Decabromodiphenyl ether disturbs hepatic glycolipid metabolism by regulating the PI3K/AKT/GLUT4 and mTOR/PPARγ/RXRα pathway in mice and L02 cells.
Sci Total Environ
; 763: 142936, 2021 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-33138992
ABSTRACT
Decabromodiphenyl ether (BDE-209) is a persistent environmental pollutant that poses great risks to human health and has been associated with glucose and lipid metabolism. However, the mechanisms by which BDE-209 disturbs glycolipid metabolism in the liver remain unclear. Therefore, this study sought to confirm the effects of BDE-209 on glycolipid metabolism in mice livers and L02 cells to elucidate potential mechanisms of action. In vivo BDE-209 exposure caused histological damage and lipid accumulation, elevated glucose, low-density lipoprotein, total cholesterol, and triglyceride levels, and decreased glycogen and high-density lipoprotein levels in mice livers. Moreover, in vitro BDE-209 exposure not only induced L02 cells cytotoxicity (i.e., reduced cell viability and increased LDH leakage and ROS generation) but also increased glucose and triglyceride concentrations in L02 cells. Furthermore, IGF-1, an activator of the PI3K-AKT pathway, markedly inhibited BDE-209-induced glucose concentration increase in L02 cells and antagonized the inhibitory effect of BDE-209 on the PI3K/AKT/GLUT4 pathway by counteracting the changes in the expression levels of p-IRS, AKT, PI3K, p-AKT, and GLUT4. Moreover, GW9662, a PPARγ inhibitor, blocked lipid accumulation and the upregulation of the mTOR/PPARγ/RXRα pathway in L02 cells induced by BDE-209 by relieving the increases in p-mTOR, PPARγ, and RXRα protein expression levels. In summary, this study revealed that BDE-209 disrupted glycolipid metabolism by inhibiting the PI3K/AKT/GLUT4 pathway and activating the mTOR/PPARγ/RXRα pathway.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Agentes_cancerigenos
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositol 3-Quinases
/
PPAR gama
Limite:
Animals
Idioma:
En
Revista:
Sci Total Environ
Ano de publicação:
2021
Tipo de documento:
Article