| First Author | Li P | Year | 2013 |
| Journal | Cell | Volume | 155 |
| Issue | 1 | Pages | 200-214 |
| PubMed ID | 24074869 | Mgi Jnum | J:205151 |
| Mgi Id | MGI:5544159 | Doi | 10.1016/j.cell.2013.08.054 |
| Citation | Li P, et al. (2013) NCoR repression of LXRs restricts macrophage biosynthesis of insulin-sensitizing omega 3 fatty acids. Cell 155(1):200-14 |
| abstractText | Macrophage-mediated inflammation is a major contributor to obesity-associated insulin resistance. The corepressor NCoR interacts with inflammatory pathway genes in macrophages, suggesting that its removal would result in increased activity of inflammatory responses. Surprisingly, we find that macrophage-specific deletion of NCoR instead results in an anti-inflammatory phenotype along with robust systemic insulin sensitization in obese mice. We present evidence that derepression of LXRs contributes to this paradoxical anti-inflammatory phenotype by causing increased expression of genes that direct biosynthesis of palmitoleic acid and omega3 fatty acids. Remarkably, the increased omega3 fatty acid levels primarily inhibit NF-kappaB-dependent inflammatory responses by uncoupling NF-kappaB binding and enhancer/promoter histone acetylation from subsequent steps required for proinflammatory gene activation. This provides a mechanism for the in vivo anti-inflammatory insulin-sensitive phenotype observed in mice with macrophage-specific deletion of NCoR. Therapeutic methods to harness this mechanism could lead to a new approach to insulin-sensitizing therapies. |
