Wei Chen, Youhua Liu, Jiaqi Liu, Yushi Chen, Xinxia Wang
{"title":"Acute exercise promotes WAT browning by remodeling mRNA m<sup>6</sup>A methylation.","authors":"Wei Chen, Youhua Liu, Jiaqi Liu, Yushi Chen, Xinxia Wang","doi":"10.1016/j.lfs.2024.123269","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Regular exercise promotes the beiging and metabolic adaptations of white adipose tissue (WAT) through the cumulative transcriptional responses that occur after each exercise session. However, the effects of a single bout of acute exercise and the role of N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) in these adaptations remain unclear. We aim to investigate this further.</p><p><strong>Materials and methods: </strong>We constructed mouse models for chronic (8 weeks of running) and acute (single 1-hour run) exercise to study the effects on white adipose tissue (WAT) metabolism and beiging through metabolic phenotyping and transcriptome sequencing. Additionally, we explored the impact of acute exercise on WAT m<sup>6</sup>A modification and target genes, combining m<sup>6</sup>A regulators with cell models to elucidate the role of m<sup>6</sup>A in WAT exercise adaptation.</p><p><strong>Key findings: </strong>Here, we reveal that upregulated m<sup>6</sup>A modification after acute exercise induces the formation of glycolytic beige fat (g-beige fat) in WAT. Mechanistically, the metabolite β-hydroxybutyrate (BHBA) secreted after acute exercise upregulates m<sup>6</sup>A modification in WAT. This enhances m<sup>6</sup>A-dependent translation of the histone acetyltransferase CREBBP, promoting the transcription of key beiging genes by increasing chromatin accessibility. Pharmacologically elevating circulating BHBA mimics the metabolic response induced by acute exercise, upregulating m<sup>6</sup>A modification and its downstream signals. Additionally, BHBA exhibits long-term effects, improving metabolic homeostasis in obesity by promoting thermogenesis in WAT.</p><p><strong>Significance: </strong>Our results reveal the role of metabolites in WAT metabolic adaptation through m<sup>6</sup>A-mediated chromatin accessibility after acute exercise, providing a novel therapeutic target for regulating WAT metabolism from a nutritional epigenetics perspective.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123269"},"PeriodicalIF":5.2000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.lfs.2024.123269","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Aims: Regular exercise promotes the beiging and metabolic adaptations of white adipose tissue (WAT) through the cumulative transcriptional responses that occur after each exercise session. However, the effects of a single bout of acute exercise and the role of N6-methyladenosine (m6A) in these adaptations remain unclear. We aim to investigate this further.
Materials and methods: We constructed mouse models for chronic (8 weeks of running) and acute (single 1-hour run) exercise to study the effects on white adipose tissue (WAT) metabolism and beiging through metabolic phenotyping and transcriptome sequencing. Additionally, we explored the impact of acute exercise on WAT m6A modification and target genes, combining m6A regulators with cell models to elucidate the role of m6A in WAT exercise adaptation.
Key findings: Here, we reveal that upregulated m6A modification after acute exercise induces the formation of glycolytic beige fat (g-beige fat) in WAT. Mechanistically, the metabolite β-hydroxybutyrate (BHBA) secreted after acute exercise upregulates m6A modification in WAT. This enhances m6A-dependent translation of the histone acetyltransferase CREBBP, promoting the transcription of key beiging genes by increasing chromatin accessibility. Pharmacologically elevating circulating BHBA mimics the metabolic response induced by acute exercise, upregulating m6A modification and its downstream signals. Additionally, BHBA exhibits long-term effects, improving metabolic homeostasis in obesity by promoting thermogenesis in WAT.
Significance: Our results reveal the role of metabolites in WAT metabolic adaptation through m6A-mediated chromatin accessibility after acute exercise, providing a novel therapeutic target for regulating WAT metabolism from a nutritional epigenetics perspective.
期刊介绍：
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
