Changes of flavin-containing monooxygenases and trimethylamine-N-oxide may be involved in the promotion of non-alcoholic fatty liver disease by intestinal microbiota metabolite trimethylamine.

Abstract

Evidence shows that trimethylamine (TMA)/trimethylamine-N-oxide (TMAO) is closely related to non-alcoholic fatty liver disease (NAFLD). The conversion of TMA to TMAO is mainly catalyzed by flavin-containing monooxygenases 3 (FMO3) and FMO1. In this study, we explored the role of TMA in the process of NAFLD. The human NAFLD liver puncture data set GSE89632 and rat TMAO gene chip GSE135856 was downloaded for gene differential expression analysis. Besides, oleic acid (OA) combined with palmitate were used to establish high-fat cell model. TMA, TMAO and FMO1-siRNA were used to stimulate L02 cells. Contents of free fatty acid (FFA), triglyceride (TG), TMAO, FMO1 and unfolded protein response (UPR) related proteins GRP78, XBP1, Derlin-1 were detected. Our results showed that FMO1 and PEG10 were important in the progression of NAFLD. Immunohistochemistry showed that FMO1 in NAFLD liver was increased. In addition, the contents of FFA, TG, FMO1 expression, and TMAO were significantly increased after OA + palmitate and TMA stimulation. However, after silencing FMO1 with siRNA, the expressions of these molecules were decreased. Besides, the protein levels of GRP78, XBP1, Derlin-1 were increased after TMAO treatment (all P < 0.05). In Conclusion, high fat and TMA could induce the expression of FMO1 and its metabolite TMAO. When FMO1 is silenced, the effects of high fat and TMA on TMAO are blocked. And the role of TMAO in NAFLD may be through the activation of UPR.

• Authors: Chunxia Shi, Maohua Pei, Yao Wang, Qian Chen, Pan Cao, Luyi Zhang, Jin Guo, Wei Deng, Luwen Wang, Xun Li, Zuojiong Gong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 594 Pg. 1-7 (02 26 2022) ISSN: 1090-2104 [Electronic] United States
• PMID: 35065293 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Chemical References

• DERL1 protein, human
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Membrane Proteins
• Methylamines
• RNA, Small Interfering
• X-Box Binding Protein 1
• XBP1 protein, human
• Oxygenases
• dimethylaniline monooxygenase (N-oxide forming)
• trimethyloxamine
• trimethylamine

Topics

• Animals
• Cell Line
• Endoplasmic Reticulum Chaperone BiP (biosynthesis)
• Gastrointestinal Microbiome
• Gene Silencing
• Humans
• Immunohistochemistry
• Inflammation
• Male
• Membrane Proteins (biosynthesis)
• Methylamines (chemistry)
• Non-alcoholic Fatty Liver Disease (metabolism)
• Oxygenases (biosynthesis)
• RNA, Small Interfering (metabolism)
• Rats
• Rats, Sprague-Dawley
• X-Box Binding Protein 1 (biosynthesis)