Skip Navigation
Skip to contents

Diabetes Metab J : Diabetes & Metabolism Journal

Search
OPEN ACCESS

Articles

Page Path
HOME > Diabetes Metab J > Ahead-of print > Article
Original Article Basic Research Serotonin Regulates Lipogenesis and Endoplasmic Reticulum Stress in Alcoholic Liver Disease
Inseon Hwang1,2,*orcid , Jung Eun Nam2,*orcid , Wonsuk Choi3, Won Gun Choi4, Eunji Lee5, Hyeongseok Kim5,6, Young-Ah Moon7, Jun Yong Park8orcid , Hail Kim2orcid

DOI: https://doi.org/10.4093/dmj.2024.0215 [Epub ahead of print]
Published online: February 5, 2025
  • 118 Views
  • 10 Download
  • 0 Crossref
  • 0 Scopus
1Department of Biopharmacy, Daejeon Health University, Daejeon, Korea
2Graduate School of Medical Science and Engineering, Biomedical Research Center, Korea Advanced Institute of Science and Technology, Daejeon, Korea
3Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea
4Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
5Department of Medical Science, Chungnam National University College of Medicine, Daejeon, Korea
6Department of Biochemistry, Chungnam National University College of Medicine, Daejeon, Korea
7Department of Molecular Medicine, Inha University College of Medicine, Incheon, Korea
8Department of Internal Medicine, Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Corresponding author:  Inseon Hwang,
Email: ishwang@hit.ac.kr
Jun Yong Park,
Email: drpjy@yuhs.ac
Hail Kim,
Email: hailkim@kaist.edu
*These authors contributed equally to this work.
Received: 26 April 2024   • Accepted: 21 September 2024

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) in vivo 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 (Tph1) knockout mice, liver-specific Htr2a knockout mice, and liver-specific Htr2b 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 Tph1 knockout and liver- specific Htr2a 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.

  • Cite
    CITE
    export Copy
    Close
    Download Citation
    Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

    Format:
    • RIS — For EndNote, ProCite, RefWorks, and most other reference management software
    • BibTeX — For JabRef, BibDesk, and other BibTeX-specific software
    Include:
    • Citation for the content below
    Serotonin Regulates Lipogenesis and Endoplasmic Reticulum Stress in Alcoholic Liver Disease
    Close
Related articles
Hwang I, Nam JE, Choi W, Choi WG, Lee E, Kim H, Moon YA, Park JY, Kim H. Serotonin Regulates Lipogenesis and Endoplasmic Reticulum Stress in Alcoholic Liver Disease. Diabetes Metab J. 2025 Feb 5. doi: 10.4093/dmj.2024.0215. Epub ahead of print.
Received: Apr 26, 2024; Accepted: Sep 21, 2024
DOI: https://doi.org/10.4093/dmj.2024.0215.

Diabetes Metab J : Diabetes & Metabolism Journal
Close layer
TOP