| First Author | Ali K | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 12 | Pages | e115744 |
| PubMed ID | 25548917 | Mgi Jnum | J:225372 |
| Mgi Id | MGI:5693194 | Doi | 10.1371/journal.pone.0115744 |
| Citation | Ali K, et al. (2014) A Western-fed diet increases plasma HDL and LDL-cholesterol levels in apoD-/- mice. PLoS One 9(12):e115744 |
| abstractText | OBJECTIVE: Plasma apolipoprotein (apo)D, a ubiquitously expressed protein that binds small hydrophobic ligands, is found mainly on HDL particles. According to studies of human genetics and lipid disorders, plasma apoD levels positively correlate with HDL-cholesterol and apoAI levels. Thus, we tested the hypothesis that apoD was a regulator of HDL metabolism. METHODS & RESULTS: We compared the plasma lipid and lipoprotein profiles of wild-type (WT) C57BL/6 mice with apoD-/- mice on a C57BL/6 background after receiving a high fat-high cholesterol diet for 12 weeks. ApoD-/- mice had higher HDL-cholesterol levels (61+/-13-apoD-/- vs. 52+/-10-WT-males; 37+/-11-apoD-/- vs. 22+/-2 WT-female) than WT mice with sex-specific changes in total plasma levels of cholesterol and other lipids. Compared to WT, the HDL of apoD-/- mice showed an increase in large, lipid-rich HDL particles and according to size various quantities and sizes of LDL particles. Plasma levels of lecithin:cholesterol acyltransferase in the control and apoD-/- mice were not different, however, plasma phospholipid transfer protein activity was modestly elevated (+10%) only in male apoD-/- mice. An in vivo HDL metabolism experiment with isolated Western-fed apoD-/- HDL particles showed that female apoD-/- mice had a 36% decrease in the fractional catabolic rate of HDL cholesteryl ester. Hepatic SR-BI and LDLR protein levels were significantly decreased; accordingly, LDL-cholesterol and apoB levels were increased in female mice. CONCLUSION: In the context of a high fat-high cholesterol diet, apoD deficiency in female mice is associated with increases in both plasma HDL and LDL-cholesterol levels, reflecting changes in expression of SR-BI and LDL receptors, which may impact diet-induced atherosclerosis. |
