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Recent studies reported that ethanol exposure leads to the activation of prostaglandin signaling via increasing the levels of AA and its metabolites in cardiomyocytes. To test the hypothesis that AA contributes at least in part, to ethanol-induced cardiomyocyte injury, a chronic ethanol feeding model was used, in which male Wistar rats were fed Lieber-Decarli ethanol diet 6.7% (v\/v) or isocaloric control diet for 6 weeks. Gas chromatography analysis indicated that ethanol exposure increased the AA content in rat myocardial phospholipids along with increased protein levels of endoplasmic reticulum (ER) stress markers and a decrease in the level of NADH: ubiquinone oxidoreductase subunit B8, a mitochondrial complex I subunit. In addition, an in vitro model was used in which H9c2 cells, a rat cardiomyoblast cell line, were exposed to AA and\/or ethanol (ET), and markers of steatosis and endoplasmic reticulum stress, and mitochondrial respiration were assessed. Of note, AA supplementation potentiated ethanol-induced steatosis. H9c2 cells receiving ET\u2009+\u2009AA showed an increase in the expression of ER stress markers, including glucose-regulated protein 78 and activating transcription factor 4, compared with controls. Interestingly, compared to ET treatment, ET\u2009+\u2009AA treatment led to a significant decrease in basal respiration and ATP-linked respiration, indicating an impaired mitochondrial respiration in H9c2 cardiomyoblasts. Finally, inhibiting long-chain acyl CoA synthases by Triacsin C attenuated ET\u2009+\u2009AA treatment-induced steatosis but increased mitochondrial respiration in H9c2 cells. Collectively, these data suggested that AA supplementation promotes ethanol-induced steatosis and endoplasmic reticulum stress with a concomitant impairment in mitochondrial respiration in H9c2 cardiomyoblasts, and Triacsin C treatment inhibits steatosis but enhances mitochondrial respiration possibly via altered fatty acid partitioning between synthetic and oxidative processes.<\/jats:p>","DOI":"10.1186\/s12944-025-02792-3","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T15:01:54Z","timestamp":1765897314000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A combination of ethanol and arachidonic acid promotes steatosis and endoplasmic reticulum stress and impairs mitochondrial respiration in H9c2 cardiomyoblasts"],"prefix":"10.1186","volume":"24","author":[{"given":"Weilun","family":"Ai","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"New","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol A.","family":"Casey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viswanathan","family":"Saraswathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"2792_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-1039-y","volume":"18","author":"H Kawashima","year":"2019","unstructured":"Kawashima H. 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