Hepatocellular cystathionine γ lyase/hydrogen sulfide attenuates nonalcoholic fatty liver disease by activating farnesoid X receptor

Hepatology, Год журнала: 2022, Номер 76(6), С. 1794 - 1810

Опубликована: Май 19, 2022

Hydrogen sulfide (H2 S) plays a protective role in NAFLD. However, whether cystathionine γ lyase (CSE), dominant H2 S generating enzyme hepatocytes, has the pathogenesis of NAFLD is currently unclear.We showed that CSE protein expression dramatically downregulated, especially fibrotic areas, livers from patients with In high-fat diet (HFD)-induced mice or an oleic acid-induced hepatocyte model, CSE/H2 pathway also downregulated. To illustrate regulatory for NAFLD, we generated hepatocyte-specific knockout mouse (CSELKO ). Feeding HFD to CSELKO mice, they more hepatic lipid deposition increased activity fatty acid de novo synthesis pathway, insulin resistance, and higher gluconeogenic ability compared CSELoxp control mice. By contrast, donor treatment attenuated these phenotypes. Furthermore, protection conferred by was blocked farnesoid X receptor (FXR) knockdown. Consistently, serum deoxycholic lithocholic (FXR antagonists) were increased, tauro-β-muricholic activation elevated) reduced . promoted post-translation modification (sulfhydration) FXR at Cys138/141 sites, thereby enhancing its modulate target genes related glucose metabolism, inflammation, fibrosis. Sulfhydration proteomics patients' supported modulation noted mice.FXR sulfhydration post-translational affected endogenous may promote attenuate Hepatic deficiency promotes development nonalcoholic steatohepatitis. The interaction between be amenable therapeutic drug

Язык: Английский

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Blood ethylene oxide, systemic inflammation, and serum lipid profiles: Results from NHANES 2013–2016

Chemosphere, Год журнала: 2022, Номер 299, С. 134336 - 134336

Опубликована: Март 22, 2022

Язык: Английский

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Mouse models of nonalcoholic fatty liver disease (NAFLD): pathomechanisms and pharmacotherapies

International Journal of Biological Sciences, Год журнала: 2022, Номер 18(15), С. 5681 - 5697

Опубликована: Янв. 1, 2022

The prevalence of non-alcoholic fatty liver disease (NAFLD) increases year by year, and as a consequence, NAFLD has become one the most prevalent diseases worldwide.Unfortunately, no pharmacotherapies for have been approved United States Food Drug Administration despite promising pre-clinical benefits; this situation highlights urgent need to explore new therapeutic targets discovery effective drugs.The mouse is commonly used models study human develop novel due its small size, low-cost ease in genetic engineering.Different are simulate various stages induced dietary and/or intervention.In review, we summarize newly described patho-mechanisms review preclinical (based on method induction) appraises use these anti-NAFLD drug discovery.This article will provide useful resource researchers select appropriate model research based question being addressed.

Язык: Английский

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Hepatic nonvesicular cholesterol transport is critical for systemic lipid homeostasis

Nature Metabolism, Год журнала: 2023, Номер 5(1), С. 165 - 181

Опубликована: Янв. 16, 2023

Язык: Английский

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Rational combination therapy for NASH: Insights from clinical trials and error

Journal of Hepatology, Год журнала: 2023, Номер 78(5), С. 1073 - 1079

Опубликована: Янв. 2, 2023

Язык: Английский

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