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The PPARa gene polymorphism in team sports athletes

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Peroxisome proliferator-activated receptor α (PPARα) is a transcription factor that regulates lipid and glucose metabolism. Accumulating evidence suggests that the intron 7 C allele of the PPARA gene rs4253778 G/C polymorphism has an advantage for power-oriented athletes, presumably due to the hypertrophic effects on skeletal muscle and increase in glucose utilization in response to anaerobic exercise. The G allele, however, is said to be favorable for the endurance-oriented athletes. The metabolic demands of team sports involve aerobic and anaerobic energy pathways, as a result of the intermittent physical activity. The aim of the present study was to investigate the association between the PPARA gene polymorphism and team-sport athletic status. A total of 665 Russian athletes from 14 team sports and 1,706 controls were involved in the case-control study. We found that the frequency of the PPARA C allele was significantly higher in athletes compared to controls (20.5 vs. 16.4%, P = 0.0009), suggesting that anaerobic rather than aerobic metabolism may be crucial to the game performance in team sports. This means that our study indicates the association between the PPARA gene G/C polymorphism and team-sport athletic status. Although more replication studies are needed, the preliminary data suggest an opportunity to use the analysis of PPARA polymorphism, along with other gene variations and standard phenotypic assessment in team sports selection.
Peroxisome proliferator-activated receptor alpha (PPAR) plays a crucial role in the transcriptional regulation of myocardial lipid metabolism. In vitro studies on isolated cardiomyocytes showed that PPAR activation induces expression of numerous genes involved in virtually all steps of fatty acid catabolism. However, there is very few data on the effect of PPAR activation on the content and composition of myocardial lipids in vivo. Therefore, our main aim was to examine effects of selective PPAR agonist WY-14643 on the content and fatty acid composition of major lipid classes in the heart of rats fed a standard chow (STD) or a high-fat diet (HFD). In STD rats WY-14643 paradoxically decreased palmitate oxidation rate in the heart, however, in HFD animals such effect was not observed. WY-14643 markedly reduced myocardial free fatty acid and diacylglycerol content in STD rats, whereas in HFD group the opposite effect was observed. These changes reflected alterations in plasma lipid concentration which suggests that effects of WY-14643 on the heart were indirect and secondary to changes in plasma lipid availability induced by the drug. Basal myocardial glucose uptake was not affected by PPAR agonist in either group, however, glycogen content in the heart was markedly increased. WY-14643 exerted profound influence on the fatty acid composition of myocardial phospholipids in both diet groups. These changes included increased percentage of monounsaturated fatty acids and replacement of n-3 polyunsaturated fatty acids (PUFA) by those from the n-6 family. This action of WY-14643 might be detrimental to the heart since n-3 PUFA possess cardioprotective and antiarrhythmic properties.
The elite athletic phenotype is a complex combination influenced by both multiple genes (polygenic) and environmental factors such as training and nutrition. Among single nucleotide polymorphisms (SNPs) associated with variation in physical traits, which are particularly important for performance in a variety of sports and with the elite athlete status, variants of PPAR (Peroxisome Proliferator-Activated Receptor) genes have emerged as crucial moderators that control the expression of genes encoding enzymes and other proteins involved in energy homeostasis (lipid and carbohydrate metabolism). Accumulated findings from studies showing that combinations of polymorphic markers located in PPAR genes are associated with increased/decreased performance raise the possibility that the PPAR gene variants are true performance enhancing polymorphisms (PEPs) that are believed to have a physiological impact on human body composition and metabolism. The aim of this review is to summarize the state of knowledge on the role of polymorphic variants of PPAR genes in physical performance or health related fitness phenotypes.
