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Despite the increasing prevalence of NAFLD, the exact cellular and molecular mechanisms remain unclear, and effective therapeutic strategies are still limited. In vitro models of NAFLD are critical to understanding the pathogenesis and searching for effective therapies; thus, we evaluated the effects of free fatty acids (FFAs) on NAFLD hallmarks and their association with the modulation of Annexin A2 (ANXA2) and Keratin 17 (KRT17) in HepG2 cells. Our results show that oleic and palmitic acids can differentially induce intracellular lipid accumulation, cell death, and promote oxidative stress by increasing lipid peroxidation, protein carbonylation, and antioxidant defense depletion. Moreover, a markedly increased expression of inflammatory cytokines demonstrated the activation of inflammation pathways associated with lipotoxicity and oxidative stress. ANXA2 overexpression and KRT17 nuclear translocation were also observed, supporting the role of both molecules in the progression of liver disease. Taken together, these data provide insights into the interplay between ANXA2 and KRT17 in NAFLD, paving the way for understanding molecular mechanisms involved with the disease and developing new therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijms25179591","type":"journal-article","created":{"date-parts":[[2024,9,4]],"date-time":"2024-09-04T08:46:22Z","timestamp":1725439582000},"page":"9591","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Oxidative Stress and Annexin A2 Differential Expression in Free Fatty Acids-Induced Non-Alcoholic Fatty Liver Disease in HepG2 Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Vin\u00edcius Marques","family":"Arruda","sequence":"first","affiliation":[{"name":"Laboratory of Metabolic Biochemistry and Redox Processes, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"},{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela Tolentino","family":"Azevedo","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Biochemistry and Redox Processes, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"},{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J\u00falia Maia Gon\u00e7alves","family":"Granato","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Biochemistry and Redox Processes, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6838-5889","authenticated-orcid":false,"given":"Andr\u00e9 Carlos Pereira","family":"Matos","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-1403","authenticated-orcid":false,"given":"Thaise Gon\u00e7alves","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Laboratory of Genetics and Biotechnology, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-7355","authenticated-orcid":false,"given":"Joyce Ferreira da Costa","family":"Guerra","sequence":"additional","affiliation":[{"name":"Laboratory of Metabolic Biochemistry and Redox Processes, Institute of Biotechnology, Federal University of Uberlandia, Patos de Minas 38700-002, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s13679-018-0317-8","article-title":"Epidemiology of Obesity in Adults: Latest Trends","volume":"7","author":"Inoue","year":"2018","journal-title":"Curr. 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