Gut microbiota-derived trimethylamine induces oxidative stress, inflammation, and apoptosis in HepG2 cells

Abstract

Abstract: Objective This study aims to evaluate the effects of TMA on hepatocytes. Methods HepG2 cells were treated with different concentrations (0, 50 μM, and 10 mM) of TMA for 24 and 48 hours. Cell viability, the conversion of TMA to TMAO, and the expression of flavin-containing monooxygenase (FMO) genes were assessed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) were used to detect TMAO levels, while oil red O staining was used to evaluate lipid deposition. Oxidative stress and inflammatory responses were analyzed by DHE staining and ELISA. Cell apoptosis was detected by flow cytometry and western blotting (WB). Results High concentrations of TMA significantly reduced the viability of HepG2 cells in a dose- and time-dependent manner. The conversion of TMA to TMAO increased in a concentration-and time-dependent manner, accompanied by upregulation of FMO1, FMO2, and FMO3 gene expression. Although TMA itself did not significantly affect lipid metabolism, it significantly promoted lipid droplet formation when combined with fatty acids. Additionally, TMA induced oxidative stress, inflammation, and apoptosis in HepG2 cells. Conclusion TMA may indirectly accelerate the progression of non-alcoholic fatty liver disease (NAFLD) by inducing oxidative stress, inflammation, and apoptosis.

Key words: Non-alcoholic fatty liver disease, Trimethylamine, Trimethylamine-oxide, Flavin-containing mono-adducted oxidase, Lipid metabolism, Apoptosis

ZHANG Qiu-ling, YAO Li-chao, SHE Sha, DAI Kai, LI Xun. Gut microbiota-derived trimethylamine induces oxidative stress, inflammation, and apoptosis in HepG2 cells[J]. Chinese Hepatolgy, 2026, 31(5): 711-717.

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