Steroidogenic control of liver metabolism through a nuclear receptor-network.
Mol Metab
; 30: 221-229, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31767173
ABSTRACT
OBJECTIVE:
Coupling metabolic and reproductive pathways is essential for the survival of species. However, the functions of steroidogenic enzymes expressed in metabolic tissues are largely unknown. METHODS ANDRESULTS:
Here, we show that in the liver, the classical steroidogenic enzyme Cyp17a1 forms an essential nexus for glucose and ketone metabolism during feed-fast cycles. Both gain- and loss-of-function approaches are used to show that hepatic Cyp17a1 is induced by fasting, catalyzes the production of at least one hormone-ligand (DHEA) for the nuclear receptor PPARα, and is ultimately required for maintaining euglycemia and ketogenesis during nutrient deprivation. The feedback-loop that terminates Cyp17a1-PPARα activity, and re-establishes anabolic liver metabolism during re-feeding is mapped to postprandial bile acid-signaling, involving the receptors FXR, SHP and LRH-1.CONCLUSIONS:
Together, these findings represent a novel paradigm of homeostatic control in which nutritional cues feed-forward on to metabolic pathways by influencing extragonadal steroidogenesis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Esteroide 17-alfa-Hidroxilasa
/
PPAR alfa
/
Hígado
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Mol Metab
Año:
2019
Tipo del documento:
Article
País de afiliación:
Reino Unido