{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:58:46Z","timestamp":1790755126822,"version":"4.1.0"},"reference-count":124,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sino Danish Research and Education Center"},{"name":"Danish National Research Foundation"},{"name":"VILLUM Center for Bioanalytical Sciences at SDU"},{"name":"Danish Ministry of Higher Education and Science"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Non-alcoholic fatty liver disease affects one-fourth of the world\u2019s population. Central to the disease progression is lipid accumulation in the liver, followed by inflammation, fibrosis and cirrhosis. The underlying mechanism behind the early stages of the disease is poorly understood. We have exposed human hepatic HepG2\/C3A cells-based spheroids to 65 \u03bcM oleic acid and 45 \u03bcM palmitic acid and employed proteomics and lipidomics analysis to investigate their effect on hepatocytes. The treatment successfully induced in vivo hallmarks of NAFLD, as evidenced by intracellular lipid accumulation and increased ATP levels. Quantitative lipidome analysis revealed an increase in ceramides, LPC and saturated triglycerides and a decrease in the ratio of PC\/PE, similar to the changes observed in patients\u2019 liver biopsies. The proteomics analysis combined with qPCR showed increased epithelial to mesenchymal transition (EMT) signalling. Activation of EMT was further validated by transcriptomics in TGF-\u03b2 treated spheroids, where an increase in mesenchymal cell markers (N-cadherin and collagen expression) was found. Our study demonstrates that this model system thus closely echoes several of the clinical features of non-alcoholic fatty liver disease and can be used to investigate the underlying molecular changes occurring in the condition.<\/jats:p>","DOI":"10.3390\/cells11203216","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T20:55:11Z","timestamp":1665694511000},"page":"3216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Mapping Proteome and Lipidome Changes in Early-Onset Non-Alcoholic Fatty Liver Disease Using Hepatic 3D Spheroids"],"prefix":"10.3390","volume":"11","author":[{"given":"Helle Sedighi","family":"Frandsen","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark"},{"name":"Sino-Danish College (SDC), University of Chinese Academy of Sciences, 380 Huaibeizhuang, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6800-5092","authenticated-orcid":false,"given":"Joel Mario","family":"Vej-Nielsen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark"},{"name":"Sino-Danish College (SDC), University of Chinese Academy of Sciences, 380 Huaibeizhuang, Beijing 100101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren Elizabeth","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lang","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences, Beijing 101408, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0018-5298","authenticated-orcid":false,"given":"Karoline Lindgaard","family":"Mikkelsen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark"},{"name":"CelVivo ApS, 5491 Blommenslyst, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemette Pr\u00e6stegaard","family":"Thulesen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina Erika","family":"Hagensen","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuquan","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Protein and Peptide Pharmaceuticals & Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China"},{"name":"University of Chinese Academy of Sciences, Beijing 101408, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9876-0061","authenticated-orcid":false,"given":"Adelina","family":"Rogowska-Wrzesinska","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense M, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.jhepr.2019.10.008","article-title":"Lifestyle modification in NAFLD\/NASH: Facts and figures","volume":"1","author":"Hallsworth","year":"2019","journal-title":"JHEP Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41575-019-0144-8","article-title":"Past, present and future perspectives in nonalcoholic fatty liver disease","volume":"16","author":"Sanyal","year":"2019","journal-title":"Nat. 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