Hepatic-specific activation of peroxisome proliferator-activated receptor γ coactivator-1ß protects against steatohepatitis.
Hepatology
; 57(4): 1343-56, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23299802
ABSTRACT
Development of hepatic steatosis and its progression to steatohepatitis may be the consequence of dysfunction of several metabolic pathways, such as triglyceride synthesis, very low-density lipoprotein (VLDL) secretion, and fatty acid ß-oxidation. Peroxisome proliferator-activated receptor γ coactivator-1ß (PGC-1ß) is a master regulator of mitochondrial biogenesis and oxidative metabolism, lipogenesis, and triglyceride (TG) secretion. Here we generated a novel mouse model with constitutive hepatic activation of PGC-1ß and studied the role of this transcriptional coactivator in dietary-induced steatosis and steatohepatitis. Selective activation of PGC-1ß within hepatocytes is able to protect the liver from lipid overload and from progression to fibrosis. The protective function exerted by PGC-1ß is due to its ability to induce mitochondrial oxidative phosphorylation, fatty acid ß-oxidation, and citrate cycle, as well as to decrease oxidative stress and promote TG secretion in the blood stream. These findings bolster the concept that a combined hepatic specific action of PGC-1ß on lipid synthesis and secretion, as well as on mitochondrial biogenesis and function, could protect against steatohepatitis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transativadores
/
Fígado Gorduroso
/
Fígado
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Hepatology
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Itália