sport
Min Chen: Shanghai University of Sport
Wang-Jing Mu: Shanghai University of Sport
Hong-Yang Luo: Shanghai University of Sport
Yang Li: Shanghai University of Sport
Shan Li: Shanghai University of Sport
Lin-Jing Yan: Shanghai University of Sport
Ruo-Ying Li: Shanghai University of Sport
Meng-Ting Yin: Shanghai University of Sport
Xin Li: Shanghai University of Sport
Hu-Min Chen: Shanghai University of Sport
Liang Guo: Shanghai University of Sport

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-58467-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-58467-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-58467-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().