| First Author | Gutierrez DA | Year | 2011 |
| Journal | Diabetes | Volume | 60 |
| Issue | 11 | Pages | 2820-9 |
| PubMed ID | 21926275 | Mgi Jnum | J:189485 |
| Mgi Id | MGI:5445865 | Doi | 10.2337/db11-0314 |
| Citation | Gutierrez DA, et al. (2011) Aberrant accumulation of undifferentiated myeloid cells in the adipose tissue of CCR2-deficient mice delays improvements in insulin sensitivity. Diabetes 60(11):2820-9 |
| abstractText | OBJECTIVE: Mice with CCR2 deficiency are protected from insulin resistance but only after long periods of high-fat diet (HFD) feeding, despite the virtual absence of circulating inflammatory monocytes. We performed a time course study in mice with hematopoietic and global CCR2 deficiency to determine adipose tissue-specific mechanisms for the delayed impact of CCR2 deficiency on insulin resistance. RESEARCH DESIGN AND METHODS: Mice with global or hematopoietic CCR2 deficiency (CCR2(-/-) and BM-CCR2(-/-), respectively) and wild-type controls (CCR2(+/+) and BM-CCR2(+/+), respectively) were placed on an HFD for 6, 12, and 20 weeks. Adipose tissue myeloid populations, degree of inflammation, glucose tolerance, and insulin sensitivity were assessed. RESULTS: Flow cytometry analysis showed that two different populations of F4/80(+) myeloid cells (CD11b(lo)F4/80(lo) and CD11b(hi)F4/80(hi)) accumulated in the adipose tissue of CCR2(-/-) and BM-CCR2(-/-) mice after 6 and 12 weeks of HFD feeding, whereas only the CD11b(hi)F4/80(hi) population was detected in the CCR2(+/+) and BM-CCR2(+/+) controls. After 20 weeks of HFD feeding, the CD11b(lo)F4/80(lo) cells were no longer present in the adipose tissue of CCR2(-/-) mice, and only then were improvements in adipose tissue inflammation detected. Gene expression and histological analysis of the CD11b(lo)F4/80(lo) cells indicated that they are a unique undifferentiated monocytic inflammatory population. The CD11b(lo)F4/80(lo) cells are transiently found in wild-type mice, but CCR2 deficiency leads to the aberrant accumulation of these cells in adipose tissue. CONCLUSIONS: The discovery of this novel adipose tissue monocytic cell population provides advances toward understanding the pleiotropic role of CCR2 in monocyte/macrophage accumulation and regulation of adipose tissue inflammation. |
