Genetic variations associated with non- contact muscle injuries in sport: A systematic review

Introduction Non-contact muscle injuries (NCMI) account for a large proportion of sport injuries, affecting athletes’ performance and career, team results and financial aspects. Recently, genetic factors have been attributed a role in the susceptibility of an athlete to sustain NCMI. However, data in this field are only just starting to emerge. Objectives To review available knowledge of genetic variations associated with sport-related NCMI. Methods The databases Pubmed, Scopus, and Web of Science were searched for relevant articles published until February 2021. The records selected for review were original articles published in peer-reviewed journals describing studies that have examined NCMI-related genetic variations in adult subjects (17–60 years) practicing any sport. The data extracted from the studies identified were as follows: general information, and data on genetic polymorphisms and NCMI risk, incidence and recovery time and/or severity. Results Seventeen studies examining 47 genes and 59 polymorphisms were finally included. 29 polymorphisms affecting 25 genes were found significantly associated with NCMI risk, incidence, recovery time, and/or severity. These genes pertain to three functional categories: (i) muscle fiber structural/contractile properties, (ii) muscle repair and regeneration, or (iii) muscle fiber external matrix composition and maintenance. Conclusion Our review confirmed the important role of genetics in NCMI. Some gene variants have practical implications such as differences of several weeks in recovery time detected between genotypes. Knowledge in this field is still in its early stages. Future studies need to examine a wider diversity of sports and standardize their methods and outcome measure

Mitochondrial uncoupling proteins regulate angiotensin-converting enzyme expression: crosstalk between cellular and endocrine metabolic regulators suggested by RNA interference and genetic studies.

Uncoupling proteins (UCPs) regulate mitochondrial function, and thus cellular metabolism. Angiotensin-converting enzyme (ACE) is the central component of endocrine and local tissue renin-angiotensin systems (RAS), which also regulate diverse aspects of whole-body metabolism and mitochondrial function (partly through altering mitochondrial UCP expression). We show that ACE expression also appears to be regulated by mitochondrial UCPs. In genetic analysis of two unrelated populations (healthy young UK men and Scandinavian diabetic patients) serum ACE (sACE) activity was significantly higher amongst UCP3-55C (rather than T) and UCP2 I (rather than D) allele carriers. RNA interference against UCP2 in human umbilical vein endothelial cells reduced UCP2 mRNA sixfold (P < 0·01) whilst increasing ACE expression within a physiological range (<1·8-fold at 48 h; P < 0·01). Our findings suggest novel hypotheses. Firstly, cellular feedback regulation may occur between UCPs and ACE. Secondly, cellular UCP regulation of sACE suggests a novel means of crosstalk between (and mutual regulation of) cellular and endocrine metabolism. This might partly explain the reduced risk of developing diabetes and metabolic syndrome with RAS antagonists and offer insight into the origins of cardiovascular disease in which UCPs and ACE both play a role

Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in energy metabolism revisited

Uncoupling protein 3 and physical activity: the role of uncoupling protein 3 in energy metabolism revisited. Schrauwen P, Hesselink M. Nutrition and Toxicology Research Institute Maastricht, Department of Human Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. [email protected] Physical activity influences energy metabolism in human subjects by increasing activity-induced energy expenditure and resting metabolic rate for several hours after exercise. On the other hand, physical activity increases mechanical energy efficiency, suggesting that trained subjects would need less energy for daily activities. The underlying mechanism by which physical activity influences energy metabolism is largely unknown. The skeletal muscle-specific homologue of uncoupling protein (UCP) 1, UCP3, could possibly play a major role in energy expenditure. UCP3 is, like UCP1, able to uncouple respiration from ATP production. A strong link or association between the UCP3 gene and energy metabolism was found. Furthermore, UCP3 mRNA expression is related to sleeping metabolic rate, and thyroid hormone, a powerful stimulator of energy expenditure, up regulates UCP3. Finally, mice overexpressing UCP3 are hyperphagic but lean. These findings indicated that UCP3 is related to energy metabolism and that UCP3 could have a role in the effect of physical activity on energy expenditure. Thus, acute exercise up regulates UCP3, whereas endurance training results in the down-regulation of UCP3 protein content. Only a minimal amount of physical activity is needed for down-regulation of UCP3. Moreover, there is very strong evidence that UCP3 is negatively related to mechanical energy efficiency, suggesting that the down-regulation of UCP3 with training increases mechanical energy efficiency. Taken together, although the exact function of UCP3 is still unknown, exercise and training studies clearly show that under certain circumstances UCP3 is strongly related to human energy metabolism, possibly as a secondary effect of its (yet) unknown primary function

Genetics and sports performance: the present and future in the identification of talent for sports based on DNA testing.

