論文 - 詳細
| RRC ID | 46073 |
|---|---|
| 著者 | Magner DB, Wollam J, Shen Y, Hoppe C, Li D, Latza C, Rottiers V, Hutter H, Antebi A. |
| タイトル | The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans. |
| ジャーナル | 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. |
| 巻・号 | 18(2) |
| ページ | 212-24 |
| 公開日 | 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 |
| 引用数 | 41 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm1800 |