It was shown that high-fat feeding of mice with cardiac-specific overexpression of peroxisome proliferator-activated receptor (PPAR) alpha but not wild type animals leads to the accumulation of ceramide (an important mediator of lipotoxicity) in the heart [Finck et al. 2003 Proc Natl Acad Sci USA]. To investigate the mechanism of this phenomenon we examined the effects of PPARalpha activation on ceramide metabolism in the myocardium. Male Wistar rats were fed either a standard chow or a high-fat diet. Each group was divided into two subgroups: control and treated with selective PPARalpha activator – WY-14643. In the rats fed on the standard diet WY-14643 did not affect the myocardial content of sphingomyelin and ceramide but reduced the content of sphinganine and sphingosine. It also inhibited the activity of neutral sphingomyelinase and increased the activity of acid sphingomyelinase, whereas the activity of ceramidases and serine palmitoyltransferase (SPT) remained stable. High-fat diet itself did not affect the content of the examined sphingolipids. However, it reduced the activity of sphingomyelinases and ceramidases having no effect on the activity of SPT. Administration of WY-14643 to this group significantly increased the content of myocardial free palmitate, ceramide, sphingomyelin and the activity of SPT. Our results demonstrated that PPARalpha activation modulates myocardial ceramide metabolism and leads to the accumulation of ceramide in the heart of the high-fat fed rats due to its increased synthesis de novo.
Cardiac hypertrophy in humans is associated with a decrease in myocardial fatty acid β-oxidation (FAO) and accompanying alterations in metabolic gene expression. Flux through the cardiac FAO pathway, which is the principal source of energy production in the adult mammalian heart, is tightly controlled in accordance with energy demands. In rodents, the FAO pathway is under control of a nuclear peroxisome proliferator-activated receptor α (PPARα). We sought to delineate the molecular regulatory events involved in the energy substrate preference switch from fatty acids to glucose during cardiac hypertrophic growth in humans. We analysed the amount of PPARα protein in human cardiac tissue. PPARα protein level was measured in homogenates prepared from left ventricular biopsies taken from five control donor hearts and compared to the amount of this transcription factor in biopsies from five patients with compensated end-stage heart failure (HF) at the time of transplantation. Using Western blot analysis with a monoclonal antibody against human PPARα, we observed a significant decrease (54%) in the mean amount of PPARα in the group of HF patients compared to that in the donor tissue. This study indicates that the decrease in cardiac PPARα transcription factor gene expression observed in the failing human heart could play an important role in a reduction in fatty acid utilisation by the adult heart during cardiac hypertrophy.
The aim of this study was to investigate the effect of peroxisome proliferator activated receptors alpha agonist, fenofibrate, on the level of oxidative stress, total antioxidant capacity, and plasma paraoxonase 1 (PON1) activity in the rat. The adult male Wistar rats received fenofibrate for 7 days. The drug was added to food at concentrations 0.005%, 0.05% and 0.5%, which corresponded to doses of 3, 30 and 300 mg/kg/day, respectively. Fenofibrate treatment dose-dependently reduced plasma concentration of malonyldialdehyde and 4-hydroxydialkenals. The level of these lipid peroxidation products in animals treated with 0.005%, 0.05% and 0.5% fenofibrate was lower than in control group by 52.8%, 62.7% and 87.1%, respectively. Lipid hydroperoxides in plasma decreased by 29.7%, 23.4% and 27.5% in these groups, respectively. The drug had no significant effect on total antioxidant capacity measured as ferric reducing ability of plasma (FRAP). Paraoxon-hydrolyzing activity (PON) of plasma paraoxonase was 81.5% lower in animals receiving 0.05% fenofibrate and 69.2% lower in rats treated with 0.5% fenofibrate than in control. Phenyl acetate hydrolyzing activity (arylesterase, AE) was reduced by 15.2%, 49.6% and 55.8% in rats receiving 0.005%, 0.05% and 0.5% fenofibrate, respectively. PON/AE ratio decreased following 0.05% and 0.5% fenofibrate by 64.9% and 30.4%, respectively. The drug had no significant effect on total plasma triglycerides and cholesterol concentrations. The results indicate that fenofibrate treatment favourably modulates oxidant-antioxidant balance and unfavourably affects plasma PON1 activity in normolipidemic rats. These effects can contribute to the influence of PPARalpha agonists on pathological processes involved in atherogenesis.
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