Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters

Type 2 diabetes and other elements of the metabolic syndrome have increased at an alarming rate over the past several decades. There has been a parallel rise in the incidence [...]
Obesity is accompanied by chronic, low-grade inflammation of adipose tissue, which promotes insulin resistance and type-2 diabetes. These findings raise the question of how fat inflammation can escape the powerful armamentarium of cells and molecules normally responsible for guarding against a runaway immune response. [CD4.sup.+] [Foxp3.sup.+] T regulatory ([T.sub.reg]) cells with a unique phenotype were highly enriched in the abdominal fat of normal mice, but their numbers were strikingly and specifically reduced at this site in insulin-resistant models of obesity. Loss-of-function and gain-of-function experiments revealed that these [T.sub.reg] cells influenced the inflammatory state of adipose tissue and, thus, insulin resistance. Cytokines differentially synthesized by fat-resident regulatory and conventional T cells directly affected the synthesis of inflammatory mediators and glucose uptake by cultured adipocytes. These observations suggest that harnessing the anti-inflammatory properties of [T.sub.reg] cells to inhibit elements of the metabolic syndrome may have therapeutic potential.