Hedgehog signaling is a potent regulator of liver lipid metabolism and reveals a GLI-code associated with steatosis.
Elife
; 52016 05 17.
Article
en En
| MEDLINE
| ID: mdl-27185526
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in industrialized countries and is increasing in prevalence. The pathomechanisms, however, are poorly understood. This study assessed the unexpected role of the Hedgehog pathway in adult liver lipid metabolism. Using transgenic mice with conditional hepatocyte-specific deletion of Smoothened in adult mice, we showed that hepatocellular inhibition of Hedgehog signaling leads to steatosis by altering the abundance of the transcription factors GLI1 and GLI3. This steatotic 'Gli-code' caused the modulation of a complex network of lipogenic transcription factors and enzymes, including SREBP1 and PNPLA3, as demonstrated by microarray analysis and siRNA experiments and could be confirmed in other steatotic mouse models as well as in steatotic human livers. Conversely, activation of the Hedgehog pathway reversed the "Gli-code" and mitigated hepatic steatosis. Collectively, our results reveal that dysfunctions in the Hedgehog pathway play an important role in hepatic steatosis and beyond.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Factores de Transcripción de Tipo Kruppel
/
Metabolismo de los Lípidos
/
Enfermedad del Hígado Graso no Alcohólico
/
Proteína con Dedos de Zinc GLI1
/
Receptor Smoothened
/
Hígado
/
Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Elife
Año:
2016
Tipo del documento:
Article
País de afiliación:
Alemania