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E-GEOD-29055 - Microarray skeletal muscle PPARbeta overexpressing mice

Status
Released on 12 December 2011, last updated on 26 June 2012
Organism
Mus musculus
Samples (4)
Array (1)
Protocols (6)
Description
This experiment was conducted to identify target genes of the peroxisome proliferator-activated receptor beta (PPARb) in skeletal muscle of transgenic mice that overexpressed PPARb. The following abstract from the submitted manuscript describes the major findings of this work. The Nuclear Receptor Transcription Factor PPARbeta/delta Programs Muscle Glucose Metabolism. Zhenji Gan, Eileen Burkart-Hartman, Dong-Ho Han, Brian Finck, Teresa C. Leone, John Holloszy, and Daniel P. Kelly. To identify new gene regulatory pathways controlling skeletal muscle energy metabolism, comparative studies were conducted on muscle-specific transgenic mouse lines expressing the nuclear receptors, PPARalpha (MCK-PPARalpha) or PPARbeta/delta (MCK-PPARbeta/delta). MCK-PPARbeta/delta mice are known to have enhanced exercise performance whereas MCK-PPARalpha mice perform at low levels. Transcriptional profiling revealed that the lactate dehydrogenase (Ldh)b/Ldha gene expression ratio is increased in MCK-PPARbeta/delta muscle, an isoenzyme shift that diverts pyruvate into the mitochondrion for the final steps of glucose oxidation. PPARbeta/delta gain- and loss-of-function studies in skeletal myotubes demonstrated that PPARbeta/delta, but not PPARalpha, interacts with the exercise inducible kinase, AMP-activated protein kinase (AMPK), to synergistically activate Ldhb gene transcription by cooperating with myocyte enhancer factor 2A (MEF2A), in a PPARbeta/delta ligand-independent manner. MCK-PPARbeta/delta muscle was shown to have high glycogen stores, increased levels of GLUT4, and augmented capacity for mitochondrial pyruvate oxidation suggesting a broad reprogramming of glucose utilization pathways. Lastly, exercise studies demonstrated that MCK-PPARbeta/delta mice had lower circulating levels of lactate compared to non-transgenic controls, while exhibiting supranormal performance on a high intensity exercise regimen. These results identify a transcriptional regulatory mechanism that increases capacity for muscle glucose utilization in a pattern that resembles the effects of exercise training. Keywords: muscle, exercise, nuclear receptors, glucose metabolism, gene regulation RNA from two wild-type (non-transgenic (NTG)) and two PPARbeta overexpressing (MCK-PPARb) mice was analyzed. Two replicates of each are provided.
Experiment type
transcription profiling by array 
Contacts
Daniel P Kelly, Eileen Burkart-Hartman, Zhenji Gan
Citation
The nuclear receptor PPARβ/δ programs muscle glucose metabolism in cooperation with AMPK and MEF2. Gan Z, Burkart-Hartman EM, Han DH, Finck B, Leone TC, Smith EY, Ayala JE, Holloszy J, Kelly DP. , PMID:22135324
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-29055.idf.txt
Sample and data relationshipE-GEOD-29055.sdrf.txt
Raw data (1)E-GEOD-29055.raw.1.zip
Processed data (1)E-GEOD-29055.processed.1.zip
Array designA-AFFY-36.adf.txt
R ExpressionSetE-GEOD-29055.eSet.r
Links