{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T15:05:13Z","timestamp":1784387113114,"version":"3.55.0"},"reference-count":37,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,5,1]]},"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) can progress to fibrosis and hepatocellular carcinoma, with TGF-\u03b2 playing a key role. UBAP2L regulates TGF-\u03b2 expression, but its role in NAFLD remains unclear. While exercise improves NAFLD and cold exposure enhances lipid metabolism, their combined effects on NAFLD-induced fibrosis are unknown. This study examines whether exercise with cold exposure attenuates NAFLD-induced fibrosis via the UBAP2L-mediated TGF-\u03b2\/SMAD2\/3 pathway. Fifty 5-week-old male C57BL\/6N mice were assigned to five groups: normal control (C), high-fat diet (H), high-fat diet with cold exposure (HC), high-fat diet with exercise (HE), and high-fat diet with exercise and cold exposure (HCE). After 8 weeks of a high-fat diet, the HE and HCE groups underwent treadmill exercise (50 min\/session, 5 days\/week for 8 weeks). H&amp;E, Oil Red O, Masson staining, biochemical analyses, proteomics, Western blot and RT-qPCR were used to assess fibrosis-related markers. We found that body weight, liver weight, hepatic TG, TC, LDL, Glu, CHO, AST and ALT were significantly elevated in the H group. In the HCE group, hepatic TG and BUN decreased, while HDL increased. Proteomics identified UBAP2L as the most upregulated protein in the H group, but it was downregulated in the HCE group. Western blot confirmed UBAP2L overexpression in the H group and its reduction in the HCE group, with decreased \u03b1-SMA. RT-qPCR showed elevated Tgf-\u03b2, \u03b1-Sma, Smad2, Smad3, Col1a2 and Ubap2l in the H group, which were downregulated by exercise with cold exposure. Exercise with cold exposure can reduce NAFLD-induced hepatic fibrosis, probably by downregulating UBAP2L and suppressing the TGF-\u03b2\/SMAD2 pathway. These suggest exercise with cold exposure may be more effective than exercise at normal temperatures in mitigating NAFLD-related fibrosis.<\/jats:p>","DOI":"10.1530\/joe-24-0351","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T14:47:51Z","timestamp":1743432471000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":4,"title":["Cold aerobic exercise mitigates NAFLD fibrosis through UBAP2L-regulated TGF-\u03b2\/SMAD2 signaling"],"prefix":"10.1530","volume":"265","author":[{"given":"Jianhong","family":"Zhang","sequence":"first","affiliation":[{"name":"Sport Science School, Beijing Sport University 1 , ,","place":["Beijing, China"]},{"name":"Sports Medical Supervision Center, National Institute of Sports Medicine 2 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0178-2183","authenticated-orcid":true,"given":"Chaoyang","family":"Li","sequence":"additional","affiliation":[{"name":"Sport Science School, Beijing Sport University 1 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Rao","sequence":"additional","affiliation":[{"name":"Exercise Biology Research Center, China Institute of Sport Science 3 , ,","place":["Beijing, China"]},{"name":"College of Physical Education, Shanghai Normal University 4 , ,","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Geng","sequence":"additional","affiliation":[{"name":"Sport Science School, Beijing Sport University 1 , ,","place":["Beijing, China"]},{"name":"Exercise Biology Research Center, China Institute of Sport Science 3 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Liang","sequence":"additional","affiliation":[{"name":"Sports Medical Supervision Center, National Institute of Sports Medicine 2 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Liu","sequence":"additional","affiliation":[{"name":"Exercise Biology Research Center, China Institute of Sport Science 3 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Huang","sequence":"additional","affiliation":[{"name":"Exercise Biology Research Center, China Institute of Sport Science 3 , ,","place":["Beijing, China"]},{"name":"School of Kinesiology, Shanghai University of Sport 5 , ,","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongzhe","family":"Wu","sequence":"additional","affiliation":[{"name":"Sport Science School, Beijing Sport University 1 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Kinesiology, Shanghai University of Sport 5 , ,","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiexiu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Exercise Biology Research Center, China Institute of Sport Science 3 , ,","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"2026070806134373100_bib1","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/s41575-020-00406-0","article-title":"Nonalcoholic fatty liver disease: another leap forward","volume":"18","author":"Abdelmalek","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2026070806134373100_bib2","doi-asserted-by":"crossref","DOI":"10.1016\/j.yexmp.2021.104733","article-title":"TGF-\u03b21 signaling can worsen NAFLD with liver fibrosis backdrop","volume":"124","author":"Ahmed","year":"2022","journal-title":"Exp Mol Pathol"},{"key":"2026070806134373100_bib3","doi-asserted-by":"crossref","first-page":"5012","DOI":"10.1096\/fj.201601219RRR","article-title":"UBAP2L is amplified in a large subset of human lung adenocarcinoma and is critical for epithelial lung cell identity and tumor metastasis","volume":"31","author":"Aucagne","year":"2017","journal-title":"FASEB J"},{"key":"2026070806134373100_bib4","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1139\/y89-062","article-title":"Energy balance and diabetes. 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