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Nathan Goodyear

Estrogenic regulation of skeletal muscle proteome: a study of premenopausal women and p... - 0 views

  • Female aging is characterized by menopausal change in sex steroid hormones concomitant to increase in aging-related decrements in skeletal muscle performance that can be attenuated by HRT use
  • The major canonical pathways found to be differentially regulated included mitochondrial dysfunction, oxidative phosphorylation, glycolysis, and TCA-cycle, strong indicators for affected energy metabolism
  • E2 to exert anti-apoptotic effects in muscle progenitor cells by improving mitochondrial function
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  • E2 is a major regulator of human skeletal muscle signaling in women
  • After menopause, when ovarian E2 production is ceased, the prevalence of cardio-metabolic diseases increases. Our result that different trajectories of the energy pathways in the skeletal muscle may be regulated by E2 provides candidate molecules as key targets for future interventions to prevent or treat postmenopausal metabolic dysregulation
    Study finds Estradiol regulates human skeletal muscle cell signaling (mitochondrial function, oxidative phosphorylation, glycolysis, and TCA cycle) in study of pre/post menopause women through proteome analysis. This study would have been complete if they had carried to search beyond that of protein to epigenetics.
Nathan Goodyear

Impact of an Exercise Intervention on DNA Methylation in Skeletal Muscle From First-Deg... - 0 views

  • epigenetic modifications of single genes have been shown to affect the pathogenesis of T2D
  • An FH of T2D is an independent predictor of future risk for the disease
  • exercise for 6 months is associated with epigenetic changes, e.g., decreased DNA methylation of RUNX1 and MEF2A, two key transcription factors involved in exercise training (), of THADA, previously associated with T2D (), and of NDUFC2, which is part of the respiratory chain () was observed after exercise
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  • exercise changed both DNA methylation and expression of a number of genes, including ADIPOR1, ADIPOR2, and BDKRB2, encoding receptors for adiponectin and bradykinin, respectively, which both regulate metabolism in muscle
  • we cannot draw a conclusion as to whether differential expression is a consequence rather than a cause of changes in methylation
  • ageing is associated with increased DNA methylation and decreased expression of genes involved in oxidative phosphorylation in human muscle
  • exercise can induce genome-wide epigenetic changes in human muscle and that the response may differ in people with different genetic predispositions to metabolic disease
    Six months of exercise induce epigenetic changes through decrease in methylation.  This study was designed to look at those with a family risk of DM.  They found a difference in the methylation status of muscle between those with a family h/o diabetes and those without.  This would have implications in therapeutic difference prior to diagnosis.  Even a increased VO2max and skeletal muscle mitochondrial density was found to be the result of decreased methylation of the NDUFC2 gene after exercise.
Nathan Goodyear

Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle: Cell Metabolism - 0 views

  • our results provide evidence to suggest that acute exercise induces gene-specific DNA hypomethylation in human skeletal muscle
  • Our results suggest that DNA methylation is a component of the exercise-induced effect on expression of these genes.
  • Caffeine exposure decreased promoter methylation of Pgc-1α, Tfam, Mef2a, Cs, and Pdk4
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  • the effect of exercise on DNA methylation in human skeletal muscle and provide evidence that acute exercise alters promoter methylation of exercise-responsive genes in a dose-dependent manner
  • DNA methylation was unaltered 48 hr after a 3-week exercise training program, whereas RNA expression of PGC-1α and TFAM promoters was elevated (data not shown), further suggesting that DNA hypomethylation is a transient mechanism involved in mRNA synthesis
  • Our findings that ionomycin, AICAR, or ROS production increased mRNA expression without altering promoter methylation may support the notion that DNA methylation does not exclusively control exercise-induced gene expression
  • acute exercise leads to transient changes in DNA methylation in adult skeletal muscle
    Small study finds acute exercise is associated with epigenetic alteration of muscle through methylation.  This study found a hypomethylation of the genes PGC-1alpha, PDK4, and PPAR-delta with a respondent increase in expression.  The methylation activity was in the promoter region of these genes.
Nathan Goodyear

An integrative analysis reveals coordinated reprogramming of the epigenome and the tran... - 0 views

