Liver cyclophilin D deficiency inhibits the progression of early NASH by ameliorating steatosis and inflammation.
Biochem Biophys Res Commun
; 594: 168-176, 2022 02 26.
Article
em En
| MEDLINE
| ID: mdl-35085894
ABSTRACT
Cyclophilin D (CypD) can stimulate the opening of the membrane permeability transition pore (mPTP) and regulate mitochondrial function. Whole-body knockout of CypD improved high fat diet-induced hepatic steatosis by reducing the excess opening of the mPTP and lipid deposition. However, whether CypD significantly ameliorates nonalcoholic steatohepatitis (NASH) has not been studied. Therefore, we established liver-specific CypD knockout (CypD LKO) mice and fed a HFHC diet to induce NASH. Compared with the wild-type mice, the CypD LKO not only showed improved lipid deposition and insulin resistance by increasing fatty acid oxidation but also displayed ameliorated hepatic inflammation, although the symptoms of fibrosis in the NASH model were not significantly improved. In addition, we used bile duct ligation (BDL) or a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet to induce cholestatic disease and found that CypD LKO had also no significant effect on acute fibrosis. Thus, CypD LKO can inhibit the progression of early NASH by ameliorating steatosis and inflammatory symptoms. These results suggest a new strategy for the treatment of early NASH.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepatócitos
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Fígado Gorduroso
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Hepatopatia Gordurosa não Alcoólica
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Peptidil-Prolil Isomerase F
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Fígado
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article