title: 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.affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Steinbacher
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pedicatrics, Paracelsus Medical University of Salzburg, Salzburg, Austria.
authors.forename: René G
authors.initials: RG
authors.lastname: Feichtinger
authors.affiliation: First Department of Internal Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria.
authors.forename: Lyudmyla
authors.initials: L
authors.lastname: Kedenko
authors.affiliation: First Department of Internal Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria.
authors.forename: Igor
authors.initials: I
authors.lastname: Kedenko
authors.affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.
authors.forename: Sandra
authors.initials: S
authors.lastname: Reinhardt
authors.affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Schönauer
authors.affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.
authors.forename: Isabella
authors.initials: I
authors.lastname: Leitner
authors.affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Sänger
authors.affiliation: Department of Cell Biology, Paris Lodron-University of Salzburg, Salzburg, Austria.
authors.forename: Walter
authors.initials: W
authors.lastname: Stoiber
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pedicatrics, Paracelsus Medical University of Salzburg, Salzburg, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
authors.affiliation: Medical Office in Pediatrics and Sports Medicine, Salzburg, Austria.
authors.forename: Holger
authors.initials: H
authors.lastname: Förster
authors.affiliation: First Department of Internal Medicine, Paracelsus Medical University of Salzburg, Salzburg, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Paulweber
authors.affiliation: Department of Sport Science and Kinesiology, Paris Lodron-University of Salzburg, Hallein, Austria.
authors.forename: Susanne
authors.initials: S
authors.lastname: Ring-Dimitriou
mesh_terms: D000328:Adult; D015444:Exercise / Q000502:physiology*; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010807:Physical Endurance / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D064326:MEF2 Transcription Factors; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors