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| Status |
Public on Oct 27, 2017 |
| Title |
Hepatic Expression of Ectodysplasin (ED) A Increases in Obesity and Impairs Insulin Sensitivity in Skeletal Muscle |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We screened intronic microRNAs dysregulated in liver of obese mouse models to identify previously uncharacterized coding host genes that may contribute to the pathogenesis of obesity-associated insulin resistance and type 2 diabetes mellitus. Our approach identified the expression of Ectodysplasin A (Eda), the causal gene of X-linked hypohidrotic ectodermal dysplasia (XLHED; MIM 305100) was strongly increased in liver of obese mouse models both in rodents and humans.Eda expression in murine liver is controlled via PPARγ activation, increases in circulation and promotes JNK activation and inhibitory serine phosphorylation of IRS1 in skeletal muscle. Consistently, bi-directional modulation of hepatic Eda expression in mouse models affects systemic glucose metabolism with alterations of muscle insulin signaling, revealing a novel role of EDA as an obesity-associated hepatokine, which impairs insulin sensitivity in skeletal muscle.
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| Overall design |
Soleus muscle mRNA profiles of db/db mice at 3 weeks after injection of AAV encoding shRNA targeting mouse Eda or the control scrambled shRNA sequence at the titer of 2-3x10e10 particles/body.
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| Contributor(s) |
Awazawa M, Gabel P, Tsaousidou E, Nolte H, Krüger M, Schmitz J, Ackermann PJ, Brandt C, Kornfeld J, Wunderlich FT, Blüher M, Brüning JC |
| Citation(s) |
29106399 |
| Submission date |
Jun 30, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Motoharu Awazawa |
| E-mail(s) |
motoharuawazawa@gmail.com
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| Phone |
+81-3-3202-7181
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| Organization name |
National Institute for Global Health and Medicine
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| Street address |
1-21-1 Toyama, Shinjuku
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| City |
Tokyo |
| ZIP/Postal code |
1638655 |
| Country |
Japan |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA392670 |
| SRA |
SRP110814 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE100686_shEda_muscle_FPKM.xls.gz |
2.4 Mb |
(ftp)(http) |
XLS |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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