{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T10:33:52Z","timestamp":1793010832986,"version":"4.5.0"},"reference-count":0,"publisher":"The Scientific and Technological Research Council of Turkey (TUBITAK-ULAKBIM) - DIGITAL COMMONS JOURNALS","issue":"3","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Turkish Journal of Biology"],"abstract":"<jats:p>Background\/aim: Polyunsaturated fatty acids (PUFAs) and the hepatic cholinergic axis are critical regulators of lipid metabolism and inflammatory signaling; however, their time-dependent interplay in hepatocytes remains incompletely understood. Clarifying how n-6 and n-3 PUFAs interact with cholinergic pathways may provide mechanistic insight into metabolic dysfunction-associated steatotic liver disease (MASLD).\nMaterials and methods: HepG2 cells were used to examine the combined effects of butyrylcholinesterase (BChE) overexpression and PUFA exposure. Cells were treated with linoleic acid (LA; n-6) or \u03b1-linolenic acid (\u03b1-LA; n-3) for 24 or 48 h. Gene expression analyses were performed to assess pathways involved in de novo lipogenesis, \u03b2-oxidation, cholinergic signaling, and inflammatory responses. Cholinesterase activities were measured enzymatically, secreted cytokines were profiled, and molecular docking simulations were performed to evaluate potential \u03b1-LA interactions with the \u03b17 nicotinic acetylcholine receptor (\u03b17 nAChR) and M3 muscarinic acetylcholine receptor (M3 mAChR).\nResults: An early antilipogenic profile and changes suggestive of increased fatty-acid oxidation (\u2193SREBP-1c, \u2193ACC1, and \u2191CPT1A) were induced by \u03b1-LA at 24 h and were partially attenuated by 48 h. LA exhibited a biphasic pattern characterized by modest early suppression followed by a pronounced proinflammatory profile at 48 h (\u2191TNF, \u2191IL6, and \u2191COX-2). BChE overexpression was associated with increased expression of lipogenic and triglyceride-related genes, whereas cotreatment with PUFAs resulted in time- and class-specific modulation. Cholinergic markers exhibited divergent expression patterns: BCHE + \u03b1-LA increased CHAT and CHRNA7 expression at 48 h, whereas ACHE mRNA expression increased under both BCHE + LA and BCHE + \u03b1-LA conditions. Enzymatic analyses demonstrated increased total cholinesterase activity in the BChE and \u03b1-LA groups, while molecular docking supported the potential accommodation of \u03b1-LA within the binding pockets of \u03b17 nAChR and M3 mAChR.\nConclusion: PUFA class and exposure duration jointly shape hepatocellular metabolic and inflammatory states, with cholinergic signaling acting as a modulatory node relevant to MASLD.<\/jats:p>","DOI":"10.55730\/1300-0152.2806","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T07:25:07Z","timestamp":1782458707000},"page":"245-258","source":"Crossref","is-referenced-by-count":0,"title":["An in vitro mechanistic study of cholinergic-associated mechanisms relevant to MASLD in HepG2 cells"],"prefix":"10.55730","volume":"50","author":[{"given":"GAMZE","family":"S\u00d6NMEZ","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00dcSL\u00dcM","family":"G\u00d6K","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"SUAT","family":"SARI","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EBRU","family":"BODUR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"34691","published-online":{"date-parts":[[2026,6,18]]},"container-title":["Turkish Journal of Biology"],"original-title":[],"language":"en","deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T09:51:50Z","timestamp":1793008310000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.tubitak.gov.tr\/biology\/vol50\/iss3\/7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":0,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6,18]]}},"URL":"https:\/\/doi.org\/10.55730\/1300-0152.2806","relation":{},"ISSN":["1300-0152"],"issn-type":[{"value":"1300-0152","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]}}}