{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:20:27Z","timestamp":1790630427997,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"publisher","award":["2017\/26\/E\/NZ5\/00691"],"award-info":[{"award-number":["2017\/26\/E\/NZ5\/00691"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland","award":["MNS 1\/2020"],"award-info":[{"award-number":["MNS 1\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nonalcoholic fatty liver disease is defined as the accumulation of excessive fat in the liver in the absence of excessive alcohol consumption or any secondary cause. Although the disease generally remains asymptomatic, chronic liver inflammation leads to fibrosis, liver cirrhosis, and even to the development of hepatocellular carcinoma (HCC). Fibrosis results from epithelial\u2013mesenchymal transition (EMT), which leads to dedifferentiation of epithelial cells into cells with a mesenchymal-like phenotype. During EMT, epithelial cells with high expression of E-cadherin, influenced by growth factors, cytokines, and inflammatory processes, undergo morphological changes via enhanced expression of, e.g., vimentin, fibronectin, and N-cadherin. An inducer of EMT and, consequently, of fibrosis development is transforming growth factor beta (TGF\u03b2), a pleiotropic cytokine associated with the progression of hepatocarcinogenesis. However, the understanding of the molecular events that direct the development of steatosis into steatohepatitis and liver fibrosis remains incomplete. Our study revealed that both prolonged exposure of hepatocarcinoma cells to fatty acids in vitro and high-fat diet in mice (20 weeks) result in inflammation. Prolonged treatment with fatty acids increased the levels of TGF\u03b2, MMP9, and \u03b2-catenin, important EMT inducers. Moreover, the livers of mice fed a high-fat diet exhibited features of liver fibrosis with increased TGF\u03b2 and IL-1 levels. Increased expression of IL-1 correlated with a decrease in monocyte chemoattractant protein-induced protein 1 (MCPIP1), a negative regulator of the inflammatory response that regulates the stability of proinflammatory transcripts encoding IL-1. Our study showed that a high-fat diet induced EMT by increasing the levels of EMT-activating transcription factors, including Zeb1, Zeb2, and Snail and changed the protein profile to a profile characteristic of the mesenchymal phenotype.<\/jats:p>","DOI":"10.3390\/ijms22031272","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T05:23:05Z","timestamp":1611811385000},"page":"1272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Fatty Acids and a High-Fat Diet Induce Epithelial\u2013Mesenchymal Transition by Activating TGF\u03b2 and \u03b2-Catenin in Liver Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Oliwia","family":"Kwapisz","sequence":"first","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judyta","family":"G\u00f3rka","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Korlatowicz","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3133-3364","authenticated-orcid":false,"given":"Jerzy","family":"Kotlinowski","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7222-0550","authenticated-orcid":false,"given":"Agnieszka","family":"Walig\u00f3rska","sequence":"additional","affiliation":[{"name":"Department of Cell Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7664-250X","authenticated-orcid":false,"given":"Paulina","family":"Marona","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Pydyn","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jurek W.","family":"Dobrucki","sequence":"additional","affiliation":[{"name":"Department of Cell Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0816-3475","authenticated-orcid":false,"given":"Jolanta","family":"Jura","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2716-203X","authenticated-orcid":false,"given":"Katarzyna","family":"Miekus","sequence":"additional","affiliation":[{"name":"Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"Thiery","year":"2009","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrc3419","article-title":"WNT signalling pathways as therapeutic targets in cancer","volume":"13","author":"Anastas","year":"2013","journal-title":"Nat. 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