title: The nuclear receptor DAF-12 regulates nutrient metabolism and reproductive growth in nematodes.
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.
authors.affiliation: Deparment of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stoltzfus
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: Young-Jai
authors.initials: YJ
authors.lastname: You
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Najju
authors.initials: N
authors.lastname: Ranjit
authors.affiliation: Department of Clinical Science, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: Hao
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Clinical Science, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Pathology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: James B
authors.initials: JB
authors.lastname: Lok
authors.affiliation: Deparment of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mangelsdorf
authors.affiliation: Deparment of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America; Department of Molecular Biology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Kliewer
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D015801:Helminth Proteins / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D017171:Strongyloides stercoralis / Q000254:growth & development* / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; D005227:Fatty Acids; D015801:Helminth Proteins; D018160:Receptors, Cytoplasmic and Nuclear