Citation | Magner DB, Wollam J, Shen Y, Hoppe C, Li D, Latza C, Rottiers V, Hutter H, Antebi A. The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans. Cell Metab, 2013. |
PubMed ID | 23931753 |
Short Description | The NHR-8 nuclear receptor regulates cholesterol and bile acid homeostasis in C. elegans. GEO Record: GSE48675 Platform: GPL7727 Download gene-centric, log2 transformed data: WBPaper00044030.ce.mr.csv |
# of Conditions | 14 |
Full Description
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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. Experimental Details: WBPaper00044030:N2_rep1 WBPaper00044030:N2_rep2 WBPaper00044030:nhr-8(hd117)_rep1 WBPaper00044030:N2_rep3 WBPaper00044030:nhr-8(hd117)_rep2 WBPaper00044030:nhr-8(hd117)_rep3 WBPaper00044030:N2_rep4 WBPaper00044030:nhr-8(hd117)_rep4 WBPaper00044030:N2_rep5 WBPaper00044030:nhr-8(hd117)_rep5 WBPaper00044030:N2_rep6 WBPaper00044030:nhr-8(hd117)_rep6 WBPaper00044030:N2_rep7 WBPaper00044030:nhr-8(hd117)_rep7. |
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