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| Status |
Public on Jul 24, 2020 |
| Title |
The Innate Immune Factor IRF3 Reduces Adipose Thermogenesis via ISG15-mediated Reprogramming of Cellular Metabolism |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Purpose: Interferon regulatory factor 3 (IRF3) is activated by pro-inflammatory cytokines, but its role in regulating adaptive thermogenesis and energy expenditure remains unclear. Here, we report that IRF3 as a negative transcription regulator of adaptive thermogenesis. Adipocyte-specific IRF3 knockout (FI3KO) attenuates HFD-induced obesity by increasing energy expenditure; further studies show that IRF3 suppresses adaptive thermogenesis through ISG15-mediated inhibition of glycolysis in adipocytes. Conversely, overexpression of IRF3 in adipocytes causes reduced thermogenesis gene expression, energy expenditure, and more persistent to HFD-induced obesity. Moreover, Isg15-/- increases adipose thermogenesis and protects mice from HFD-induced obesity and glucose intolerance. Taken together, these data indicate that IRF3 as a transcriptional regulator connecting between inflammatory signaling pathway and energy homeostasis
Methods: primary adipocyte mRNA profiles of 8-week-old wild-type (WT) and FI3OE mice were generated by deep sequencing. The sequence reads that passed quality filters were analyzed at the transcript isoform level. qRT–PCR validation was performed using RT-PCR.
Conclusions: Our study represents the first detailed analysis of adipocyte transcriptomes from WT and FI3OE iWAT, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that Irf3 adipocyte-speficic overrxpression markedly increases the expression of Isg15 and Herc6, which play important role in regulation of glycolysis.
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| Overall design |
primary adipocyte mRNA profiles of 8-week-old old wild type (WT) and FI3OE mice
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| Contributor(s) |
Yan S, Rosen E |
| Citation(s) |
33571167 |
| |
| Submission date |
Jul 23, 2020 |
| Last update date |
Oct 28, 2024 |
| Contact name |
NORC Boston |
| E-mail(s) |
fungen.core@gmail.com
|
| Organization name |
Beth Israel Deaconess Medical Center
|
| Street address |
3 Blackfan Circle, CLS0733
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA648157 |
| SRA |
SRP273336 |
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