| First Author | Ribas V | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 39 | Pages | 16457-62 |
| PubMed ID | 21900603 | Mgi Jnum | J:176674 |
| Mgi Id | MGI:5292425 | Doi | 10.1073/pnas.1104533108 |
| Citation | Ribas V, et al. (2011) Myeloid-specific estrogen receptor {alpha} deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development. Proc Natl Acad Sci U S A 108(39):16457-62 |
| abstractText | ERalpha is expressed in macrophages and other immune cells known to exert dramatic effects on glucose homeostasis. We investigated the impact of ERalpha expression on macrophage function to determine whether hematopoietic or myeloid-specific ERalpha deletion manifests obesity-induced insulin resistance in mice. Indeed, altered plasma adipokine and cytokine levels, glucose intolerance, insulin resistance, and increased adipose tissue mass were observed in animals harboring a hematopoietic or myeloid-specific deletion of ERalpha. A similar obese phenotype and increased atherosclerotic lesion area was displayed in LDL receptor-KO mice transplanted with ERalpha(-/-) bone marrow. In isolated macrophages, ERalpha was necessary for repression of inflammation, maintenance of oxidative metabolism, IL-4-mediated induction of alternative activation, full phagocytic capacity in response to LPS, and oxidized LDL-induced expression of ApoE and Abca1. Furthermore, we identified ERalpha as a direct regulator of macrophage transglutaminase 2 expression, a multifunctional atheroprotective enzyme. Our findings suggest that diminished ERalpha expression in hematopoietic/myeloid cells promotes aspects of the metabolic syndrome and accelerates atherosclerosis in female mice. |
