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This Article Full Text Full Text (PDF) All Versions of this Article: 294/2/E284    most recent 00601.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Atkinson, R. D. Articles by Hasty, A. H. PubMed PubMed Citation Articles by Atkinson, R. D. Articles by Hasty, A. H.

Macrophage-derived apolipoprotein E ameliorates dyslipidemia and atherosclerosis in obese apolipoprotein E-deficient mice

Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee

Submitted 14 September 2007 ; accepted in final form 20 November 2007

Previous studies have demonstrated that macrophage-derived apolipoprotein E (apoE) reduces atherosclerotic lesion formation in lean apoE-deficient (^–/–) mice. apoE has also been demonstrated to play a role in adipocyte differentiation and lipid accumulation. Because the prevalence of obesity has grown to epidemic proportions, we sought to determine whether macrophage-derived apoE could impact atherosclerotic lesion formation or adipose tissue expansion and inflammation in obese apoE^–/– mice. To this end, we transplanted obese leptin-deficient (ob/ob) apoE^–/– mice with bone marrow from either ob/ob;apoE^–/– or ob/ob;apoE^+/+ donors. There were no differences in body weight, total body adipose tissue, or visceral fat pad mass between recipient groups. The presence of macrophage-apoE had no impact on adipose tissue macrophage content or inflammatory cytokine expression. Recipients of apoE^+/+ marrow demonstrated 3.7-fold lower plasma cholesterol (P < 0.001) and 1.7-fold lower plasma triglyceride levels (P < 0.01) by 12 wk after transplantation even though apoE was present in plasma at concentrations <10% of wild-type levels. The reduced plasma lipids reflected a dramatic decrease in very low density lipoprotein and a mild increase in high-density lipoprotein levels. Atherosclerotic lesion area was >10-fold lower in recipients of ob/ob;apoE^+/+ marrow (P < 0.005). Similar results were seen in leptin receptor-deficient (db/db) apoE^–/– mice. Finally, when bone marrow transplantation was performed in 4-mo-old ob/ob;apoE^–/– and db/db;apoE^–/– mice with preexisting lesions, recipients of apoE^+/+ marrow had a 2.8-fold lower lesion area than controls (P = 0.0002). These results demonstrate that macrophage-derived apoE does not impact adipose tissue expansion or inflammatory status; however, even very low levels of macrophage-derived apoE are capable of reducing plasma lipids and atherosclerotic lesion area in obese mice.

obesity; very low-density lipoproteins; hyperlipidemia; atherosclerotic lesions