Hepatic FOXA3 overexpression prevents Western diet-induced obesity and MASH through TGR5.
J Lipid Res
; 65(4): 100527, 2024 Apr.
Article
em En
| MEDLINE
| ID: mdl-38447926
ABSTRACT
Forkhead transcription factor 3 (FOXA3) has been shown to regulate metabolism and development. Hepatic FOXA3 is reduced in obesity and fatty liver disease. However, the role of hepatic FOXA3 in regulating obesity or steatohepatitis remains to be investigated. In this work, C57BL/6 mice were i.v. injected with AAV8-ALB-FOXA3 or the control virus. The mice were then fed a chow or Western diet for 16 weeks. The role of hepatic FOXA3 in energy metabolism and steatohepatitis was investigated. Plasma bile acid composition and the role of Takeda G protein-coupled receptor 5 (TGR5) in mediating the metabolic effects of FOXA3 were determined. Overexpression of hepatic FOXA3 reduced hepatic steatosis in chow-fed mice and attenuated Western diet-induced obesity and steatohepatitis. FOXA3 induced lipolysis and inhibited hepatic genes involved in bile acid uptake, resulting in elevated plasma bile acids. The beneficial effects of hepatic FOXA3 overexpression on Western diet-induced obesity and steatohepatitis were abolished in Tgr5-/- mice. Our data demonstrate that overexpression of hepatic FOXA3 prevents Western diet-induced obesity and steatohepatitis via activation of TGR5.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Acoplados a Proteínas G
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Fator 3-gama Nuclear de Hepatócito
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Dieta Ocidental
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Fígado
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Camundongos Endogâmicos C57BL
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Obesidade
Limite:
Animals
Idioma:
En
Revista:
J Lipid Res
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos