{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T04:47:24Z","timestamp":1782535644330,"version":"3.54.5"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100017700","name":"Henan Provincial Science and Technology Research Project","doi-asserted-by":"crossref","award":["262102310228"],"award-info":[{"award-number":["262102310228"]}],"id":[{"id":"10.13039\/501100017700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Exercise is one of the safe and effective methods to improve obesity and its complications, but the mechanism has not been fully elucidated. Sestrin2 (SESN2) is a stress-induced protein that protects cells from stress damage. The role and mechanism of SESN2 in the improvement of obesity-induced cardiac dysfunction by exercise are still unclear. Male C57BL\/6J mice were used to prepare a high-fat diet-induced obesity mouse model and conducted aerobic exercise training. After training, echocardiography was used to evaluate the cardiac function of mice, and HE and Masson staining were used to assess the extent of cardiac damage. Cell experiments were conducted using the H9C2 cell line derived from embryonic rat hearts, with the intervention of palmitic acid ester and exogenous SESN2. We detected indicators related to myocardial cell damage, fibrosis, inflammation, and oxidative stress, as well as the activation level of the AMPK-PGC-1\u03b1 signaling pathway. The results showed that aerobic exercise significantly inhibited myocardial fibrosis, inflammation, oxidative stress, and cell damage in HFD mice, upregulated cardiac SESN2 expression, and activated the AMPK-PGC-1\u03b1 signaling pathway. Cell experiments have found that exogenous SESN2 pretreatment alleviates palmitate-induced injury, inflammation, and oxidative stress in H9C2 cardiomyocytes, and activates the AMPK-PGC-1\u03b1 signaling pathway. This indicates that aerobic exercise significantly upregulates the expression of SESN2 and activates the AMPK-PGC-1\u03b1 signaling pathway, which is potentially involved in alleviating myocardial inflammation, oxidative stress, cardiac fibrosis and cardiac dysfunction in HFD mice.<\/jats:p>","DOI":"10.3390\/ijms27135670","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic Role of Sestrin2 in Exercise-Mediated Cardioprotection Against Obesity-Related Cardiomyopathy"],"prefix":"10.3390","volume":"27","author":[{"given":"Meili","family":"Hao","sequence":"first","affiliation":[{"name":"School of Physical Education, Luoyang Normal University, Luoyang 471934, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9108-2691","authenticated-orcid":false,"given":"Wanyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Physical Education, Shaanxi Normal University, Xi\u2019an 710119, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Physical Education, Luoyang Normal University, Luoyang 471934, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8594-8978","authenticated-orcid":false,"given":"Wenyan","family":"Bo","sequence":"additional","affiliation":[{"name":"School of Physical Education, Shanxi University, Taiyuan 030006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1016\/S0140-6736(25)01637-X","article-title":"Burden of 375 diseases and injuries, risk-attributable burden of 88 risk factors, and healthy life expectancy in 204 countries and territories, including 660 subnational locations, 1990\u20132023: A systematic analysis for the Global Burden of Disease Study 2023","volume":"406","author":"Hay","year":"2025","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dong, Y., and Yang, B. 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