{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T16:41:54Z","timestamp":1767890514118,"version":"3.49.0"},"reference-count":60,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T00:00:00Z","timestamp":1679875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de Nivel Superior","award":["88882.346533\/2019-01"],"award-info":[{"award-number":["88882.346533\/2019-01"]}]},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de Nivel Superior","award":["FIPE-20220167"],"award-info":[{"award-number":["FIPE-20220167"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnologico, CNPq, Fundo de Incentivo a Pesquisa do Hospital de Cl\u00ednicas de Porto Alegre","award":["88882.346533\/2019-01"],"award-info":[{"award-number":["88882.346533\/2019-01"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnologico, CNPq, Fundo de Incentivo a Pesquisa do Hospital de Cl\u00ednicas de Porto Alegre","award":["FIPE-20220167"],"award-info":[{"award-number":["FIPE-20220167"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Metabolic dysfunction-associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that thyroid hormone triiodothyronine (T3) regulates hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of type 3 deiodinase (D3) contributes to MAFLD, but its role is not fully understood. Objective: To evaluate the role of D3 in the progression of MAFLD in an animal model. Methodology: Male\/adult Sprague Dawley rats (n = 20) were allocated to a control group (2.93 kcal\/g) and high-fat diet group (4.3 kcal\/g). Euthanasia took place on the 28th week. D3 activity and expression, Uncoupling Protein 2 (UCP2) and type 1 deiodinase (D1) expression, oxidative stress status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured. Results: We observed an increase in D3 activity\/expression (p &lt; 0.001) related to increased thiobarbituric acid reactive substances (TBARS) and carbonyls and diminished reduced glutathione (GSH) in the MAFLD group (p &lt; 0.05). There was a D3-dependent decrease in UCP2 expression (p = 0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group (p &lt; 0.001). Surprisingly, in an environment with lower T3 levels due to high D3 activity, we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydrogenase (GDH) enzymes activity (p &lt; 0.05). Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability and hepatic mitochondrial capacity. The Krebs cycle enzymes were altered as well as endoplasmic reticulum stress. Taken together, these results shed new light on the role of D3 metabolism in MAFLD.<\/jats:p>","DOI":"10.3390\/cells12071022","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T05:34:30Z","timestamp":1679895270000},"page":"1022","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Uncovering Actions of Type 3 Deiodinase in the Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD)"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8588-7362","authenticated-orcid":false,"given":"Rafael Aguiar","family":"Marschner","sequence":"first","affiliation":[{"name":"Endocrine Division, Hospital de Cl\u00ednicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3405-3739","authenticated-orcid":false,"given":"Ana Cristina","family":"Roginski","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Biochemestry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5814-6369","authenticated-orcid":false,"given":"Rafael Teixeira","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Post-Graduate Program in Biochemestry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4453-7227","authenticated-orcid":false,"given":"Larisse","family":"Longo","sequence":"additional","affiliation":[{"name":"Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil"},{"name":"Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio Reis","family":"\u00c1lvares-da-Silva","sequence":"additional","affiliation":[{"name":"Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil"},{"name":"Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre 90035-903, RS, Brazil"},{"name":"Department of Internal Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8942-244X","authenticated-orcid":false,"given":"Simone Magagnin","family":"Wajner","sequence":"additional","affiliation":[{"name":"Endocrine Division, Hospital de Cl\u00ednicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, RS, Brazil"},{"name":"Department of Internal Medicine, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90035-003, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jhep.2016.04.005","article-title":"Non-alcoholic fatty liver disease and cardiovascular risk: Pathophysiological mechanisms and implications","volume":"65","author":"Francque","year":"2016","journal-title":"J. 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