Transcriptomics,Multiomics

Dataset Information

5

Transcription profiling of mouse skeletal muscle overexpressing PPARalpha


ABSTRACT: This experiment was conducted to identify target genes of the peroxisome proliferator-activated receptor alpha (PPARa) in skeletal muscle of transgenic mice that overexpressed PPARa. The following abstract from the published manuscript describes the major findings of this work. A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes.Finck BN, Bernal-Mizrachi C, Han DH, Coleman T, Sambandam N, LaRiviere LL, Holloszy JO, Semenkovich CF, Kelly DP. The role of the peroxisome proliferator-activated receptor-alpha (PPARalpha) in the development of insulin-resistant diabetes was evaluated using gain- and loss-of-function approaches. Transgenic mice overexpressing PPARalpha in muscle (MCK-PPARalpha mice) developed glucose intolerance despite being protected from diet-induced obesity. Conversely, PPARalpha null mice were protected from diet-induced insulin resistance in the context of obesity. In skeletal muscle, MCK-PPARalpha mice exhibited increased fatty acid oxidation rates, diminished AMP-activated protein kinase activity, and reduced insulin-stimulated glucose uptake without alterations in the phosphorylation status of key insulin-signaling proteins. These effects on muscle glucose uptake involved transcriptional repression of the GLUT4 gene. Pharmacologic inhibition of fatty acid oxidation or mitochondrial respiratory coupling prevented the effects of PPARalpha on GLUT4 expression and glucose homeostasis. These results identify PPARalpha-driven alterations in muscle fatty acid oxidation and energetics as a potential link between obesity and the development of glucose intolerance and insulin resistance. Experiment Overall Design: RNA from two wild-type (non-transgenic (NTG)) and two PPARalpha overexpressing (MCK-PPARa) mice was analyzed. Two replicates of each are provided.

OTHER RELATED OMICS DATASETS IN: PRJNA97127

ORGANISM(S): Mus musculus  

SUBMITTER: Brian Finck 

PROVIDER: E-GEOD-5777 | ArrayExpress | 2008-06-14

SECONDARY ACCESSION(S): GDS2289GSE5777PRJNA97127

REPOSITORIES: GEO, ArrayExpress

Dataset's files

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Action DRS
E-GEOD-5777.README.txt Txt
E-GEOD-5777.idf.txt Idf
E-GEOD-5777.processed.1.zip Processed
E-GEOD-5777.sdrf.txt Txt
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Publications

A potential link between muscle peroxisome proliferator- activated receptor-alpha signaling and obesity-related diabetes.

Finck Brian N BN   Bernal-Mizrachi Carlos C   Han Dong Ho DH   Coleman Trey T   Sambandam Nandakumar N   LaRiviere Lori L LL   Holloszy John O JO   Semenkovich Clay F CF   Kelly Daniel P DP  

Cell metabolism 20050201 2


The role of the peroxisome proliferator-activated receptor-alpha (PPARalpha) in the development of insulin-resistant diabetes was evaluated using gain- and loss-of-function approaches. Transgenic mice overexpressing PPARalpha in muscle (MCK-PPARalpha mice) developed glucose intolerance despite being protected from diet-induced obesity. Conversely, PPARalpha null mice were protected from diet-induced insulin resistance in the context of obesity. In skeletal muscle, MCK-PPARalpha mice exhibited in  ...[more]

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