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

The implication of αβ and γδ T cells in obesity‐associated inflammation and insulin resistance (IR) remains uncertain. Mice lacking γδ T cells show either no difference or a decrease in high‐fat diet (HFD)‐induced IR, whereas partial depletion in γδ T cells does not protect from HFD‐induced IR. αβ 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 β (PPAR‐β) specifically in T cells [transgenic (Tg) T–PPAR‐β] that exhibits a partial depletion in αβ T cells and no change in γδ T‐cell number. This results in a decreased αβ/γδ T‐cell ratio in lymphoid organs. We now show that Tg T–PPAR‐β 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 γδ T cells, which are increased in epididymal‐WAT. Overall, we show that decreasing αβ/γδ 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 αβ/γδ T‐cell ratio is accompanied by a reduction in high‐fat diet‐induced weight gain, insulin resistance, and inflammation. FASEB J. 33, 2553–2562 (2019). www.fasebj.org