Receptor Gamma Coactivator 1-alpha Gene Research Articles

THE RELATIONSHIP BETWEEN POLYMORPHISM 1357 G → A OF THE CNTF GENE AND GLY482SER OF THE PPARGC1A GENE WITH MUSCLE STRENGTH

Muscle strength is the process of energy synthesis during certain tasks in muscle fibers. In modern sports and sports medicine, exploring methods to enhance muscle strength through targeted exercises and training programs is a key area of focus. While many athletes can achieve the physical conditioning necessary for competitive performance, the role of genetics in sports has gained attention as it offers insights for optimizing training strategies and enhancing performance based on individual genetic profiles. Among the well-researched genes in muscle strength studies are the ciliary neurotrophic factor gene (CNTF) and the peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene (PPARGC1A). This study investigates the relationship between polymorphisms in these genes and the function of motor units in muscle fibers. The aim of the study is to analyze and explain the mechanisms by which polymorphisms in the CNTF and PPARGC1A genes influence muscle strength. Materials and Methods. Following PRISMA guidelines, a comprehensive literature review was conducted using relevant keywords across leading scientometric databases. Results and Discussion. This article explores the relationship between genetic variants of the CNTF and PPARGC1A genes and muscle strength in adults. Specifically, it examines the impact of the CNTF 1357 G→A and PPARGC1A Gly482Ser polymorphisms on muscle strength gains in response to strength training. The study results indicate that these genetic variations significantly affect individual differences in response to exercise. Notable fluctuations in strength gains and changes in maximal voluntary contraction were observed. The data underscore the need for further research to deepen our understanding of how the CNTF and PPARGC1A genes influence muscle adaptation to training, as well as to assess their roles across different populations and training conditions. It has been found out that the AA genotype of the 1357 G→A variation leads to a functionally inactive neurotrophic factor protein, thereby significantly diminishing its myotrophic effect on skeletal muscles. Regarding the Gly482Ser polymorphism, homozygosity for the T allele is associated with reduced skeletal muscle metabolism and decreased oxidative activity. Conclusions. The results obtained can be applied for developing personalized training programs and improving practice of sports medicine and rehabilitation, thus facilitating the more effective achievement of individual fitness and health goals.

A randomized, placebo-controlled first-in-human study of oral TQS-168 in healthy volunteers: Assessment of safety, tolerability, pharmacokinetics, pharmacodynamics, and food effect.

TQS-168, a first-in-class small-molecule inducer of peroxisome proliferator-activated receptor gamma coactivator 1-alpha gene expression, is in development for the treatment of amyotrophic lateral sclerosis. A single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study of TQS-168 was carried out in healthy male subjects to investigate safety, tolerability, pharmacokinetics (PK), food effect, and preliminary pharmacodynamic effects (PD). Since solubility enhancement could be beneficial, assessment of three formulations was incorporated into the study using an integrated rapid manufacturing and clinical testing approach. Dosing in the SAD part was initiated with a crystalline methylcellulose (MC) suspension, and then spray-dried dispersion (SDD) and hot-melt extrusion (HME) suspensions were evaluated. The HME and SDD formulations showed two and fourfold higher exposure than the MC suspension, respectively, and the SDD formulation was selected for progression to subsequent SAD and MAD cohorts, in which there was further investigation of the food effect on exposure in addition to assessments of safety, tolerability, PK, and PD. Cmax and AUC plasma exposures of TQS-168 were supra-proportional at higher doses, irrespective of formulation. Median Tmax for TQS-168 occurred between 0.5 and 4.0 h post-dose and occurred later with higher doses. Geometric mean half-lives (T1/2) for TQS-168 were independent of formulation and food, ranging from 3.2 to 10.5 h following single doses and 4.1 to 7.3 h following multiple doses. Food blunted TQS-168 Cmax but had minimal impact on AUC. TQS-168 was considered to be safe and generally well tolerated following single and multiple oral doses. The SDD formulation was selected for future patient studies.

