Suppressing alarmins

Nat. Metab. https://doi.org/10.1038/s42255-018-0001-z (2018)

Increasing evidence shows that the immune system senses diet-derived signals that then influence metabolic responses. In Nature Metabolism, Fishman and colleagues report a link between nutrient-induced glucose-dependent insulinotropic polypeptide (GIP) signaling and the suppression of myeloid cell inflammatory responses. Mice that lack expression of the GIP receptor specifically in myeloid cells exhibit excessive weight gain, impaired glucose tolerance and dysregulation of cold-induced adaptive thermogenesis when fed a high-fat diet. Lack of the GIP receptor leads to increased expression of the alarmin S100A8 by fat-resident myeloid cells. This scenario leads to greater myelopoiesis, neutrophilia and recruitment of myeloid cells to fat depots than that of wild-type mice. This phenotype is ‘rescued’ by deficiency in S100A9, which stabilizes S100A8 protein and hence leads to functional double deficiency in the alarmins. The findings show a role for GIP signaling in myeloid cells in the maintenance of insulin sensitivity and thermogenesis in adipose tissues.