ILRUN , a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice
| العنوان: | ILRUN , a Human Plasma Lipid GWAS Locus, Regulates Lipoprotein Metabolism in Mice |
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| المؤلفون: | Raymond E. Soccio, Nicholas J. Hand, Yachen Shen, John S. Millar, Paul C. Lee, Li Li, Takashi Kuwano, Xin Bi, Daniel J. Rader |
| المصدر: | Circulation Research. 127:1347-1361 |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, biology, Physiology, Cholesterol, Regulator, Locus (genetics), Inflammation, Genome-wide association study, Metabolism, Cell biology, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, Ubiquitin, medicine, biology.protein, medicine.symptom, Cardiology and Cardiovascular Medicine, Gene, 030217 neurology & neurosurgery |
| الوصف: | Rationale: Single-nucleotide polymorphisms near the ILRUN (inflammation and lipid regulator with ubiquitin-associated–like and NBR1 [next to BRCA1 gene 1 protein]-like domains) gene are genome-wide significantly associated with plasma lipid traits and coronary artery disease (CAD), but the biological basis of this association is unknown. Objective: To investigate the role of ILRUN in plasma lipid and lipoprotein metabolism. Methods and Results: ILRUN encodes a protein that contains a ubiquitin-associated–like domain, suggesting that it may interact with ubiquitinylated proteins. We generated mice globally deficient for Ilrun and found they had significantly lower plasma cholesterol levels resulting from reduced liver lipoprotein production. Liver transcriptome analysis uncovered altered transcription of genes downstream of lipid-related transcription factors, particularly PPARα (peroxisome proliferator-activated receptor alpha), and livers from Ilrun -deficient mice had increased PPARα protein. Human ILRUN was shown to bind to ubiquitinylated proteins including PPARα, and the ubiquitin-associated–like domain of ILRUN was found to be required for its interaction with PPARα. Conclusions: These findings establish ILRUN as a novel regulator of lipid metabolism that promotes hepatic lipoprotein production. Our results also provide functional evidence that ILRUN may be the casual gene underlying the observed genetic associations with plasma lipids at 6p21 in human. |
| تدمد: | 1524-4571 0009-7330 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::7294127a22aa214dfc9cced7bb3ae2ad https://doi.org/10.1161/circresaha.120.317175 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........7294127a22aa214dfc9cced7bb3ae2ad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244571 00097330 |
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