Decrease in αβ/γT-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation

The implication of and T cells in obesity-associated inflammation and insulin resistance (IR) remains uncertain. Mice lacking T cells show either no difference or a decrease in high-fat diet (HFD)-induced IR, whereas partial depletion in T cells does not protect from HFD-induced IR. T-cell deficiency leads to a decrease in white adipose tissue (WAT) inflammation and IR without weight change, but partial depletion of these cells has not been studied. We previously described a mouse model overexpressing peroxisome proliferator-activated receptor (PPAR-) specifically in T cells [transgenic (Tg) T-PPAR-] that exhibits a partial depletion in T cells and no change in T-cell number. This results in a decreased / T-cell ratio in lymphoid organs. We now show that Tg T-PPAR- mice are partially protected against HFD-induced weight gain and exhibit decreased IR and liver steatosis independently of animal weight. These mice display an alteration of WAT-depots distribution with an increased epididymal-WAT mass and a decreased subcutaneous WAT mass. Immune cell number is decreased in both WAT-depots, except for T cells, which are increased in epididymal-WAT. Overall, we show that decreasing / T-cell ratio in WAT-depots alters their inflammatory state and mass repartition, which might be involved in improvement of insulin sensitivity.Le Menn, G., Sibille, B., Murdaca, J., Rousseau, A.-S., Squillace, R., Vergoni, B., Cormont, M., Niot, I., Grimaldi, P. A., Mothe-Satney, I., Neels, J. G. Decrease in / T-cell ratio is accompanied by a reduction in high-fat diet-induced weight gain, insulin resistance, and inflammation.