| First Author | Xu YX | Year | 2020 |
| Journal | iScience | Volume | 23 |
| Issue | 4 | Pages | 100973 |
| PubMed ID | 32213464 | Mgi Jnum | J:312845 |
| Mgi Id | MGI:6717484 | Doi | 10.1016/j.isci.2020.100973 |
| Citation | Xu YX, et al. (2020) EDEM3 Modulates Plasma Triglyceride Level through Its Regulation of LRP1 Expression. iScience 23(4):100973 |
| abstractText | Human genetics studies have uncovered genetic variants that can be used to guide biological research and prioritize molecular targets for therapeutic intervention for complex diseases. We have identified a missense variant (P746S) in EDEM3 associated with lower blood triglyceride (TG) levels in >300,000 individuals. Functional analyses in cell and mouse models show that EDEM3 deficiency strongly increased the uptake of very-low-density lipoprotein and thereby reduced the plasma TG level, as a result of up-regulated expression of LRP1 receptor. We demonstrate that EDEM3 deletion up-regulated the pathways for RNA and endoplasmic reticulum protein processing and transport, and consequently increased the cell surface mannose-containing glycoproteins, including LRP1. Metabolomics analyses reveal a cellular TG accumulation under EDEM3 deficiency, a profile consistent with individuals carrying EDEM3 P746S. Our study identifies EDEM3 as a regulator of blood TG, and targeted inhibition of EDEM3 may provide a complementary approach for lowering elevated blood TG concentrations. |
