Glyphosate-induced autophagy inhibition results in hepatic steatosis via mediating epigenetic reprogramming of PPARα in roosters.
Environ Pollut
; 324: 121394, 2023 May 01.
Article
en En
| MEDLINE
| ID: mdl-36906059
ABSTRACT
Glyphosate (Gly) is the most widely used herbicide with well-defined hepatotoxic effects, but the underlying mechanisms of Gly-induced hepatic steatosis remain largely unknown. In this study, a rooster model combined with primary chicken embryo hepatocytes was established to dissect the progresses and mechanisms of Gly-induced hepatic steatosis. Data showed that Gly exposure caused liver injury with disrupted lipid metabolism in roosters, manifested by significant serum lipid profile disorder and hepatic lipid accumulation. Transcriptomic analysis revealed that PPARα and autophagy-related pathways played important roles in Gly-induced hepatic lipid metabolism disorders. Further experimental results suggested that autophagy inhibition was involved in Gly-induced hepatic lipid accumulation, which was confirmed by the effect of classic autophagy inducer rapamycin (Rapa). Moreover, data substantiated that Gly-mediated autophagy inhibition caused nuclear increase of HDAC3, which altered epigenetic modification of PPARα, leading to fatty acid oxidation (FAO) inhibition and subsequently lipid accumulation in the hepatocytes. In summary, this study provides novel evidence that Gly-induced autophagy inhibition evokes the inactivation of PPARα-mediated FAO and concomitant hepatic steatosis in roosters by mediating epigenetic reprogramming of PPARα.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
PPAR alfa
/
Hígado Graso
Límite:
Animals
Idioma:
En
Revista:
Environ Pollut
Asunto de la revista:
SAUDE AMBIENTAL
Año:
2023
Tipo del documento:
Article
Pais de publicación:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
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REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM