Title:Effect of Antidepressants on Non-alcoholic Fatty Liver Disease and their Underlying Mechanism
Volume: 32
Issue: 35
Author(s): Hailing Peng, Yumin Qing, Liu Han, Shifeng Fu, Jianglei Li, Siyi Wang, Deliang Liu, Lini Liu*Yuyong Tan*
Affiliation:
- Department of Psychiatry, The Second People's Hospital of Hunan Province, Changsha, 410011, China
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
- Research Center of Digestive Disease, Central South University, Changsha, 410011, China
Keywords:
Depression, non-alcoholic fatty liver disease, mirtazapine, pathogenesis, signaling pathway, lipid droplets.
Abstract:
Introduction: The 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.
Methods: Inpatients 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.
Results: Logistic 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.
Conclusion: Age, 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.
