{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T19:13:34Z","timestamp":1785870814852,"version":"3.56.0"},"reference-count":30,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"unspecified","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Xijing Hospital Disciplines Boosting Project","award":["XJZT25CX11"],"award-info":[{"award-number":["XJZT25CX11"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82300703"],"award-info":[{"award-number":["82300703"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["egastro"],"accepted":{"date-parts":[[2026,1,22]]},"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>MicroRNAs critically regulate metabolic dysfunction-associated steatotic liver disease (MASLD) progression and intervention. Lifestyle modifications, particularly exercise and time-restricted feeding (TRF), emerge as effective non-pharmacological strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MiR-802 expression was quantified in plasma exosomes and hepatic tissues of MASLD mouse models using quantitative PCR and sequencing. In vivo and in vitro gain-of-function and loss-of-function experiments assessed its regulatory effects on hepatic lipotoxicity, complemented by bioinformatic predictions and luciferase-based validation of upstream transcription factors and downstream targets. Functional crosstalk between miR-802 and its regulatory network was examined under lipotoxic conditions. Therapeutic interventions, including exercise and TRF, were implemented in high-fat diet fed mice, with subsequent evaluation of miR-802 expression dynamics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we show elevated miR-802 levels in plasma exosomes and livers of MASLD mice, with its inhibition reducing hepatocyte lipotoxicity. Mechanistically, peroxisome proliferator-activated receptor gamma (PPAR\u03b3) promotes miR-802 transcription, whereas miR-802 suppresses the proteasome 26S subunit ubiquitin receptor, non-ATPase 2 (Psmd2). Genetic and pharmacological modulation of PPAR\u03b3 downregulates miR-802 and ameliorates MASLD. Notably, both exercise and TRF reduce hepatic PPAR\u03b3 and miR-802 expression and improve MASLD via the PPAR\u03b3-miR-802-Psmd2 axis, revealing lifestyle modification-mediated epigenetic regulation in MASLD pathophysiology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study reveals the PPAR\u03b3-miR-802-Psmd2 axis as a central regulatory mechanism in MASLD pathogenesis and innovatively links lifestyle interventions (exercise and TRF) to therapeutic effects via this pathway.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/egastro-2025-100334","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T05:05:23Z","timestamp":1772082323000},"page":"e100334","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Exercise and dietary interventions ameliorate MASLD via the hepatic PPAR\u03b3-miR-802-Psmd2 axis"],"prefix":"10.1136","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0668-4658","authenticated-orcid":false,"given":"Yingying","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhensheng","family":"Yue","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juanli","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"He","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi\u2019an, Shaanxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"2026022521051253000_4.1.e100334.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.015"},{"key":"2026022521051253000_4.1.e100334.2","doi-asserted-by":"crossref","DOI":"10.1136\/egastro-2025-100218","article-title":"Steatotic liver disease and cancer: from pathogenesis to therapeutic targets","volume":"3","author":"Yang","year":"2025","journal-title":"eGastroenterology"},{"key":"2026022521051253000_4.1.e100334.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.03.040"},{"key":"2026022521051253000_4.1.e100334.4","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.11.039"},{"key":"2026022521051253000_4.1.e100334.5","doi-asserted-by":"publisher","DOI":"10.1038\/nature11793"},{"key":"2026022521051253000_4.1.e100334.6","doi-asserted-by":"crossref","unstructured":"Zhang F , Ma D , Zhao W , et al . 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