Effect of exercise on skeletal muscle metabolism mediated by PGC-1alpha and PPARdelta in non-diabetic males

Endurance exercise is often prescribed to improve cardiorespiratory fitness and metabolic flexibility in subjects predisposed to type 2 diabetes mellitus. Recently, single nucleotide polymorphisms (SNPs) in peroxisome proliferator-activated receptor (PPAR) and a co-activator of PPAR have been postulated to affect the magnitude of an exercise training on markers of physical fitness, insulin sensitivity and blood lipids, myofibrillar structure, and mitochondrial oxidative capacity. Because only retrospective data are available, we will test the hypothesis that non-diabetic males (45-65 yrs) with vs. without risk alleles differ in the magnitude of the training response after a 10-wks lasting cycling training equalling at least 1600 kcal/wk. The investigation of mechanism affecting exercise trainability is important for a more precise tailoring of exercise programs (“exercise is medicine concept”) targeted to improve cardiorespiratory fitness in subjects with normal or impaired glucose regulation. Based on power analysis for the main outcome variable (VO2peak) at least 90 males (45-65 yrs) will be recruited from the SAPHIR-sample after genotyping. A preliminary genotyping for SNPs in PGC-1 (Gly482Ser, rs8192678) and PPAR(rs2267668) of blood samples from male SAPHIR-participants has been conducted by the method as described in the following. Physical fitness, as cardiorespiratory fitness, respiratory thresholds, lactate turn points will be assessed by gas exchange measurements and amperometric analysis of ear-lobe blood before, during and after a graded cycle ergometer test to exhaustion. Fasting blood will be sampled from the antecubital vein to assess fasting blood glucose, HbA1c, fasting insulin and blood lipids. Muscle samples will be taken from the m. vastus lateralis of the non-dominant leg. The tissue will be further analysed for gene expression, mitochondria volume/density and mitochondria oxidative capacity, and intramuscular lipid concentration. All tests will be executed before and after 10 weeks of exercise intervention. The exercise interventions consists of 3-4 x 60min weekly cycling (stationary, Precor, ULSZ-Rif) at different heart rate levels equalling different respiratory thresholds (VT, AT and RCP) to improve VO2peak and anaerobic threshold. The proposed study aims are to investigate the possible impact of single-nucleotide polymorphisms in the PPARdelta and PGC-1alpha gene on the exercise-induced training response of parameters characterizing the “macro-level”, as physical fitness and clinical parameters, as well of parameters characterizing the “micro-level”, such as myocellular structure and mitochondria function.