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| Status |
Public on Jul 25, 2023 |
| Title |
NFIA in adipocytes reciprocally regulates mitochondrial and inflammatory gene program to improve glucose homeostasis [ChIP-seq] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Adipose tissue is central to regulation of systemic energy homeostasis. Adaptive thermogenesis in brown and beige adipocytes, which relies on mitochondrial oxidative phosphorylation, dissipates energy to counteract obesity. On the other hand, chronic inflammation in adipose tissue is linked to insulin resistance, type 2 diabetes and obesity. Here we show that nuclear factor I-A (NFIA), a transcriptional regulator of brown and beige adipocytes, improves systemic glucose homeostasis via up-regulation of oxidative phosphorylation and reciprocal down-regulation of inflammation. Mice with transgenic expression of NFIA in adipocytes exhibited improved glucose tolerance, increased energy expenditure and limited weight gain on high fat diet. NFIA coordinately up-regulate genes involved in oxidative phosphorylation as well as a battery of brown-fat-specific genes through enhancer activation that involves facilitated genomic binding of PPARγ. In contrast, NFIA in adipocytes, but not in macrophages, down-regulate pro-inflammatory cytokine genes to ameliorate adipose tissue inflammation in vivo. NFIA binds to enhancer/promoter region of Ccl2 gene that encodes pro-inflammatory cytokine MCP-1, to down-regulate its transcription. NFIA expression and CCL2 expression was negatively correlated in human adipose tissue. These results indicate that NFIA in adipocytes reciprocally regulate mitochondrial and inflammatory gene program to improve systemic glucose homeostasis.
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| Overall design |
ChIP-seq analysis of WT and NFIA-Tg adipocytes
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| Contributor(s) |
Hiraike Y, Saito K, Oguchi M, Tsutsumi S, Aburatani H, Waki H, Yamauchi T |
| Citation(s) |
37487068 |
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| Submission date |
Apr 05, 2022 |
| Last update date |
Jul 26, 2023 |
| Contact name |
Yuta Hiraike |
| E-mail(s) |
hiraike-tky@umin.net
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| Organization name |
The University of Tokyo
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| Street address |
Hongo 7-3-1, Bunkyo-ku
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| City |
Tokyo |
| ZIP/Postal code |
1130033 |
| Country |
Japan |
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| Platforms (1) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE200194 |
NFIA in adipocytes reciprocally regulates mitochondrial and inflammatory gene program to improve glucose homeostasis |
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| Relations |
| BioProject |
PRJNA823656 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE200192_RAW.tar |
1.2 Gb |
(http)(custom) |
TAR (of BIGWIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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