Effects of glyphosate exposure on western diet-induced non-alcoholic fatty liver disease in mice

We evaluated whether glyphosate promotes western diet (WD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed WD and received intragastrical glyphosate (0.05, 5 or 50 mg/kg) for 6 months. Glyphosate did not promote WD-induced obesity, hypercholesterolemia, glucose intoler...

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Detalles Bibliográficos
Autores: Romualdo, Guilherme R. [UNESP], Valente, Letícia Cardoso [UNESP], dos Santos, Ana Carolina Sprocatti [UNESP], Grandini, Núbia Alves [UNESP], Camacho, Camila Renata Correa [UNESP], Vinken, Mathieu, Cogliati, Bruno, Hou, De-Xing, Barbisan, Luís Fernando [UNESP]
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Brasil
Institución:Universidade Estadual Paulista (UNESP)
Repositorio:Repositório Institucional da UNESP
Idioma:inglés
OAI Identifier:oai:repositorio.unesp.br:11449/302301
Acceso en línea:http://dx.doi.org/10.1016/j.etap.2023.104286
https://hdl.handle.net/11449/302301
Access Level:acceso abierto
Palabra clave:C57BL/6J mice
Glyphosate
Inflammation
Non-alcoholic fatty liver disease
Oxidative stress
Descripción
Sumario:We evaluated whether glyphosate promotes western diet (WD)-induced non-alcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed WD and received intragastrical glyphosate (0.05, 5 or 50 mg/kg) for 6 months. Glyphosate did not promote WD-induced obesity, hypercholesterolemia, glucose intolerance, hepatic steatosis, and fibrosis. Nonetheless, the higher dose (50 mg) enhanced hepatic CD68+ macrophage density, p65, TNF-α, and IL-6 protein levels. Furthermore, this dose decreased hepatic Nrf2 levels, while enhancing lipid peroxidation in the liver and adipose tissue. Hepatic transcriptome revealed that glyphosate at 50 mg upregulated 212 genes and downregulated 731 genes. Genes associated with oxidative stress and inflammation were upregulated, while key cell cycle-related genes were downregulated. Our results indicate that glyphosate exposure – in a dose within the toxicological limits - impairs hepatic inflammation/redox dynamics in a NAFLD microenvironment.