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Gut-Derived Serotonin Contributes to the Progression of Non-Alcoholic Steatohepatitis via the Liver HTR2A/PPARγ2 Pathway by Wang, Lulu; Fan, Xiangcheng; Han, Jichun; Cai, Minxuan; Wang, Xiaozhong; Wang, Yan; Shang, Jing is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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The precipitous increase in occurrence of non-alcoholic steatohepatitis (NASH) is a serious threat to public health worldwide. The pathogenesis of NASH has not yet been thoroughly studied. We aimed to elucidate the interplay between serotonin (5-hydroxytryptamine, 5-HT) and NASH. The serum 5-HT levels in patients with non-alcoholic fatty liver disease (NAFLD) and a rat fed with high fat-sucrose diet (HFSD) were evaluated using liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF MS)/MS. The peripheral Tph1 inhibitor, LP533401, and a tryptophan (TRP)-free diet were administered to rats with NASH, induced by HFSD. BRL-3A cells were treated with 1 mM free fatty acids (FFAs) and/or 50 μM 5-HT, and then small interfering RNA (siRNA) targeting the 5-HT2A receptor (HTR2A) and the PPARγ pharmaceutical agonist, pioglitazone, were applied. We found a marked correlation between 5-HT and NASH. The absence of 5-HT, through the pharmaceutical blockade of Tph1 (LP533401) and dietary control (TRP-free diet), suppressed hepatic lipid load and the expression of inflammatory factors (__Tnfα__, __Il6__, and __Mcp-1__). In BRL-3A cells, 50 μM 5-HT induced lipid accumulation

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Author

Wang, Lulu; Fan, Xiangcheng; Han, Jichun; Cai, Minxuan; Wang, Xiaozhong; Wang, Yan; Shang, Jing

Publisher

Frontiers; Frontiers Media SA; Frontiers Media S.A.; Lausanne: Frontiers Media S.A., 2010- (ISSN 1663-9812)

Published

2020

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)