 |
 |
GEO help: Mouse over screen elements for information. |
|
| 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 |
| E-mail(s) |
xingxingkong@mednet.ucla.edu
|
| Organization name |
UCLA
|
| Street address |
UCLA PEDIATRICS, 10833 LE CONTE AVE, CHS-MARION DAVIES CHILDREN CTR
|
| City |
LOS ANGELES |
| State/province |
CA |
| ZIP/Postal code |
90095 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
|
| Samples (6)
|
|
| Relations |
| BioProject |
PRJNA562888 |
| SRA |
SRP219832 |
| 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 |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...