PPARGC1A Gly482Ser polymorphism is associated with elite endurance athletic status – endurance genes

The PPARGC1A gene Gly482Ser in Polish and Russian athletes.

Maciejewska A, Sawczuk M, Cieszczyk P, Mozhayskaya IA, Ahmetov II.

Source

Department of Genetics, University of Szczecin, Szczecin, Poland.

Abstract

Peroxysome proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α; encoded by the gene PPARGC1A in humans) is a crucial component in training-induced muscle adaptation because it is a co-activator of transcriptional factors that control gene expression in coordinated response to exercise. It has been suggested that a Gly482Ser substitution in PPARGC1A has functional relevance in the context of human disorders and athletic performance. To test this hypothesis, we examined the genotype distribution of PPARGC1A Gly482Ser in a group of Polish athletes and confirmed the results obtained in a replication study of Russian athletes. We found that the 482Ser allele was under-represented in the cohort of Polish and Russian athletes examined compared with unfit controls (P < 0.0001). A statistically significant low frequency of the 482Ser allele was observed among the endurance,strength-endurance, and sprint-strength groups of Polish athletes (P = 0.019, P = 0.022, and P < 0.0001, respectively). The replication study revealed that the 482Ser allele was also less prevalent in Russian endurance and strength-endurance athletes (P = 0.029 and P < 0.0001, respectively). Our results suggest that the PPARGC1A Gly482Ser polymorphism is associated with elite endurance athletic status. These findings support the hypothesis that the PPARGC1A 482Ser allele may impair aerobic capacity: thus, the Gly482 allele may be considered a beneficial factor for endurance performance.

PMID:

22122487

[PubMed – in process]

Skeletal Muscle-Specific Expression of PGC-1α-b, an Exercise-Responsive Isoform, Increases Exercise Capacity and Peak Oxygen Uptake

Abstract

BACKGROUND:

Maximal oxygen uptake (VO(2max)) predicts mortality and is associated with endurance performance. Trained subjects have a high VO(2max) due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO(2max). There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO(2max) and exercise capacity.

METHODOLOGY/PRINCIPAL FINDINGS:

Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed) by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice.

CONCLUSIONS/SIGNIFICANCE:

Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy for sedentary subjects to perform exercise efficiently, which would lead to prevention of life-style related diseases and increased lifespan.

FULL ARTICLE CAN BE READ HERE:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234261/pdf/pone.0028290.pdf

 

The effects of creatine and glycerol hyperhydration on running economy in well trained endurance runners

Ingestion of creatine (Cr) and glycerol (Gly) has been reported to be an effective method in expanding water compartments within the human body, attenuating the rise in heart rate (HR) and core temperature (Tcore) during exercise in the heat. Despite these positive effects, a substantial water retention could potentially impair endurance performance through increasing body mass (BM) and consequently impacting negatively on running economy (RE). The objective of the present study was to investigate the effects of a combined Cr and Gly supplementation on thermoregulatory and cardiovascular responses and RE during running for 30 min at speed corresponding to 60% of maximal oxygen uptake (VO2max) in hot and cool conditions. Methods: Cr * H2O (11.4 g), Gly (1 g * kg-1 BM) and Glucose polymer (75 g) were administered twice daily to 15 male endurance runners during a 7-day period. Exercise trials were conducted pre- and post-supplementation at 10 and 35 degreesC and 70% relative humidity. Results: BM and total body water increased by 0.90 +/- 0.40 kg (P < 0.01; mean +/- SD) and 0.71 +/- 0.42 L (P < 0.01), respectively following supplementation. Despite the significant increase in BM, supplementation had no effect on VO2 and therefore RE. Both HR and Tcore were attenuated significantly after supplementation (P < 0.05, for both). Nevertheless, thermal comfort and rating of perceived exertion was not significantly different between pre- and post-supplementation. Similarly, no significant differences were found in sweat loss, serum osmolality, blood lactate and in plasma volume changes between pre- and post-supplementation. Conclusions: Combining Cr and Gly is effective in reducing thermal and cardiovascular strain during exercise in the heat without negatively impacting on RE.

PGC-1α-b expression in muscle increases Exercise Capacity and Peak Oxygen Uptake

Abstract

BACKGROUND:

Maximal oxygen uptake (VO(2max)) predicts mortality and is associated with endurance performance. Trained subjects have a high VO(2max) due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO(2max). There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO(2max) and exercise capacity.

METHODOLOGY/PRINCIPAL FINDINGS:

Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed) by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice.

CONCLUSIONS/SIGNIFICANCE:

Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy for sedentary subjects to perform exercise efficiently, which would lead to prevention of life-style related diseases and increased lifespan.

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