{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:56:25Z","timestamp":1787165785591,"version":"build-2736575974"},"reference-count":68,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-136\/2025-03\/200007"],"award-info":[{"award-number":["451-03-136\/2025-03\/200007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Glucagon-like peptide-1 receptor agonists and lifestyle interventions effectively treat overt obesity, but the benefits\/risks of their combined early intervention during middle age remain unclear. This study investigated whether submaximal-dose liraglutide combined with strength\u2013endurance training improves metabolic and liver health, focusing on hepatic oxidative stress and lipid metabolism. Male Wistar rats (16 months old) received liraglutide (L; 0.186 mg\/kg\/day, s.c.), training (ladder climbing with weights, 3 times\/week), both (L+E) or saline for control middle-aged (C) and young adults (CY; 3\u20134 months old) for 7 weeks (n = 8\/group). Middle-aged rats exhibited age-related changes including higher body and visceral fat, increased hepatic and serum cholesterol, hepatic ALT and glutathione imbalance, and decreased soleus muscle (p &lt; 0.05, vs. CY). Exercise increased hepatic glycogen and oxidative stress markers and downregulated lipogenic genes, consistent with liver adaptation to training. L+E synergistically reduced body and visceral fat, hepatic and serum triglycerides, and the triglyceride\u2013glucose index, while reducing oxidative stress (p &lt; 0.05 vs. E, C) and lipogenic gene expression (p &lt; 0.05 vs. C), without affecting pancreas histopathology and function parameters, muscle mass or exercise load volume. In conclusion, submaximal liraglutide safely synergized with training to enhance metabolic health, improve hepatic redox balance and triglyceride metabolism in middle-aged rats, without mitigating cholesterol rise.<\/jats:p>","DOI":"10.3390\/antiox14121492","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T11:13:33Z","timestamp":1765538013000},"page":"1492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Synergistic Effect of Liraglutide and Strength\u2013Endurance Exercise Training on Hepatic Oxidative Stress and Lipid Metabolism in Middle-Aged Male Rats"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0249-2099","authenticated-orcid":false,"given":"Dragana","family":"Vlahovi\u0107","sequence":"first","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11108 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9141-5732","authenticated-orcid":false,"given":"Svetlana","family":"Trifunovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11108 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4895-9985","authenticated-orcid":false,"given":"Slavica","family":"Borkovi\u0107-Miti\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11108 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5651-7178","authenticated-orcid":false,"given":"Sla\u0111an","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11108 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6237-4021","authenticated-orcid":false,"given":"Ivona","family":"Gizdovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11108 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7941-8308","authenticated-orcid":false,"given":"Dieter","family":"L\u00fctjohann","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Venusberg\u2013Campus 1, 53127 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-763X","authenticated-orcid":false,"given":"Branko","family":"Filipovi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11108 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2664-3664","authenticated-orcid":false,"given":"Ljiljana","family":"Marina","sequence":"additional","affiliation":[{"name":"Center for Infertility and Endocrinology of Gender, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5496-0619","authenticated-orcid":false,"given":"Branka","family":"\u0160o\u0161i\u0107-Jurjevi\u0107","sequence":"additional","affiliation":[{"name":"Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11108 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101268","DOI":"10.1016\/j.arr.2021.101268","article-title":"Obesity and Aging: Molecular Mechanisms and Therapeutic Approaches","volume":"67","author":"Santos","year":"2021","journal-title":"Ageing Res. 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