Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the physiologic limiters of energy expenditure are largely unknown.  Here we show that ablation of the anti-inflammatory cytokine IL-10 improves insulin sensitivity, protects against diet-induced obesity, and elicits the browning of white adipose tissue.  Mechanistic studies define bone marrow cells as the source of the IL-10 signal and mature adipocytes as the target cell type mediating these effects.  IL-10 receptor alpha is highly enriched in mature adipocytes and is induced in response to cold, obesity and aging.  ATAC-seq and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and PGC-1alpha recruitment to key enhancer regions.  These findings identify the IL-10 axis as a critical and potentially targetable regulator of thermogenesis, and expand our understanding of the links between inflammatory signaling and adipose tissue function in the setting of obesity. SOURCE: Peter TontonozTontonoz Lab UCLA

Pluto Bioinformatics

GSE94653: IL-10 signaling remodels adipose chromatin architecture to limit thermogenesis and energy expenditure [RNA-Seq]