Ubiquitin-specific peptidase 10 ameliorates hepatic steatosis in nonalcoholic steatohepatitis model by restoring autophagic activity.
Dig Liver Dis
; 54(8): 1021-1029, 2022 08.
Article
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| MEDLINE
| ID: mdl-35288065
ABSTRACT
BACKGROUND:
Nonalcoholic steatohepatitis (NASH) is a critical event in the progression of nonalcoholic fatty liver disease (NAFLD). Steatosis induces lipotoxicity, driving the transition of simple fatty liver (NAFL) to NASH. Autophagy affects NAFLD by improving steatosis.AIM:
To investigate whether ubiquitin-specific peptidase (USP)10 alleviates hepatic steatosis through autophagy.METHODS:
A methionine-choline-deficient diet (MCDD) and choline-deficient diet (CDD) were used to model rodent NASH and NAFL, respectively. HepG2 cells were treated with palmitic acid to model hepatocellular steatosis. A viral carrier was used to regulate the USP10 level. Real-time fluorescence quantitative polymerase chain reaction, western blotting, histology, and electron microscopy were used to detect autophagic activity and steatosis.RESULTS:
In vivo, a time-dependent correlation of USP10 and autophagic activity in the liver was found during NAFLD (including NAFL and NASH) modeling. After 8 weeks of modeling, the autophagic activity of NASH was lower than that of the healthy controls and those with NAFL. USP10 could promote autophagy-related pathways and molecules and increase the synthesis of autophagosomes in NASH, improving steatosis, inflammation, and fibrosis. In vitro, autophagy inhibitors reversed the lipid-lowering effect of USP10 without decreasing the level of fatty acid ß-oxidation.CONCLUSION:
USP10 ameliorated histological steatosis, inflammation, and fibrosis. USP10 alleviated hepatic steatosis in NASH in an autophagy-dependent manner.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad del Hígado Graso no Alcohólico
Límite:
Animals
Idioma:
En
Revista:
Dig Liver Dis
Asunto de la revista:
GASTROENTEROLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
China