Dataset Information

Steroidogenic Control of Liver Metabolism Through a Nuclear Receptor-Network

ABSTRACT: 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. 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, catalyses the production of a hormone-ligand (DHEA) for 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-signalling, involving the receptors FXR, SHP and LRH-1. Together, these findings represent a novel paradigm of homeostatic control in which nutritional cues feed-forward on to metabolic pathways by influencing extragonadal steroidogenesis.

INSTRUMENT(S): Orbitrap Fusion ETD

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Liver

SUBMITTER: Harmjan Vos

LAB HEAD: Bryn M Owen

PROVIDER: PXD012876 | Pride | 2020-01-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	20150109_F1_HRV_Alex_16FT.raw	Raw
	20150109_F1_HRV_Alex_16PH11.raw	Raw
	20150109_F1_HRV_Alex_16PH8.raw	Raw
	20150109_F1_HRV_Alex_16Ph2.raw	Raw
	20150109_F1_HRV_Alex_16Ph5.raw	Raw

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Publications

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

Milona Alexandra A Massafra Vittoria V Vos Harmjan H Naik Jyoti J Artigas Natalia N Paterson Helen A B HAB Bijsmans Ingrid T G W ITGW Willemsen Ellen C L ECL Ramos Pittol Jose M JM Miguel-Aliaga Irene I Bosma Piter P Burgering Boudewijn M T BMT Williamson Catherine C Vernia Santiago S Dhillo Waljit S WS van Mil Saskia W C SWC Owen Bryn M BM

Molecular metabolism 20190930

<h4>Objective</h4>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.<h4>Methods and results</h4>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, cata ...[more]

PMID: 31767173

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