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Series GSE72462 Query DataSets for GSE72462
Status Public on Jun 29, 2016
Title TGFβ contributes to impaired exercise response by suppression of mitochondrial key regulators in skeletal muscle
Organism Homo sapiens
Experiment type Expression profiling by array
Summary substantial number of people at risk to develop type 2 diabetes could not improve insulin sensitivity by physical training intervention. We studied the mechanisms of this impaired exercise response in 20 middle-aged individuals who performed a controlled eight weeks cycling and walking training at 80 % individual VO2max. Participants identified as non-responders in insulin sensitivity (based on Matsuda index) did not differ in pre-intervention parameters compared to high responders. The failure to increase insulin sensitivity after training correlates with impaired up-regulation of mitochondrial fuel oxidation genes in skeletal muscle, and with the suppression of the upstream regulators PGC1α and AMPKα2. The muscle transcriptome of the non-responders is further characterized by an activation of TGFβ and TGFβ target genes, which is associated with increases in inflammatory and macrophage markers. TGFβ1 as inhibitor of mitochondrial regulators and insulin signaling is validated in human skeletal muscle cells. Activated TGFβ1 signaling down-regulates the abundance of PGC1α, AMPKα2, mitochondrial transcription factor TFAM, and of mitochondrial enzymes. Thus, increased TGFβ activity in skeletal muscle can attenuate the improvement of mitochondrial fuel oxidation after training and contribute to the failure to increase insulin sensitivity.
Overall design We performed gene expression microarray analysis on muscle biopsies from humans before and after an eight weeks endurance training intervention
Contributor(s) Böhm A, Hoffmann C, Irmler M, Schneeweiss P, Schnauder G, Sailer C, Schmid V, Hudemann J, Machann J, Schick F, Beckers J, Hrabĕ de Angelis M, Staiger H, Fritsche A, Stefan N, Nieß A, Häring H, Weigert C
Citation(s) 27358493
Submission date Aug 27, 2015
Last update date Mar 01, 2019
Contact name Johannes Beckers
Organization name Helmholtz Zentrum Muenchen
Department Institute of Experimental Genetics
Street address Ingolstaedter Landstr. 1
City Neuherberg
ZIP/Postal code 85764
Country Germany
Platforms (1)
GPL17586 [HTA-2_0] Affymetrix Human Transcriptome Array 2.0 [transcript (gene) version]
Samples (36)
GSM1862914 Baseline_rep2
GSM1862915 Baseline_rep3
GSM1862916 Baseline_rep4
BioProject PRJNA294095

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Supplementary file Size Download File type/resource
GSE72462_RAW.tar 810.6 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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