{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T19:53:15Z","timestamp":1787514795105,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF)","award":["NRF-2023R1A2C2002380"],"award-info":[{"award-number":["NRF-2023R1A2C2002380"]}]},{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF)","award":["NRF-2019R1I1A1A01060819"],"award-info":[{"award-number":["NRF-2019R1I1A1A01060819"]}]},{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF)","award":["NRF-2021R1I1A1A01058855"],"award-info":[{"award-number":["NRF-2021R1I1A1A01058855"]}]},{"name":"Ministry of Education, Science, and Technology","award":["NRF-2023R1A2C2002380"],"award-info":[{"award-number":["NRF-2023R1A2C2002380"]}]},{"name":"Ministry of Education, Science, and Technology","award":["NRF-2019R1I1A1A01060819"],"award-info":[{"award-number":["NRF-2019R1I1A1A01060819"]}]},{"name":"Ministry of Education, Science, and Technology","award":["NRF-2021R1I1A1A01058855"],"award-info":[{"award-number":["NRF-2021R1I1A1A01058855"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Supplementation with fish oil rich in omega-3 polyunsaturated fatty acids (n-3 PUFAs) effectively reduces acute and chronic alcohol-induced hepatic steatosis. We aimed to find molecular mechanisms underlying the effects of n-3 PUFAs in alcohol-induced hepatic steatosis. Because free fatty acid receptor 4 (FFA4, also known as GPR120) has been found as a receptor for n-3 PUFAs in an ethanol-induced liver steatosis model, we investigated whether n-3 PUFAs protect against liver steatosis via FFA4 using AH7614, an FFA4 antagonist, and Ffa4 knockout (KO) mice. N-3 PUFAs and compound A (CpdA), a selective FFA4 agonist, reduced the ethanol-induced increase in lipid accumulation in hepatocytes, triglyceride content, and serum ALT levels, which were not observed in Ffa4 KO mice. N-3 PUFAs and CpdA also reduced the ethanol-induced increase in lipogenic sterol regulatory element-binding protein-1c expression in an FFA4-dependent manner. In Kupffer cells, treatment with n-3 PUFA and CpdA reversed the ethanol-induced increase in tumor necrosis factor-\u03b1, cyclooxygenase-2, and NLR family pyrin domain-containing 3 expression levels in an FFA4-dependent manner. In summary, n-3 PUFAs protect against ethanol-induced hepatic steatosis via the anti-inflammatory actions of FFA4 on Kupffer cells. Our findings suggest FFA4 as a therapeutic target for alcoholic hepatic steatosis.<\/jats:p>","DOI":"10.3390\/ijms25105476","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T06:53:49Z","timestamp":1715928829000},"page":"5476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["N-3 Polyunsaturated Fatty Acids Protect against Alcoholic Liver Steatosis by Activating FFA4 in Kupffer Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Saeromi","family":"Kang","sequence":"first","affiliation":[{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7987-3677","authenticated-orcid":false,"given":"Jung-Min","family":"Koh","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 05505, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8054-8946","authenticated-orcid":false,"given":"Dong-Soon","family":"Im","sequence":"additional","affiliation":[{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Department of Basic Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S0140-6736(05)17870-2","article-title":"Alcohol and public health","volume":"365","author":"Room","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"652","DOI":"10.3350\/cmh.2020.0160","article-title":"Global and regional impacts of alcohol use on public health: Emphasis on alcohol policies","volume":"26","author":"Park","year":"2020","journal-title":"Clin. 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