Evidence map›Paper›PMID 39238390›Full record

ArticleCurrent medicinal chemistry2025

Effect of Antidepressants on Non-alcoholic Fatty Liver Disease and their Underlying Mechanism.

Hailing Peng, Yumin Qing, Liu Han, Shifeng Fu, Jianglei Li, Siyi Wang, Deliang Liu, Lini Liu, Yuyong Tan

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Article in Current medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Hailing PengDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Yumin QingDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Liu HanDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Shifeng FuDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Jianglei LiDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Siyi WangDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Deliang LiuDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Lini LiuDepartment of Psychiatry, The Second People's Hospital of Hunan Province, Changsha, 410011, China.
Yuyong TanDepartment of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.

Funding

Natural Science Foundation of Hunan Province 2022JJ30837Scientific Research Project of the Hunan Provincial Health Commission 202103030980
6 · The paper itself

Abstract

introductionThe high prevalence of non-alcoholic Fatty Liver Disease (NAFLD), a chronic progressive disease characterized by hepatic steatosis, poses a serious burden to human health. Depression and NAFLD share some common pathogenic mechanisms, and patients with depression are at an increased risk of NAFLD. The drug mirtazapine is commonly used in the treatment of depression, but it can also cause liver damage. However, whether mirtazapine induces or aggravates NAFLD remains uncertain. Thus, we evaluated the risk factors for NAFLD in patients with depression and the effects of mirtazapine on NAFLD in vitro.

methodsInpatients diagnosed with depression at the Second Xiangya Hospital of Central South University between 2019 and 2022 were included in this study, and NAFLD was determined using an abdominal ultrasound examination. The risk factors for the development of NAFLD in patients with depression were analyzed using logistic regression analysis. AML-12 and MIHA cell lines were used to observe the effects of mirtazapine on NAFLD using oil red O staining. RT-qPCR and Western blotting were used to explore the molecular mechanism behind NAFLD development induced by mirtazapine.

resultsLogistic regression analysis showed that older age, use of mirtazapine or fluoxetine, longer duration of antidepressant use, and combined hyperlipidemia or T2DM were risk factors for NAFLD in patients with depression. In vitro experiments revealed a subsequent increase in the content of intracellular lipid droplets as mirtazapine concentration increased. Mechanistic studies showed that mirtazapine increased the expressions of TLR4, MyD88, IFN-γ, IL-1β, IL-6, and TNF-α mRNA in hepatocytes and the expressions of TLR4, MyD88, and p-NF-κB-p65 proteins in a dose-dependent manner.

conclusionAge, antidepressant type, duration of antidepressant use, and comorbidities could be risk factors for NAFLD in patients with depression. Furthermore, mirtazapine can cause steatosis in both AML-12 and MIHA cell lines and may promote the development of NAFLD through the TLR4/MyD88/NF-κB signaling pathway. This study lays a solid foundation for further research on depression and NAFLD and can contribute to the prevention and treatment of these two diseases.

Indexed as

Antidepressive AgentsMirtazapineNon-alcoholic Fatty Liver DiseaseAdultAgedDepressionFemaleHumansMaleMiddle AgedMyeloid Differentiation Factor 88Risk FactorsToll-Like Receptor 4Antidepressive AgentsMirtazapineMyeloid Differentiation Factor 88TLR4 protein, humanToll-Like Receptor 4Depressionlipid droplets.mirtazapinenon-alcoholic fatty liver diseasepathogenesissignaling pathway

Identifiers

PMID39238390

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.