Format

Send to

Choose Destination
Cell. 2018 Jan 11;172(1-2):218-233.e17. doi: 10.1016/j.cell.2017.11.019. Epub 2017 Dec 14.

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

Author information

1
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
2
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
3
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
4
Department of Medicine, Division of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
5
Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
6
Ionis Pharmaceuticals, Carlsbad, CA 92008, USA.
7
Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
8
Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
9
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA; Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: ptontonoz@mednet.ucla.edu.

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.

KEYWORDS:

IL-10; adipogenesis; immunometabolism; thermogenesis

PMID:
29249357
PMCID:
PMC5766418
[Available on 2019-01-11]
DOI:
10.1016/j.cell.2017.11.019

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center