{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T09:55:47Z","timestamp":1771667747749,"version":"3.50.1"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T00:00:00Z","timestamp":1536624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/BIM-MET\/4447\/2014; COMPETE: POCI-01-0145-FEDER-016784"],"award-info":[{"award-number":["PTDC\/BIM-MET\/4447\/2014; COMPETE: POCI-01-0145-FEDER-016784"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prevention of hepatic fat accumulation may be an important approach for liver diseases due to the increased relevance of hepatic steatosis in this field. This study was conducted to investigate the effects of the antioxidant \u03b1-lipoic acid (\u03b1-LA) on hepatic steatosis, hepatocellular function, and oxidative stress in a model of type 2 diabetes fed with a high fat diet (HFD). Goto-Kakizaki rats were randomly divided into four groups. The first group received only a standard rat diet (control GK) including groups 2 (HFD), 3 (vehicle group), and 4 (\u03b1-LA group), which were given HFD, ad libitum during three months. Wistar rats are the non-diabetic control group. Carbohydrate and lipid metabolism, liver function, plasma and liver tissue malondialdehyde (MDA), liver GSH, tumor necrosis factor-\u03b1 (TNF-\u03b1) and nuclear factor E2 (erythroid-derived 2)-related factor-2 (Nrf2) levels were assessed in the different groups. Liver function was assessed using quantitative hepatobiliary scintigraphy, serum aspartate, and alanine aminotransferases (AST, ALT), alkaline phosphatase, gamma-glutamyltranspeptidase, and bilirubin levels. Histopathologically steatosis and fibrosis were evaluated. Type 2 diabetic animals fed with HFD showed a marked hepatic steatosis and a diminished hepatic extraction fraction and both were fully prevented with \u03b1-LA. Plasma and liver tissue MDA and hepatic TNF-\u03b1 levels were significantly higher in the HFD group when compared with the control group and significantly lower in the \u03b1-LA group. Systemic and hepatic cholesterol, triglycerides, and serum uric acid levels were higher in hyperlipidemic GK rats and fully prevented with \u03b1-LA. In addition, nuclear Nrf2 activity was significantly diminished in GK rats and significantly augmented after \u03b1-LA treatment. In conclusion, \u03b1-LA strikingly ameliorates steatosis in this animal model of diabetes fed with HFD by decrementing the inflammatory marker TNF-\u03b1 and reducing oxidative stress. \u03b1-LA might be considered a useful therapeutic tool to prevent hepatic steatosis by incrementing antioxidant defense systems through Nrf2 and consequently decreasing oxidative stress and inflammation in type 2 diabetes.<\/jats:p>","DOI":"10.3390\/ijms19092706","type":"journal-article","created":{"date-parts":[[2018,9,11]],"date-time":"2018-09-11T11:40:02Z","timestamp":1536666002000},"page":"2706","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Lipoic Acid Prevents High-Fat Diet-Induced Hepatic Steatosis in Goto Kakizaki Rats by Reducing Oxidative Stress Through Nrf2 Activation"],"prefix":"10.3390","volume":"19","author":[{"given":"Cristina Maria","family":"Sena","sequence":"first","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Coimbra; Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"},{"name":"iCBR, Faculty of Medicine, University of Coimbra; Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"}]},{"given":"Maria Augusta","family":"Cipriano","sequence":"additional","affiliation":[{"name":"Pathological Anatomy, University Hospitals of Coimbra, 3000-457 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7202-1650","authenticated-orcid":false,"given":"Maria Filomena","family":"Botelho","sequence":"additional","affiliation":[{"name":"iCBR, Faculty of Medicine, University of Coimbra; Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"}]},{"given":"Raquel Maria","family":"Sei\u00e7a","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Coimbra; Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"},{"name":"iCBR, Faculty of Medicine, University of Coimbra; Azinhaga de Santa Comba, Celas, 3000-548 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6184","DOI":"10.3390\/ijms15046184","article-title":"Obesity and its metabolic complications: The role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease","volume":"15","author":"Jung","year":"2014","journal-title":"Int. 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