{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T07:00:02Z","timestamp":1784012402594,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T00:00:00Z","timestamp":1695427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Saud University, Riyadh, Saudi Arabia","award":["RSP2023R261"],"award-info":[{"award-number":["RSP2023R261"]}]},{"name":"Piano di Incentivi per la Ricerca di Ateneo 2020\u20132022, Linea di Intervento 2, \u201cIMYTRA\u201d","award":["RSP2023R261"],"award-info":[{"award-number":["RSP2023R261"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of lipids within hepatocytes, which compromises liver functionality following mitochondrial dysfunction and increased production of reactive oxygen species (ROS). Lipoic acid is one of the prosthetic groups of the pyruvate dehydrogenase complex also known for its ability to confer protection from oxidative damage because of its antioxidant properties. In this study, we aimed to investigate the effects of lipoic acid on lipotoxicity and mitochondrial dynamics in an in vitro model of liver steatosis. HepG2 cells were treated with palmitic acid and oleic acid (1:2) to induce steatosis, without and with 1 and 5 \u00b5M lipoic acid. Following treatments, cell proliferation and lipid droplets accumulation were evaluated. Mitochondrial functions were assessed through the evaluation of membrane potential, MitoTracker Red staining, expression of genes of the mitochondrial quality control, and analysis of energy metabolism by HPLC and Seahorse. We showed that lipoic acid treatment restored membrane potential to values comparable to control cells, as well as protected cells from mitochondrial fragmentation following PA:OA treatment. Furthermore, our data showed that lipoic acid was able to determine an increase in the expression of mitochondrial fusion genes and a decrease in mitochondrial fission genes, as well as to restore the bioenergetics of cells after treatment with palmitic acid and oleic acid. In conclusion, our data suggest that lipoic acid reduces lipotoxicity and improves mitochondrial functions in an in vitro model of steatosis, thus providing a potentially valuable pharmacological tool for NAFLD treatment.<\/jats:p>","DOI":"10.3390\/ijms241914491","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:36:26Z","timestamp":1695551786000},"page":"14491","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["(+)-Lipoic Acid Reduces Lipotoxicity and Regulates Mitochondrial Homeostasis and Energy Balance in an In Vitro Model of Liver Steatosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Lucia","family":"Longhitano","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5264-2935","authenticated-orcid":false,"given":"Federico","family":"Salomone","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Ospedale di Acireale, Azienda Sanitaria Provinciale di Catania, 95024 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Tropea","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7761-0662","authenticated-orcid":false,"given":"Ignazio Alberto","family":"Barbagallo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8678-2183","authenticated-orcid":false,"given":"Giovanni Li","family":"Volti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1639-0966","authenticated-orcid":false,"given":"Giacomo","family":"Lazzarino","sequence":"additional","affiliation":[{"name":"Departmental Faculty of Medicine and Surgery, UniCamillus-Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1016\/j.bbagen.2009.07.026","article-title":"Alpha-lipoic acid as a dietary 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