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While olfactory receptors are primarily known for detecting odorants, emerging evidence suggests that they also influence liver lipid metabolism. This study generated a mouse model with a specific knockout of olfactory receptor 23 (MOR23) to investigate its role in hepatic steatosis. MOR23 knockout mice on a normal diet showed a slight increase in liver weight compared to wild\u2010type (WT) mice. When fed a high\u2010fat diet (HFD), these knockout mice exhibited accelerated hepatic steatosis, indicated by increased liver weight and hepatic triglyceride levels. Our findings suggest that the cyclic adenosine monophosphate\/protein kinase A\/AMP\u2010activated protein kinase pathway is involved in the role of MOR23, leading to the upregulation of peroxisome proliferator\u2010activated receptor \u03b1, peroxisome proliferator\u2010activated receptor\u2010\u03b3 coactivator 1\u2010\u03b1, and their target \u03b2\u2010oxidation genes in the liver. MOR23 also appeared to regulate lipogenesis and free fatty acid uptake in HFD\u2010fed mice, potentially by influencing sterol regulatory element\u2010binding protein 1 activity. Notably, administering a potential MOR23 ligand, cedrene, attenuated hepatic steatosis in WT mice, but these effects were largely nullified in MOR23 knockout mice. These findings provide valuable insights into the in\u00a0vivo role of MOR23 in hepatic steatosis development.<\/jats:p>","DOI":"10.1096\/fj.202401468rr","type":"journal-article","created":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T06:49:22Z","timestamp":1729147762000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>MOR23<\/scp>\n                    deficiency exacerbates hepatic steatosis in mice"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8842-952X","authenticated-orcid":false,"given":"Wesuk","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0746-369X","authenticated-orcid":false,"given":"Suhjin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9126-2088","authenticated-orcid":false,"given":"Jiyun","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9843-0089","authenticated-orcid":false,"given":"Dabin","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, BK21 FOUR Yonsei University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9515-3605","authenticated-orcid":false,"given":"Han\u2010Woong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Life Science and Biotechnology Yonsei University, Gemcro, Inc.  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