IL-10 Signaling Remodels Adipose Chromatin Architecture to Limit Thermogenesis and Energy Expenditure

Prashant Rajbhandari, Brandon J. Thomas, An Chieh Feng, Cynthia Hong, Jiexin Wang, Laurent Vergnes, Tamer Sallam, Bo Wang, Jaspreet Sandhu, Marcus M. Seldin, Aldons J. Lusis, Loren G. Fong, Melanie Katz, Richard Lee, Stephen G. Young, Karen Reue, Stephen T. Smale, Peter Tontonoz

Research output: Contribution to journalArticlepeer-review

Abstract

Signaling pathways that promote adipose tissue thermogenesis are well characterized, but the 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 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 differentiation, obesity, and aging. Assay for transposase-accessible chromatin sequencing (ATAC-seq), ChIP-seq, and RNA-seq reveal that IL-10 represses the transcription of thermogenic genes in adipocytes by altering chromatin accessibility and inhibiting ATF and C/EBPβ recruitment to key enhancer regions. These findings expand our understanding of the relationship between inflammatory signaling pathways and adipose tissue function and provide insight into the physiological control of thermogenesis that could inform future therapy. An anti-inflammatory cytokine suppresses adipocyte thermogenesis to limit energy expenditure.

Original languageEnglish (US)
Pages (from-to)218-233.e17
JournalCell
Volume172
Issue number1-2
DOIs
StatePublished - Jan 11 2018
Externally publishedYes

Keywords

  • adipogenesis
  • IL-10
  • immunometabolism
  • thermogenesis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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