  • contribution to the training response of the epigenome as a mediator between genes and environment
  • Differential DNA methylation was predominantly observed in enhancers, gene bodies and intergenic regions and less in CpG islands or promoters
  • highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus
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  • The health benefits following exercise training are elicited by gene expression changes in skeletal muscle, which are fundamental to the remodeling process
  • there is increasing evidence that more short-term environmental factors can influence DNA methylation
  • dietary factors have the potency to alter the degree of DNA methylation in different tissues, 9,10 including skeletal muscle
  • In one study, a single bout of endurance-type exercise was shown to affect methylation at a few promoter CpG sites
  • In the context of diabetes, exercise training has been shown to affect genome-wide methylation pattern in skeletal muscle,13 as well as in adipose tissue.
  • physiological stressors can indeed affect DNA methylation
  • training intervention reshapes the epigenome and induces significant changes in DNA methylation
  • the findings from this tightly controlled human study strongly suggest that the regulation and maintenance of exercise training adaptation is to a large degree associated to epigenetic changes, especially in regulatory enhancer regions
  • Endurance training [after training (T2) vs. before training (T1)] induced significant (false discovery rate, FDR< 0.05) methylation changes at 4919 sites across the genome in the trained leg
  • identified 4076 differentially expressed genes
  • a complementary approach revealed that over 600 CpG sites correlated to the increase in citrate synthase activity, an objective measure of training response (Figure S4 and Dataset S14). This might imply that some of these sites could influence the degree of training response.
  • As expected by a physiological environmental trigger on adult tissue, the observed effect size on DNA methylation was small in comparison to disease states such as cancer
  • a preferential localization outside of CpG Islands/Shelves/Shores
  • endurance training especially influences enhancers
  • negative correlation was more prominent for probes in promoter/5′UTR/1st exon regions, while gene bodies had a stronger peak of positive correlation
  • The significant changes in DNA methylation, that primarily occurred in enhancer regions, were to a large extent associated with relevant changes in gene expression
  • The main findings of this study were that 3 months of endurance training in healthy human volunteers induced significant methylation changes at almost 5000 sites across the genome and significant differential expression of approximately 4000 genes
  • DMPs that increased in methylation were mainly associated to structural remodeling of the muscle and glucose metabolism, while the DMPs with decreased methylation were associated to inflammatory/immunological processes and transcriptional regulation
  • This suggests that the changes in methylation seen with training were not a random effect across the genome but rather a controlled process that likely contributes to skeletal muscle adaptation to endurance training
  • Correlation of the changes in DNA methylation to the changes in gene expression showed that the majority of significant methylation/expression pairs were found in the groups representing either increases in expression with a concomitant decrease in methylation or vice versa
  • The fraction of genes showing both significant decrease in methylation and upregulation was 7.5% of the DEGs or 2.3% of all genes detected in muscle tissue with at least one measured DNA methylation position. Correspondingly, 7.0% of the DEGs or 2.1% of all genes showed both significant increase in methylation and downregulation
  • we show that DNA methylation changes are associated to gene expression changes in roughly 20% of unique genes that significantly changed with training
  • Examples of structural genes include COL4A1, COL4A2 and LAMA4. These genes have also been identified as important for differences in responsiveness to endurance training
  • methylation status could be part of the mechanism behind variable training response
  • Among the metabolic genes, MDH1 catalyzes the reversible oxidation of malate to oxaloacetate, utilizing the NAD/NADH cofactor system in the citric acid cycle and NDUFA8 plays an important role in transferring electrons from NADH to the respiratory chain
  • PPP1R12A,
  • In the present study, methylation predominantly changed in enhancer regions with enrichment for binding motifs for different transcription factors suggesting that enhancer methylation may be highly relevant also in exercise biology
  • Of special interest in the biology of endurance training may be that MRFs, through binding to the PGC-1α core promoter, can regulate this well-studied co-factor for mitochondrial biogenesis
  • That endurance training led to an increased methylation in enhancer regions containing motifs for the MRFs and MEFs is somewhat counterintuitive since it should lead to the repression of the action of the above discussed transcription factors
  • decrease with training in this study, including CDCH15, MYH3, TNNT2, RYR1 and SH3GLB1
  • expression of MEF2A itself decreased with training
  • this study demonstrates that the transcriptional alterations in skeletal muscle in response to a long-term endurance exercise intervention are coupled to DNA methylation changes
  • We suggest that the training-induced coordinated epigenetic reprogramming mainly targets enhancer regions, thus contributing to differences in individual response to lifestyle interventions
  • a physiological health-enhancing stimulus can induce highly consistent modifications in DNA methylation that are associated to gene expression changes concordant with observed phenotypic adaptations
    Exercise alters gene expression via methylation--the power of epigenetics.  Interestingly, the majority of the methylation was outside the CPG island regions.  This 3 month study found methylation of 5,000 sites across the genome resulting in altered expression of apps 4,000 genes.  The altered muscle changes of the endurance training was linked to DNA methylation changes.
Nathan Goodyear

Frontiers | Branched-Chain Amino Acid Ingestion Stimulates Muscle Myofibrillar Protein ... - 1 views

  • BCAAs exhibit the capacity to stimulate myofibrillar-MPS, however a full complement of EAA could be necessary to stimulate a maximal response of myofibrillar-MPS following resistance exercise
  • This information potentially has important nutritional implications for selecting amino acid supplements to facilitate skeletal muscle hypertrophy in response to resistance exercise training and the maintenance of muscle mass during aging, unloading, or disease
  • results from the present study suggest that ingesting BCAAs alone, without the other EAA, provides limited substrate for protein synthesis in exercised muscles
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  • the overall response of MPS is not maximized. Instead, the limited availability of EAA likely explains the qualitative difference in magnitude of the MPS response to ingestion of BCAAs alone and ingestion of similar amounts of BCAAs as part of intact whey protein
  • decreased EAA concentrations following leucine ingestion
  • these data support the notion that EAA availability is the rate-limiting factor for stimulating a maximal MPS response to resistance exercise with BCAA ingestion
    Complete amino acid supplementation exceeds muscle building capacity (myofibrillar-MPS) over BCAA alone.
Nathan Goodyear

