Atherosclerotic lesion formation and triglyceride storage in obese apolipoprotein AI-deficient mice.
Obese leptin-deficient (ob/ob) mice have increased levels of high-density lipoprotein (HDL) and a unique lipoprotein referred to as low-density lipoprotein (LDL)/HDL1. When crossed onto an apolipoprotein AI (apoAI)-deficient (-/-) background, ob/ob;apoAI-/- mice accumulate LDL/HDL1 in the absence of traditional HDL. To determine the role of LDL/HDL1 in atherosclerosis, C57BL/6, apoAI-/-, ob/ob and ob/ob;apoAI-/- mice were placed on butterfat diet. After 20 weeks, all four groups had a significant increase in total cholesterol levels. The cholesterol in C57BL/6 mice was carried on very low-density lipoprotein (VLDL) and LDL and, in ob/ob and ob/ob;apoAI-/- mice, on HDL and LDL/HDL1. Atherosclerotic lesion area was similar among C57BL/6, ob/ob and ob/ob;apoAI-/- groups despite their dissimilar lipoprotein profiles. Hepatic triglyceride production and VLDL clearance rates were similar among the four groups. The ob/ob;apoAI-/- group had a significant decrease in liver weight and an increase in white adipose tissue (WAT) weight compared to the ob/ob group. Hepatic scavenger receptor class B type I (SR-BI) levels were decreased in both liver and WAT in ob/ob;apoAI-/- compared to ob/ob mice. Conclusions regarding the atherogenicity of LDL/HDL1 were confounded by the differences in lipoprotein profiles among the four groups. However, our studies provide support for the concept that apoAI and SR-BI assist in the partitioning of lipid from adipose tissue to the liver.
Plummer
Michelle R
MR
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Hasty
Alyssa H
AH
D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000502:physiology*; D050197:Atherosclerosis / Q000473:pathology*; D015153:Blotting, Western; D008066:Lipolysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism* / Q000473:pathology*; D009929:Organ Size; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism*
D016632:Apolipoprotein A-I; D014280:Triglycerides