Pluto Bioinformatics

GSE99068 (mouse): IL-6/Stat3-Dependent Induction of Distinct, Obesity-Associated Natural Killer Cells Deteriorates Energy and Glucose Homeostasis

Bulk RNA sequencing

Natural killer (NK) cells contribute to the development of obesity-associated insulin resistance. We demonstrate that in mice obesity promotes the expansion of interleukin-6 receptor (IL6Ra)-expressing NK cells, which also express a number of other myeloid lineage genes such as the colony-stimulating-factor 1 receptor (Csf1r). Selective ablation of Csf1r- expressing NK cells prevents obesity and insulin resistance. Moreover, conditional inactivation of IL6Ra or Stat3 in NK cells limits obesity-associated formation of myeloid signature NK cells, protects from obesity, insulin resistance and obesity-associated inflammation. Also in humans IL6Ra+ NK cells increase in obesity, correlate with markers of systemic low-grade inflammation and their gene expression profile overlaps with characteristic gene sets of NK cells in obese mice. Collectively, we demonstrate that obesity-associated inflammation and metabolic disturbances depend on IL-6/Stat3-dependent formation of distinct NK cells, which may provide a novel target for the treatment of obesity, metaflammation-associated pathologies and diabetes. SOURCE: Sebastian Theurich (sebastian.theurich@uk-koeln.de) - Neuronal Control of Metabolism (Brüning Lab) Max-Planck-Institute for Metabolism Research and University Hospital of Cologne

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