Sphingosine d18:1 promotes nonalcoholic steatohepatitis by inhibiting macrophage HIF-2α.
Nat Commun
; 15(1): 4755, 2024 Jun 04.
Article
en En
| MEDLINE
| ID: mdl-38834568
ABSTRACT
Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d181 [So(d181)] is selected from NASH patients. So(d181) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d181) promotes NASH and clarifies that So(d181) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esfingosina
/
Ratones Noqueados
/
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico
/
Enfermedad del Hígado Graso no Alcohólico
/
Macrófagos
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China