Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14803
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Funding
- DFG
- CMMC
- CECAD
- CIHR (Canada)
- Max-Planck-Society (Germany)
- EMBO long-term fellowship
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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-alpha (IL-6R alpha(T-KO)) exposed to a HFD display improved glucose tolerance, insulin sensitivity and inflammation in liver and EWATafter 8 weeks. However, after 16 weeks, insulin resistance in IL-6R alpha(T-KO) epididymal white adipose tissue (EWAT) is comparable to that of controls, whereas the inflammatory profile is significantly worse. This coincided with a shift from classical T cell IL-6 signalling at 8 weeks, to enhanced IL-6 trans-signalling at 16 weeks. Collectively, our studies reveal that IL-6 action in T cells through classical IL-6 signalling promotes inflammation and insulin resistance early during obesity development, which can be compensated for by enhanced IL-6 trans-signalling at later stages.
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