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Steroidogenic control of liver metabolism through a nuclear receptor-network.

Authors :
Milona A
Massafra V
Vos H
Naik J
Artigas N
Paterson HAB
Bijsmans ITGW
Willemsen ECL
Ramos Pittol JM
Miguel-Aliaga I
Bosma P
Burgering BMT
Williamson C
Vernia S
Dhillo WS
van Mil SWC
Owen BM
Source :
Molecular metabolism [Mol Metab] 2019 Dec; Vol. 30, pp. 221-229. Date of Electronic Publication: 2019 Sep 30.
Publication Year :
2019

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.<br />Methods and Results: 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 PPARĪ±, and is ultimately required for maintaining euglycemia and ketogenesis during nutrient deprivation. The feedback-loop that terminates Cyp17a1-PPARĪ± 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.<br />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.<br /> (Copyright © 2019 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Details

Language :
English
ISSN :
2212-8778
Volume :
30
Database :
MEDLINE
Journal :
Molecular metabolism
Publication Type :
Academic Journal
Accession number :
31767173
Full Text :
https://doi.org/10.1016/j.molmet.2019.09.007