The single nucleotide polymorphism Gly482Ser in the PGC-1α gene impairs exercise-induced slow-twitch muscle fibre transformation in humans.

Abstract

PGC-1α (peroxisome proliferator-activated receptor γ co-activator 1α) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1α gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1α in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation.

• Authors: Peter Steinbacher, René G Feichtinger, Lyudmyla Kedenko, Igor Kedenko, Sandra Reinhardt, Anna-Lena Schönauer, Isabella Leitner, Alexandra M Sänger, Walter Stoiber, Barbara Kofler, Holger Förster, Bernhard Paulweber, Susanne Ring-Dimitriou
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0123881 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25886402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MEF2 Transcription Factors
• PPARGC1A protein, human
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Transcription Factors

Topics

• Adult
• Exercise (physiology)
• Humans
• MEF2 Transcription Factors (genetics, metabolism)
• Male
• Muscle Fibers, Slow-Twitch (metabolism)
• Muscle, Skeletal (metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Physical Endurance (physiology)
• Polymorphism, Single Nucleotide
• Transcription Factors (genetics, metabolism)