RESEARCH ARTICLE A Western-Fed Diet Increases Plasma HDL and LDL-Cholesterol Levels in ApoD–/– Mice

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 apoD2/2 mice on a C57BL/6 background after receiving a high fat-high cholesterol diet for 12 weeks. ApoD2/2 mice had higher HDL-cholesterol levels (61¡13-apoD2/2 vs. 52¡10-WT-males; 37¡11-apoD2/2 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 apoD2/2 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 apoD2/2 mice were not different, however