Phospholipid transfer protein deficiency ameliorates diet-induced hypercholesterolemia and inflammation in mice.
Phospholipid transfer protein (PLTP) facilitates the transfer of phospholipids from triglyceride-rich lipoproteins into HDL. PLTP has been shown to be an important factor in lipoprotein metabolism and atherogenesis. Here, we report that chronic high-fat, high-cholesterol diet feeding markedly increased plasma cholesterol levels in C57BL/6 mice. PLTP deficiency attenuated diet-induced hypercholesterolemia by dramatically reducing apolipoprotein E-rich lipoproteins (-88%) and, to a lesser extent, LDL (-40%) and HDL (-35%). Increased biliary cholesterol secretion, indicated by increased hepatic ABCG5/ABCG8 gene expression, and decreased intestinal cholesterol absorption may contribute to the lower plasma cholesterol in PLTP-deficient mice. The expression of proinflammatory genes (intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) is reduced in aorta of PLTP knockout mice compared with wild-type mice fed either a chow or a high-cholesterol diet. Furthermore, plasma interleukin-6 levels are significantly lower in PLTP-deficient mice, indicating reduced systemic inflammation. These data suggest that PLTP appears to play a proatherogenic role in diet-induced hyperlipidemic mice.
Shelly
Lorraine
L
Department of Cardiovascular, Metabolic, & Endocrine Diseases, Pfizer Global Research Division, Pfizer, Inc., Groton, CT 06340, USA.
Royer
Lori
L
Sand
Thomas
T
Jensen
Heather
H
Luo
Yi
Y
D000821:Animal Feed; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005838:Genotype; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049294:Phospholipid Transfer Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; D008055:Lipids; D049294:Phospholipid Transfer Proteins; D018799:Intercellular Adhesion Molecule-1