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| Status |
Public on Jan 28, 2018 |
| Title |
IL-10 signaling remodels adipose chromatin architecture to limit thermogenesis and energy expenditure [RNA-Seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| 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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| Contributor(s) |
Thomas BJ, Rajbhandari P |
| Citation(s) |
29249357 |
| Submission date |
Feb 08, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Peter Tontonoz |
| Organization name |
UCLA
|
| Department |
Pathology
|
| Lab |
Tontonoz Lab
|
| Street address |
675 Charles E Young
|
| City |
Los Angeles |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (11)
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| This SubSeries is part of SuperSeries: |
| GSE94654 |
IL-10 signaling remodels adipose chromatin architecture to limit thermogenesis and energy expenditure |
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| Relations |
| BioProject |
PRJNA371743 |
| SRA |
SRP099043 |
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