Steroidogenic control of liver metabolism through a nuclear receptor-network.
Mol Metab
; 30: 221-229, 2019 12.
Article
em 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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Esteroide 17-alfa-Hidroxilase
/
PPAR alfa
/
Fígado
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article