Unknown

Dataset Information

0

Netrin-1 promotes adipose tissue macrophage retention and insulin resistance in obesity.


ABSTRACT: 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.

SUBMITTER: Ramkhelawon B 

PROVIDER: S-EPMC3981930 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6699780 | BioStudies
2013-01-01 | S-EPMC3793633 | BioStudies
2007-01-01 | S-EPMC2587297 | BioStudies
1000-01-01 | S-EPMC1964510 | BioStudies
2017-01-01 | S-EPMC5516622 | BioStudies
2019-01-01 | S-EPMC6514622 | BioStudies
1000-01-01 | S-EPMC5873875 | BioStudies
2016-01-01 | S-EPMC5002490 | BioStudies
1000-01-01 | S-EPMC5651811 | BioStudies
2017-01-01 | S-EPMC5440033 | BioStudies