Temporal and tissue-specific requirements for T-lymphocyte IL-6 signalling in obesity-associated inflammation and insulin resistance

Low-grade inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells. Interleukin-6 (IL-6) is a crucial regulator of T cells and is increased in obesity. Here we report that classical IL-6 signalling in T cells promotes inflammation and insulin resistance during the first 8 weeks on a high-fat diet (HFD), but becomes dispensable at later stages (after 16 weeks). Mice with T cell-specific deficiency of IL-6 receptor-α (IL-6RαT-KO) exposed to a HFD display improved glucose tolerance, insulin sensitivity and inflammation in liver and EWAT after 8 weeks. However, after 16 weeks, insulin resistance in IL-6RαT-KO epididymal white adipose tissue (EW…