The impact of genetics on physiology and sports performance is one of the most debated research aspects in sports sciences. Nearly 200 genetic polymorphisms have been found to influence sports performance traits, and over 20 polymorphisms may condition the status of the elite athlete. However, with the current evidence, it is certainly too early a stage to determine how to use genotyping as a tool for predicting exercise/sports performance or improving current methods of training. Research on this topic presents methodological limitations such as the lack of measurement of valid exercise performance phenotypes that make the study results difficult to interpret. Additionally, many studies present an insufficient cohort of athletes, or their classification as elite is dubious, which may introduce expectancy effects. Finally, the assessment of a progressively higher number of polymorphisms in the studies and the introduction of new analysis tools, such as the total genotype score (TGS) and genome-wide association studies (GWAS), have produced a considerable advance in the power of the analyses and a change from the study of single variants to determine pathways and systems associated with performance. The purpose of the present study was to comprehensively review evidence on the impact of genetics on endurance- and power-based exercise performance to clearly determine the potential utility of genotyping for detecting sports talent, enhancing training, or preventing exercise-related injuries, and to present an overview of recent research that has attempted to correct the methodological issues found in previous investigations.post-print1358 K

Una variante del gen CAPN10 y los factores ambientales muestran asociación con el exceso de peso en jóvenes colombianos

ABSTRACT: Obesity results from interaction between genetic and environmental risk factors. Objective: To evaluate the effect of three gene variants and environmental factors on obesity and overweight in young people aged 10 to 18 years in a Colombian population. Materials and methods: A total of 424 subjects were selected and separated into three groups for a cross-sectional study; 100 obese and 112 overweight subjects were matched with 212 normal-weight controls. Associations were evaluated between excess weight and three genetic polymorphisms (UCP3- rs1800849, FTO-rs17817449, and CAPN10-rs3842570), as well as the family history, the time spent watching television and playing video games, and the diet. Results: A family history of obesity, the time spent watching television and playing video games, the lack of breastfeeding, a low consumption of cereals, legumes, fruits, vegetables, and a high consumption of fast foods were characteristics typically found in obese individuals compared to controls. A significant association between genotype I/I (SNP19 of CAPN10) and excess weight was found even with an active lifestyle. In addition, significant associations between the C/C genotype of the UCP3 gene and the G/G and T/T genotypes of the FTO gene and excess weight were found only in young sedentary individuals. Conclusions: In this population, inadequate diet and sedentary lifestyle increased the risk of excess weight. Genotype I/I of SNP19 in CAPN10 was significantly associated with excess weight. In contrast, FTO and UCP3 variants exhibited effects only in sedentary environments.RESUMEN: la obesidad resulta de la interacción entre factores de riesgo genéticos y ambientales. Objetivo: evaluar el efecto de tres variantes genéticas y factores ambientales en el exceso de peso en jóvenes de 10 a 18 años de Medellín, Colombia. Materiales y métodos: se hizo un estudio transversal en 424 jóvenes divididos en tres grupos: 100 obesos, 112 jóvenes con sobrepeso, y, pareados con ellos, 212 jóvenes con peso adecuado, que conformaron el grupo de control. Se evaluó la asociación entre tres polimorfismos genéticos (UCP3- rs1800849, FTO-rs17817449 y CAPN10-rs3842570) y el exceso de peso, así como su interacción con antecedentes familiares de enfermedad, el tiempo dedicado a ver televisión y a jugar videojuegos y el consumo de alimentos. Resultados: los antecedentes familiares de obesidad, la dedicación de más de dos horas al día a ver televisión y jugar videojuegos, la falta de lactancia materna, el bajo consumo de cereales, legumbres, frutas y verduras y el gran consumo de comidas rápidas fueron más frecuentes entre los obesos que en los controles. Se observó una asociación significativa entre el genotipo I/I (SNP19 del CAPN10) y el exceso de peso, incluso en los jóvenes que llevaban una vida activa. Además, se encontró una asociación significativa entre los genotipos C/C del UCP3 y G/G y T/T del FTO y el exceso de peso, pero solo en los jóvenes sedentarios. Conclusiones: en esta población, la alimentación inadecuada y el sedentarismo aumentaron el riesgo de exceso de peso. El genotipo I/I de SNP19 del CAPN10 se asoció significativamente con el exceso de peso. Algunas variantes del FTO y el UCP3 mostraron tener efecto solo en jóvenes sedentarios

