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Series GSE136623 Query DataSets for GSE136623
Status Public on Aug 30, 2019
Title Metabolic regulation of BCAAs and glycogen via IRF4 in skeletal muscle
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Skeletal muscle is not only a primary site for glucose uptake and storage, but also a reservoir for amino acids stored as protein. How the metabolism of these two fuels is coordinated in skeletal muscle is incompletely understood. Here, we demonstrate that interferon regulatory factor 4 (IRF4) integrate glucose and amino acids flux by regulating glycogen synthesis and branched-chain-amino acid (BCAA) metabolism in skeletal muscle. Mice with IRF4 specifically knocked out in skeletal muscle (MI4KO) showed elevated plasma BCAAs and skeletal muscle glycogen content, decreased adiposity and body weight, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet-induced obesity (DIO). Loss of IRF4 caused downregulation of the mitochondrial branched-chain aminotransferase isozyme (BCATm) in myocytes, which encodes for the enzyme catalyzing the first step of BCAA metabolism. Lack of IRF4 also led to the upregulation of protein targeting to glycogen (PTG), which is associated with enhanced mitochondrial Complex II activity and mitochondria number. Additionally, overexpression of IRF4 in skeletal muscle caused obesity and reduced exercise capacity. Mechanistically, we found that IRF4 directly regulates both BCATm and PTG expression, and that overexpression of BCATm can partially reverse the effects of IRF4 deletion. These studies establish IRF4 as a novel driver of both glucose and BCAA metabolism in skeletal muscle.
Overall design Examination of different gene expression in skeletal muscle of muscle-specific IRF4 knockout mice and muscle-specific IRF4 overexpression mice.
Contributor(s) Kong X, Liu T
Citation(s) 33042761
Submission date Aug 29, 2019
Last update date Oct 22, 2020
Contact name Xingxing Kong
Organization name UCLA
State/province CA
ZIP/Postal code 90095
Country USA
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (6)
GSM4053154 MKO1283
GSM4053155 MKO1420
GSM4053156 MKO1421
BioProject PRJNA562888
SRA SRP219832

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE136623_MOE_vs_MKO_all_genes.txt.gz 1.2 Mb (ftp)(http) TXT
GSE136623_MOE_vs_MKO_at_fc_1.5_p_.05_872_genes.txt.gz 74.4 Kb (ftp)(http) TXT
GSE136623_RAW.tar 5.8 Mb (http)(custom) TAR (of TXT)
GSE136623_rsem_count.txt.gz 301.0 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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