Reference - Detail
| 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 |
| WOS Category | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | News |
| Total number of mentions | 5 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1800 |