{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T10:51:04Z","timestamp":1792752664858,"version":"4.5.0"},"reference-count":44,"publisher":"Korean Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:00:00Z","timestamp":1738713600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-00166199"],"award-info":[{"award-number":["RS-2022-00166199"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["002475581G0003101"],"award-info":[{"award-number":["002475581G0003101"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1C1C1005109"],"award-info":[{"award-number":["2021R1C1C1005109"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00222910"],"award-info":[{"award-number":["RS-2023-00222910"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020M3A9E4038695"],"award-info":[{"award-number":["2020M3A9E4038695"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"<jats:p>Background: Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine neurotransmitter that has various functions in central and peripheral tissues. While 5-HT is known to regulate various biological processes in liver, direct role of 5-HT and its receptors, especially 5-HT receptor 2A (HTR2A) and HTR2B, in development and progression of alcoholic liver disease (ALD) &lt;i&gt;in vivo&lt;\/i&gt; is not well understood.Methods: Blood 5-HT level was measured from both human ALD patients and ethanol (EtOH) diet-fed mouse models. Gut-specific tryptophan hydroxylase 1 (&lt;i&gt;Tph1&lt;\/i&gt;) knockout mice, liver-specific &lt;i&gt;Htr2a&lt;\/i&gt; knockout mice, and liver-specific &lt;i&gt;Htr2b&lt;\/i&gt; knockout mice were fed with EtOH diet. Then we evaluated liver damage, hepatic steatosis, endoplasmic reticulum (ER) stress, and inflammation.Results: Blood 5-HT concentrations are increased in both humans and mice with ALD. Both gut-specific &lt;i&gt;Tph1&lt;\/i&gt; knockout and liver- specific &lt;i&gt;Htr2a&lt;\/i&gt; knockout mice are resistant to steatosis by down-regulating lipogenic pathways in liver of chronic EtOH diet-fed mice. Moreover, genetic inhibition of both gut-derived serotonin (GDS) synthesis and hepatic HTR2A signaling prevents ER stress in liver of chronic EtOH diet-fed mice. Additionally, we found that ablation of HTR2A signaling protects against disease progression by attenuating liver injury and inflammation in chronic plus binge EtOH diet-fed mice. Also, inhibiting HTR2A signaling ameliorates alcohol-induced liver injury and ER stress in an acute EtOH diet-fed mice model.Conclusion: GDS directly regulates lipogenesis and ER stress via signaling through hepatic HTR2A in the context of ALD. Inhibiting HTR2A signaling protects against alcohol-induced steatosis, liver injury and disease progression in various ALD mouse models and may also provide a novel therapeutic strategy for ALD.<\/jats:p>","DOI":"10.4093\/dmj.2024.0215","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T00:34:56Z","timestamp":1738715696000},"page":"798-811","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Serotonin Regulates Lipogenesis and Endoplasmic Reticulum Stress in Alcoholic Liver Disease"],"prefix":"10.4093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5191-4525","authenticated-orcid":true,"given":"Inseon","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7021-8406","authenticated-orcid":true,"given":"Jung Eun","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonsuk","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won Gun","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunji","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeongseok","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ah","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6324-2224","authenticated-orcid":true,"given":"Jun 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