Vitamin D Status and Resting Metabolic Rate May Modify through Expression of Vitamin D Receptor and Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Gene in Overweight and Obese Adults

Background: Resting metabolic rate (RMR) used to prognosticate and measure the amount of energy required. Vitamin D is known as a new predictor of RMR. The aim of this study is to investigate the relationship between vitamin D effects on RMR in connection with the vitamin D receptor (VDR) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) gene expression. Methods: We enrolled 298 overweight and obese adults in this cross-sectional study. Body mass index (BMI), fat mass, fat-free mass, insulin level, visceral fat, and vitamin D status were assessed. RMR was measured by means of indirect calorimetry. The real-time polymerase chain reaction using specific primer pairs for VDR and PGC-1α was performed. Results: There were significant differences in terms of fat free mass, fat percentage, insulin levels, RMR/kg body weight, and RMR/BMI, VDR, and PGC-1α among participants were categorized based on the vitamin D status. But after using general linear model for adjusting, all significant results missed their effectiveness except RMR/kg body weight and VDR. Linear regression analysis used to show the mediatory role of VDR and PGC-1α on the RMR/kg body weight and vitamin D status relationship. Our results showed that VDR had a mediatory effect on the relationship between RMR/kg body weight and vitamin D status (β = 0.38, 95% CI –0.48 to 1.60; β = –1.24, 95% CI –5.36 to 1.70). However, PGC-1α did not affect the relationship between RMR/kg body weight and vitamin D status (β = 0.50, 95% CI = –0.02 to 3.42; β = 0.59, 95% CI 0.14–3.90). Conclusion: Our study showed the mediatory effect of VDR gene expression in the association of 25(OH)₂D plasma levels and resting metabolic rate among obese individuals.

Transcriptional Control of the Pgc-1α Gene in Skeletal Muscle In Vivo

Endurance exercise promotes mitochondrial biogenesis in skeletal muscle possibly by inducing peroxisome proliferator-activated receptor gamma coactivator 1alpha gene transcription through activation of the p38 mitogen-activated protein kinase pathway. A novel imaging analysis revealed the importance of activating transcription factor 2 and histone deacetylase 5/myocyte enhancer factor 2 in the regulation of the Pgc-1alpha gene in skeletal muscle in vivo.

The Peroxisome Proliferator-activated Receptor Gamma Coactivator-1 Alpha Gene (PGC-1α) is Not Associated with Type 2 Diabetes Mellitus or Body Mass Index Among Hispanic and Non Hispanic Whites from Colorado

The objective of the study was to test for an association between type 2 diabetes mellitus (T2DM) and body mass index (BMI) and three single nucleotide polymorphisms (SNP)s in the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) gene. We were also interested in whether these associations differed by tertiles of diet, physical activity or presence of polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene among Hispanics and Non-Hispanic Whites (NHW) from Colorado. We studied 216 Hispanic pedigrees (1850 nuclear families) and 236 NHW pedigrees (1240 families) from the San Luis Valley and Denver. We genotyped the Gly482Ser, Thr528Thr and Thr612Met polymorphisms in the PGC-1alpha gene and the Pro12Ala polymorphism of the PPAR-gamma gene. Historical physical activity (average METS/week) as well as average dietary intake over the past year was assessed by self-report. Data were analyzed using the Family Based Association Test (FBAT) as well as generalized estimating equations (GEE). We did not find any significant association between three SNPs in the PGC-1alpha gene and T2DM in Hispanics or NHW; however, using FBAT, we found the common Thr612Thr allele of the PGC-1alpha gene to be associated with T2DM among Hispanic subjects carrying the rare Pro12Ala allele of the PPAR-gamma gene (p=.003). We found similar associations when we considered a haplotype containing that allele (p=.002). However, the results of the GEE analysis did not confirm these findings: odds ratio (OR)=1.68, 95% CI (0.5, 5.2) suggesting these results may due to chance. BMI also did not show any consistent associations with the PGC-1alpha gene. In conclusion, we did not find an association between the PGC-1alpha gene and T2DM or BMI and there were no consistent interactions with diet, physical activity or the Pro12Ala polymorphism of the PPAR-gamma gene.