RRC ID 46073
Author Magner DB, Wollam J, Shen Y, Hoppe C, Li D, Latza C, Rottiers V, Hutter H, Antebi A.
Title The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans.
Journal Cell Metab
Abstract Hormone-gated nuclear receptors (NRs) are conserved transcriptional regulators of metabolism, reproduction, and homeostasis. Here we show that C. elegans NHR-8 NR, a homolog of vertebrate liver X and vitamin D receptors, regulates nematode cholesterol balance, fatty acid desaturation, apolipoprotein production, and bile acid metabolism. Loss of nhr-8 results in a deficiency in bile acid-like steroids, called the dafachronic acids, which regulate the related DAF-12/NR, thus controlling entry into the long-lived dauer stage through cholesterol availability. Cholesterol supplementation rescues various nhr-8 phenotypes, including developmental arrest, unsaturated fatty acid deficiency, reduced fertility, and shortened life span. Notably, nhr-8 also interacts with daf-16/FOXO to regulate steady-state cholesterol levels and is synthetically lethal in combination with insulin signaling mutants that promote unregulated growth. Our studies provide important insights into nuclear receptor control of cholesterol balance and metabolism and their impact on development, reproduction, and aging in the context of larger endocrine networks.
Volume 18(2)
Pages 212-24
Published 2013-8-6
DOI 10.1016/j.cmet.2013.07.007
PII S1550-4131(13)00296-9
PMID 23931753
PMC PMC3909615
MeSH Amino Acid Sequence Animals Apolipoproteins / biosynthesis Bile Acids and Salts / metabolism* Biological Transport Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Cholestenes / metabolism Cholesterol / metabolism* Fatty Acids / metabolism Fertility / genetics Forkhead Transcription Factors Gene Expression Regulation Homeostasis Lipid Metabolism / genetics* Longevity / genetics Molecular Sequence Data Oxygenases / metabolism Receptors, Cytoplasmic and Nuclear / metabolism* Sequence Alignment Signal Transduction / genetics Transcription Factors / metabolism
IF 21.567
Times Cited 41
C.elegans tm1800