While macrophage-dependent inflammation is the driver of obesity-associated insulin resistance, the mechanisms of age-associated insulin resistance remain unclear. In Nature, Zheng and colleagues show that fat resident Treg cells modulate age-associated insulin resistance in mice. Although the macrophage subsets remain unchanged, the Treg cell population expands substantially with age in the visceral adipose tissue (VAT). Selective depletion of Treg cells in the fat of aged mice leads to improved insulin sensitivity, remodeling of VAT, less hepatic steatosis, lower body mass, greater oxygen consumption and higher core body temperature, without systemic inflammation. VAT Treg cells have higher expression of Pparg, Gata3, Irf4, Ctla4, Il2ra and Il10 and of the IL-33 receptor ST2 than that of splenic Treg cells and maintain considerable suppressive ability in aged mice. Partial depletion of fat Treg cells by targeting ST2 enhances the insulin sensitivity of VAT without signs of systemic Treg cell dysfunction, which would suggest therapeutic potential.

Nature (18 November 2015) doi:10.1038/nature16151