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Accession IconSRP099043

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

Organism Icon Mus musculus
Sample Icon 11 Downloadable Samples
Technology Badge IconIllumina HiSeq 4000, Illumina HiSeq 2000

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Description
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. Overall design: Immortalized brown/beige-like preadipocyte cell line(iBAd Cells) was used for ATAC-Seq and mRNA-Seq. For RNA-Seq, triplicate experiments were performed, for ATAC-Seq individual samples were sequenced after 5 days of differentiation with either control treatment, or including IL-10 overnight prior to addition of Isoproterenol for 5-6 hours. Inguinal White adipose tissue was used for RNA-Seq from either WT or IL-10-/- animals, where 11 IL10-/- mice and 9 WT mice were seperately pooled for library construction and sequencing.
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11
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