Research ArticleImmunometabolism

PI3Kγ activity in leukocytes promotes adipose tissue inflammation and early-onset insulin resistance during obesity

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Sci. Signal.  18 Jul 2017:
Vol. 10, Issue 488, eaaf2969
DOI: 10.1126/scisignal.aaf2969

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Dual modulator of macrophages

The kinase PI3Kγ is thought to inhibit classical macrophage activation, an effect that enables tumor progression. However, Breasson et al. found that PI3Kγ promoted the activation of macrophages in two different mouse models of obesity. Analysis of mice with whole-body or tissue-specific deficiencies in PI3Kγ revealed that PI3Kγ in a nonhematopoietic cell type regulated adiposity but that PI3Kγ in leukocytes was required for the recruitment of neutrophils to adipose tissue, which was associated with macrophage activation and inflammation. Thus, PI3Kγ can either inhibit or stimulate macrophages depending on the pathophysiological context.