In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 294, No. 2 ( 2008-02), p. E284-E290
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00601.2007
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1477331-4
SSG:
12
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