Methionine restriction-induced metabolic changes in C57BL6J mice

Introduction: Eighty percent restriction of normal dietary methionine (MR) intake has been shown to increase energy expenditure and attenuate the rate of adiposity gain in rodents, despite a paradoxical increase in energy intake. Energy expenditure in rats was shown to increase, even though physical activity level stays the same. This observation suggests that metabolic mechanisms account for the majority of increased energy expenditure measured in methionine restricted animals. Purpose: To observe and document the onset of physiological effects brought about and to determine the mechanistic role of the skeletal muscle on MR-induced metabolic changes in the C57BL6J mouse. Methods: C57BL6J mice were fed a control (CON) or MR diet for eight weeks in which food consumption, effect on body composition, physical activity, and energy expenditure were documented. Expression of skeletal muscle genes known to change with increased fatty acid oxidation (UCP3 and CPT1b) were measured post-mortem to determine any mechanistic changes of skeletal muscle fuel utilization. Results: MR-fed C57BL6J mice gain less overall body mass than CON animals, which can be measured within the first few weeks of MR intervention. Additionally, differences in energy expenditure can be measured within the first 14 days. Despite alteration in energy expenditure, MR mice maintain similar levels of activity compared to control animals. Expression of UCP3 and CPT1b, genes associated with increased fatty acid uptake and utilization in skeletal muscle do not change, suggesting increased metabolic affects of other tissues. Conclusion: MR-fed mice exhibit a similar phenotype to that previously reported in rats on MR. Shortly after consumption of MR, C57BL6J mice exhibited an increase in energy expenditure. The increase in energy expenditure in these mice was not influenced by a change in physical activity, or genes associated with increased fatty acid utilization in the skeletal muscle tissue

Reduced Coupling of Oxidative Phosphorylation In Vivo Precedes Electron Transport Chain Defects Due to Mild Oxidative Stress in Mice

Oxidative stress and mitochondrial function are at the core of many degenerative conditions. However, the interaction between oxidative stress and in vivo mitochondrial function is unclear. We used both pharmacological (2 week paraquat (PQ) treatment of wild type mice) and transgenic (mice lacking Cu, Zn-superoxide dismutase (SOD1−/−)) models to test the effect of oxidative stress on in vivo mitochondrial function in skeletal muscle. Magnetic resonance and optical spectroscopy were used to measure mitochondrial ATP and oxygen fluxes and cell energetic state. In both models of oxidative stress, coupling of oxidative phosphorylation was significantly lower (lower P/O) at rest in vivo in skeletal muscle and was dose-dependent in the PQ model. Despite this reduction in efficiency, in vivo mitochondrial phosphorylation capacity (ATPmax) was maintained in both models, and ex vivo mitochondrial respiration in permeabilized muscle fibers was unchanged following PQ treatment. In association with the reduced P/O, PQ treatment led to a dose-dependent reduction in PCr/ATP ratio and increased phosphorylation of AMPK. These results indicate that oxidative stress uncouples oxidative phosphorylation in vivo and results in energetic stress in the absence of defects in the mitochondrial electron transport chain

Voluntary exercise in the C57B1/6J mouse: phenotypic effects of varying dietary fat levels and hippocampal gene expression differences between high-level and low-level exercisers

The drive to exercise voluntarily likely results from complex interactions between genes in many organ systems and various psychological parameters, such as motivation and the perception of fatigue. Reproducible variations in exercise intensity and duration are well established in laboratory rodents, but the genes responsible remain largely unknown. Also, to date, studies addressing the adaptive changes to exercise that might prevent dietary-induced obesity have focused primarily on energy intake and nutrient oxidation/partitioning, as opposed to genetics. We hypothesize that increased voluntary physical activity may be a normal mechanism in certain rodent strains to deter dietary-induced obesity and that in an inbred strain of mice, environmentally sensitive genes must be responsible for observed differences in individual voluntary exercise performance. To study this theory, we have designed a set of experiments that establish an animal model to address whether different gene expression profiles can be detected using microarrays and confirmed with quantitative real-time PCR (qRT-PCR) in distinct exercise phenotypes. We also used the model to address whether dietary manipulations affect voluntary exercise performance in a single strain of inbred mice susceptible to dietary-induced obesity. We determined that animals weaned onto high fat diet exercise at levels significantly higher than those weaned onto low fat diet. These animals were able to maintain body weight and decrease body fat after three weeks of exercise. We also report the results and validation of three microarray comparisons using pooled RNA from the hippocampi of exercising animals. These data suggest that several genes from the HSP 70 family, specifically several molecular chaperones localized to the endoplasmic reticulum, are differentially regulated in running versus sedentary animals at several exercise time points. We suggest that increased voluntary physical activity may be an adaptive response in male C57Bl/6J mice that prevents dietary-induced obesity on high fat diets, and we demonstrate that differential gene expression profiles related to exercise could be identified in the brain using microarrays and qRT-PCR. We conclude that genes from the molecular chaperone family, a well-described environmentally sensitive gene family, are differentially regulated in response to voluntary exercise in an inbred mouse strain