| First Author | Ramkhelawon B | Year | 2014 |
| Journal | Nat Med | Volume | 20 |
| Issue | 4 | Pages | 377-84 |
| PubMed ID | 24584118 | Mgi Jnum | J:210258 |
| Mgi Id | MGI:5569872 | Doi | 10.1038/nm.3467 |
| Citation | Ramkhelawon B, et al. (2014) Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity. Nat Med 20(4):377-84 |
| abstractText | During obesity, macrophage accumulation in adipose tissue propagates the chronic inflammation and insulin resistance associated with type 2 diabetes. The factors, however, that regulate the accrual of macrophages in adipose tissue are not well understood. Here we show that the neuroimmune guidance cue netrin-1 is highly expressed in obese but not lean adipose tissue of humans and mice, where it directs the retention of macrophages. Netrin-1, whose expression is induced in macrophages by the saturated fatty acid palmitate, acts via its receptor Unc5b to block their migration. In a mouse model of diet-induced obesity, we show that adipose tissue macrophages exhibit reduced migratory capacity, which can be restored by blocking netrin-1. Furthermore, hematopoietic deletion of Ntn1 facilitates adipose tissue macrophage emigration, reduces inflammation and improves insulin sensitivity. Collectively, these findings identify netrin-1 as a macrophage retention signal in adipose tissue during obesity that promotes chronic inflammation and insulin resistance. |
