{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:28:05Z","timestamp":1790029685341,"version":"4.0.1"},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H03934"],"award-info":[{"award-number":["22H03934"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of critical liver diseases leading to steatosis, steatohepatitis, fibrosis, and ultimately to liver cirrhosis and hepatic carcinoma. In this study, the effect of palmitic acid (PA), one of the most abundant dietary fatty acids, was investigated using an organ\u2010on\u2010a\u2010chip (OoC) technology on hepatocyte\u2010like cells derived from human\u2010induced pluripotent stem cells (hiPSCs). After 1\u2009week of hepatic maturation, followed by 1\u2009week of exposure, the transcriptomic analysis showed lower liver transcription factor activity. It also revealed that 318 genes were differentially expressed between the control and 0.5\u2010mM PA conditions. The 0.5\u2010mM PA conditions were characterized by the downregulation of hepatic markers (liver transcription factors, phase I and phase II metabolism genes) of lipidic genes (metabolism and transport). In parallel, the 0.5\u2010mM PA treatment upregulated several extracellular matrix genes (such as collagen genes). The physiopathological staining demonstrated no lipid accumulation in our model and confirmed the secretion of collagen in the 0.5\u2010mM PA conditions. However, the production of albumin, the metabolic biotransformation by the cytochrome P450 enzymes, and the biliary acid concentrations were not altered by the PA treatments. Overall, our data illustrated the response to PA characterized by an early stage of dedifferentiation observed at the transcriptomic levels associated with a modification of the collagenic profile but without lipid accumulation. We believe that our model provides new insight of the onset of palmitic lipotoxicity in the early stage of NAFLD.<\/jats:p>","DOI":"10.1002\/jat.4714","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T23:25:38Z","timestamp":1730935538000},"page":"460-471","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Palmitic Acid Induced a Dedifferentiation Profile at the Transcriptome Level: A Collagen Synthesis but no Triglyceride Accumulation in Hepatocyte\u2010Like Cells Derived From Human\u2010Induced Pluripotent Stem Cells Cultivated Inside Organ on a Chip"],"prefix":"10.1002","volume":"45","author":[{"given":"Hanyuan","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemical System Engineering, Graduate School of Engineering The University of Tokyo  Tokyo Japan"},{"name":"CNRS\/IIS IRL 2820; Laboratory for Integrated Micro Mechatronic Systems, Institute of 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