Mice deficient in apolipoprotein E but not LDL receptors are resistant to accelerated atherosclerosis associated with obesity.
The aims of this study were to determine whether mice induced to become obese also exhibited accelerated atherosclerosis, and to determine whether obesity itself or dyslipidemia associated with obesity enhanced atherosclerosis. Wild-type (C57BL/6) mice and mice deficient for the low density lipoprotein receptor (LDLR-/-) or apolipoprotein E (apoE-/-) were fed a low fat, rodent chow diet or a high fat, high sucrose (diabetogenic) diet to induce obesity. As compared with wild-type mice, diabetogenic diet-fed LDLR-/- mice became more obese and developed severe dyslipidemia. Consequently, atherosclerotic lesions were increased in the LDLR-/- mice 3.7-fold over chow fed values. ApoE-/- mice showed weight gain profiles similar to those observed for wild-type mice. However, no differences in plasma lipid levels, lipoprotein profiles or atherosclerotic lesion areas were observed between chow-fed and diabetogenic diet-fed apoE-/- mice. These data demonstrate that lipid storage and partitioning as mediated by the low density lipoproteins (LDL) receptor or apoE-/- have profound and opposing consequences for dyslipidemia and atherosclerosis susceptibility associated with obesity.
Schreyer
Sandra A
SA
Department of Cell Biology and Biochemistry, AstraZeneca, Mölndal, Sweden.
Lystig
Theodore C
TC
Vick
Cynthia M
CM
LeBoeuf
Renée C
RC
D000818:Animals; D001055:Apolipoproteins B / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000097:blood / Q000172:deficiency* / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003324:Coronary Artery Disease / Q000276:immunology* / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006949:Hyperlipidemias / Q000209:etiology / Q000378:metabolism; D007113:Immunity, Innate; D008075:Lipoproteins, HDL / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000187:drug effects / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000187:drug effects / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008955:Models, Cardiovascular; D009765:Obesity / Q000276:immunology* / Q000378:metabolism*; D011237:Predictive Value of Tests; D011973:Receptors, LDL / Q000097:blood / Q000172:deficiency* / Q000187:drug effects; D013223:Statistics as Topic; D014280:Triglycerides / Q000378:metabolism
D001055:Apolipoproteins B; D001057:Apolipoproteins E; D015415:Biomarkers; D004041:Dietary Fats; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides