The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes

PLoS Genetics
Zhu WangSteven A Kliewer

Abstract

Appropriate nutrient response is essential for growth and reproduction. Under favorable nutrient conditions, the C. elegans nuclear receptor DAF-12 is activated by dafachronic acids, hormones that commit larvae to reproductive growth. Here, we report that in addition to its well-studied role in controlling developmental gene expression, the DAF-12 endocrine system governs expression of a gene network that stimulates the aerobic catabolism of fatty acids. Thus, activation of the DAF-12 transcriptome coordinately mobilizes energy stores to permit reproductive growth. DAF-12 regulation of this metabolic gene network is conserved in the human parasite, Strongyloides stercoralis, and inhibition of specific steps in this network blocks reproductive growth in both of the nematodes. Our study provides a molecular understanding for metabolic adaptation of nematodes to their environment, and suggests a new therapeutic strategy for treating parasitic diseases.

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Citations

Sep 19, 2015·Critical Reviews in Biochemistry and Molecular Biology·Julia Marianne Hoffmann, Linda Partridge
Mar 30, 2019·PLoS Pathogens·Alex Dulovic, Adrian Streit
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May 19, 2019·Current Opinion in Chemical Biology·Rebecca A Butcher

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Datasets Mentioned

BETA
E-MTAB-1164

Methods Mentioned

BETA
immunoprecipitation
electrophoresis
Biosensor
fluorescence microscopy
RNA-seq

Software Mentioned

Image
Significance Analysis of Microarrays ( SAM )
R package samr
Affymetrix
DAVID
TBLASTN

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