XXXX in @entity28 is associated with critical alterations in tregulatory cell numbers.

@entity1 @entity32 @entity6 @entity28 @entity19 @entity1759 @entity403 @entity9536 @entity2935 @entity9350 @entity366
BACKGROUND: The development of insulin resistance (IR) in @entity19 models of @entity28 and @entity6 ( @entity6 ) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue @entity32 via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose @entity32 and investigated the role of Tregs in IR/ @entity28 through coordinated studies in @entity19 and @entity1 . METHODS AND FINDINGS: @entity403 -green fluorescent protein (GFP) "knock-in" @entity19 were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese @entity1 without overt type 2 @entity6 (n=13) and lean controls (n=7) were recruited prospectively for assessment of @entity32 . DIO resulted in increased CD3(+)CD4(+), and CD3(+)CD8(+) cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with @entity9536 (+) @entity2935 (+) adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors @entity366 and @entity9350 and marker of activation @entity1759 . In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. @entity1 visceral adipose in morbid @entity28 was characterized by an increase in @entity2935 (+) ATMs and a decrease in @entity403 expression. CONCLUSIONS: Our experiments indicate that @entity28 in @entity19 and @entity1 results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose @entity32 .
