| First Author | Tuong ZK | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 1 | Pages | e0147179 |
| PubMed ID | 26812621 | Mgi Jnum | J:257390 |
| Mgi Id | MGI:6093053 | Doi | 10.1371/journal.pone.0147179 |
| Citation | Tuong ZK, et al. (2016) RORalpha and 25-Hydroxycholesterol Crosstalk Regulates Lipid Droplet Homeostasis in Macrophages. PLoS One 11(1):e0147179 |
| abstractText | Nuclear hormone receptors have important roles in the regulation of metabolic and inflammatory pathways. The retinoid-related orphan receptor alpha (Roralpha)-deficient staggerer (sg/sg) mice display several phenotypes indicative of aberrant lipid metabolism, including dyslipidemia, and increased susceptibility to atherosclerosis. In this study we demonstrate that macrophages from sg/sg mice have increased ability to accumulate lipids and accordingly exhibit larger lipid droplets (LD). We have previously shown that BMMs from sg/sg mice have significantly decreased expression of cholesterol 25-hydroxylase (Ch25h) mRNA, the enzyme that produces the oxysterol, 25-hydroxycholesterol (25HC), and now confirm this at the protein level. 25HC functions as an inverse agonist for RORalpha. siRNA knockdown of Ch25h in macrophages up-regulates Vldlr mRNA expression and causes increased accumulation of LDs. Treatment with physiological concentrations of 25HC in sg/sg macrophages restored lipid accumulation back to normal levels. Thus, 25HC and RORalpha signify a new pathway involved in the regulation of lipid homeostasis in macrophages, potentially via increased uptake of lipid which is suggested by mRNA expression changes in Vldlr and other related genes. |
