Detrimental role for fat T_reg in insulin resistance

Age-associated insulin resistance (IR) and obesity-associated IR are physiologically distinct forms of adult-onset diabetes. Although macrophage-driven inflammation drives the obesity-associated condition, the mechanisms for age-associated IR are not known. Ronald Evans and colleagues show that fat-resident regulatory T cells (fT_regcells) accumulate in adipose tissue as a function of age, but not obesity. Mice lacking fT_reg cells are protected against age-associated IR, yet remain susceptible to obesity-associated IR and metabolic disease. Depletion of fT_reg cells via anti-ST2 antibody treatment increases adipose tissue insulin sensitivity. Although not the main topic of this study, these findings do not support a role for fT_reg cells in obesity-associated insulin resistance or in the therapeutic actions of thiazolidinedione or ‘glitazone’ antidiabetics. This contradicts claims that T_reg cells were beneficial and necessary for restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone.