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Steroidogenic control of liver metabolism through a nuclear receptor-network.
- 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.)
- Subjects :
- Animals
Bile Acids and Salts metabolism
Glucose metabolism
HEK293 Cells
Hepatocytes metabolism
Homeostasis
Humans
Ketones metabolism
Lipogenesis
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Oxidation-Reduction
Receptors, Cytoplasmic and Nuclear
Signal Transduction
Steroid 17-alpha-Hydroxylase physiology
Liver metabolism
PPAR alpha metabolism
Steroid 17-alpha-Hydroxylase metabolism
Subjects
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