{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T23:15:26Z","timestamp":1787786126848,"version":"build-2784847793"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T00:00:00Z","timestamp":1690502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minas Gerais Research Foundation\u2013FAPEMIG, research projects","award":["CDS APQ 02703\/18"],"award-info":[{"award-number":["CDS APQ 02703\/18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Insulin resistance is the link between obesity and type 2 diabetes mellitus. The molecular mechanism by which obese individuals develop insulin resistance has not yet been fully elucidated; however, inconclusive and contradictory studies have shown that oxidative stress may be involved in the process. Thus, this study aimed to evaluate the effect of reactive species on the mechanism of insulin resistance in diet-induced obese mice. Obese insulin-resistant mice were treated with N-acetylcysteine (NAC; 50 mg\/kg per day, for 15 days) by means of oral gavage. Twenty-four hours after the last NAC administration, the animals were euthanized and their tissues were extracted for biochemical and molecular analyses. NAC supplementation induced improved insulin resistance and fasting glycemia, without modifications in food intake, body weight, and adiposity. Obese mice showed increased dichlorofluorescein (DCF) oxidation, reduced catalase (CAT) activity, and reduced glutathione levels (GSH). However, treatment with NAC increased GSH and CAT activity and reduced DCF oxidation. The gastrocnemius muscle of obese mice showed an increase in nuclear factor kappa B (NF\u03baB) and protein tyrosine phosphatase (PTP1B) levels, as well as c-Jun N-terminal kinase (JNK) phosphorylation compared to the control group; however, NAC treatment reversed these changes. Considering the molecules involved in insulin signaling, there was a reduction in insulin receptor substrate (IRS) and protein kinase B (Akt) phosphorylation. However, NAC administration increased IRS and Akt phosphorylation and IRS\/PI3k (phosphoinositide 3-kinase) association. The results demonstrated that oxidative stress-associated obesity could be a mechanism involved in insulin resistance, at least in this animal model.<\/jats:p>","DOI":"10.3390\/ijms241512088","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T07:35:24Z","timestamp":1690529724000},"page":"12088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Role of Oxidative Stress on Insulin Resistance in Diet-Induced Obesity Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Bruno Luiz da Silva","family":"Pieri","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Crici\u00fama 88806-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7794-6588","authenticated-orcid":false,"given":"Matheus Scarpatto","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Crici\u00fama 88806-000, Brazil"},{"name":"Graduate Program in Biological Sciences: Biochemistry, Universidade Federal Do Rio Grande Do Sul, Porto Alegre 90010-150, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemelin Resende","family":"Farias","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Crici\u00fama 88806-000, Brazil"},{"name":"Graduate Program in Biological Sciences: Biochemistry, Universidade Federal Do Rio Grande Do Sul, Porto Alegre 90010-150, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo de Bem","family":"Silveira","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Crici\u00fama 88806-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vict\u00f3ria de Souza Gomes da Cunha","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health, Department of Internal Medicine, Medicine School, Federal University of Juiz de Fora, Juiz de Fora 36038-330, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo Cesar Lock","family":"Silveira","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Pathophysiology, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Crici\u00fama 88806-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4904-5675","authenticated-orcid":false,"given":"Claudio Teodoro","family":"De Souza","sequence":"additional","affiliation":[{"name":"Post Graduate Program in Health, Department of Internal Medicine, Medicine School, Federal University of Juiz de Fora, Juiz de Fora 36038-330, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2013.00093","article-title":"Recent advances in obesity-induced inflammation and insulin resistance","volume":"4","author":"Tateya","year":"2013","journal-title":"Front. 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