Resistance Training for Glycemic Control, Muscular Strength, and Lean Body Mass in Old ... - 0 views

    8 weeks of resistance training in patients with sarcopenia and diabetes found to improve glycemic control
Nathan Goodyear

Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high-intensity ex... - 0 views

    The early post menopause phase is critical for women. This is the phase that requires intensify strategy for exercise. The ER alpha signaling is actually increased and the ability to build muscle is intensified if exercise, particularly resistance training, is employed.
Nathan Goodyear

Diabetes - 0 views

    exercise increases AMPK to improve insulin sensitivity and glucose uptake in new animal study.
Nathan Goodyear

Effects of testosterone on body composition, bone metabolism and serum lipid profile in... - 0 views

    Meta-analysis finds that Testosterone therapy in men 40+ reduced total body fat with an increase in fat free mass. 
Nathan Goodyear

Plasticity in mitochondrial cristae density allows metabolic capacity modulation in hum... - 0 views

    New study suggests endurance training can change mitochondria to improve energy production efficiency.
Nathan Goodyear

Frontiers | Nitrate Intake Promotes Shift in Muscle Fiber Type Composition during Sprin... - 0 views

    Nitrates from greens aid in athletic training.
Nathan Goodyear

Healthcare | Free Full-Text | Association of Mid-Life Changes in Body Size, Body Compos... - 0 views

    great review of the menopause transition and the effect of weight and hormones.  For example, muscle loss is found in menopause vs perimenopause.  Increased estrogen production occurs from non-ovary sites i.e. visceral and SQ fat.
Nathan Goodyear

Association between muscular strength and mortality in men: prospective cohort study | ... - 0 views

    muscle strength found to be inversely associated with mortality and cancer.
Nathan Goodyear

Association of handgrip strength to cardiovascular mortality in pre-diabetic and diabet... - 0 views

    Handgrip strength test is found to be associated inversely with mortality and cardiovascular events in men and women with diabetes and glucose dysregulation.  Strength is more predictive of morality in men versus women, but this study finds predictive value for both.
Nathan Goodyear

Muscle Strength and Body Mass Index as Long-Term Predictors of Mortality in Initially H... - 0 views

    low strength via hand-grip strength test found to be associated with increased mortality risk.
Nathan Goodyear

Muscular strength in male adolescents and premature death: cohort study of one million ... - 0 views

    low muscle strength associated with increased risk of early mortality and CVD in men.
Nathan Goodyear

The Role of Post-Exercise Nutrient Administration on Muscle Protein Synthesis and Glyco... - 0 views

  • Whey protein was superior to that of casein in upregulating protein synthesis
  • ability to digest more rapidly than casein protein
  • Free form amino acid ingestion acts similarly to whey by displaying a rapid and strong increase in aminoacidemia
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  • it appears that protein synthesis rapidly increases for up to two hours after amino acid administration
  • The intervention of dietary protein or amino acid supplementation in conjunction with resistance training has proven to effectively increase protein synthesis rates
  • 291% increase in protein synthesis following the exercise bout, while protein degradation remained unchanged from baseline quantities
  • it has been established that post-exercise EAA supplementation stimulates protein synthesis, in conjunction with a positive protein balance, comparable to that of intravenous infusion of amino acids
  • Casein and whey protein ingestion yielded similar values of net positive protein balance, and thus an overall increase in protein synthesis
  • A later analysis revealed that soy protein increased protein synthesis in rats similar to that of whey after a treadmill exercise protocol
  • A human trial, however, concluded that milk proteins (caseins and whey) in comparison to soy promoted greater muscle protein accretion when they were ingested after regular resistance training
  • Whey hydrolysate ingested after a resistance exercise bout acutely stimulated mixed muscle protein synthesis 31% greater than soy
  • adequate amount of protein (20 g) is ingested (Tipton et al., ) immediately before or after a resistance exercise bout
  • The rapid phase lasts approximately 30-60 minutes and does not require the presence of insulin
  • slow phase, which can last up to several hours if carbohydrate availability is high and insulin levels remain elevated
    Good review of recovery supplement strategy.
Nathan Goodyear

Effects of aromatase inhibition vs. testosterone in older men with low testosterone: ra... - 0 views

    No surprise that Testosterone therapy improves Testosterone levels in men with low T, but aromatase inhibition (AI) did as well.  In this study, only lean mass increased compared to Testosterone therapy and placebo.  Strength increased in both Testosterone and AI.
Nathan Goodyear

International Journal of Obesity - Identification of skeletal muscle mass depletion acr... - 0 views

    good article to review the components of body composition.
Nathan Goodyear

Interorgan ammonia trafficking in liver disease. - PubMed - NCBI - 0 views

    The primary metabolizer of ammonia is the liver; however, in liver failure, muscle mass becomes a second means to metabolize excessive ammonia.
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