Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates nonalcoholic fatty liver disease.
Can J Physiol Pharmacol
; 96(6): 587-596, 2018 Jun.
Article
en En
| MEDLINE
| ID: mdl-29406832
ABSTRACT
Nonalcoholic fatty liver disease (NAFLD) is often associated with obesity and type 2 diabetes. Coagonists of glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) are under clinical investigation for the treatment of obesity and type 2 diabetes. In this study, we have demonstrated the effect of a balanced coagonist in the treatment of NAFLD using mouse models. GLP-1R agonist exendin-4, glucagon, and coagonist (Aib2 C24 chimera2) were administered to C57BL6/J mice, in which NAFLD was induced by carbon tetrachloride (CCl4) treatment after high-fat diet (HFD) feeding, and choline-deficient, L-amino-acid-defined HFD (CDAHFD) feeding. Repeated dose administration of coagonist significantly attenuated liver inflammation and steatosis induced by acute and long-term treatment with CCl4 in HFD-fed mice. Coagonist markedly attenuated the CDAHFD-induced expression of TIMP-1, MMP-9, TNF-α, MCP-1, COL1A1, and α-SMA. It also inhibited progression of hepatic steatosis and fibrosis in mice. Exendin-4 was better than glucagon, but coagonist was most effective in reduction of hepatic inflammation as well as steatosis. Coagonist of GLP-1R and GCGR improved NAFLD in C57BL6/J mice. This effect is mediated by reduction in lipotoxicity and inflammation in liver.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Péptidos
/
Ponzoñas
/
Glucagón
/
Receptores de Glucagón
/
Péptido 1 Similar al Glucagón
/
Enfermedad del Hígado Graso no Alcohólico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Can J Physiol Pharmacol
Año:
2018
Tipo del documento:
Article
País de afiliación:
India