School of Public Health
Permanent URI for this communityhttp://hdl.handle.net/1903/1633
The collections in this community comprise faculty research works, as well as graduate theses and dissertations.
Note: Prior to July 1, 2007, the School of Public Health was named the College of Health & Human Performance.
Browse
10 results
Search Results
Item The effects of diet and physical activity on telomere length and telomere-related genes in mice bred for high voluntary wheel running(2010) Marshall, Mallory Rachelle; Roth, Stephen M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The purpose of this study was to determine the effects of diet and physical activity on skeletal muscle telomere length and mRNA levels of components of shelterin, a six-protein complex that protects telomeres, in mice bred over 52 generations for high wheel running activity compared to control mice. Mice were fed either a regular or high-fat diet and were provided wheel access or kept in cages without wheels for 8 weeks. Telomere length was significantly longer in mice fed a high-fat diet compared to those on a regular diet, but no other differences were observed. There were no differences in mRNA levels of the telomere-protecting shelterin components Trf1, Trf2, Pot1a, or Pot1b for diet, wheel access, or selection. High-fat diet may result in telomere dysfunction in these young mice, but we were unable to support our hypothesis that exercise would modify telomere length or shelterin mRNA levels in these mice.Item ANDROGEN RECEPTOR POLYGLUTAMINE REPEAT LENGTH AFFECTS RECEPTOR ACTIVITY AND C2C12 CELL MYOGENIC POTENTIAL(2010) Sheppard, Ryan Lance; Roth, Stephen M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Testosterone (T) has a strong anabolic effect on skeletal muscle and is believed to exert its local effects via the androgen receptor (AR). The AR harbors a polymorphic stretch of glutamine repeats demonstrated to inversely affect receptor transcriptional activity in prostate and kidney cells. However, longer AR glutamine repeat lengths are associated with greater lean body mass and higher serum T in humans. The effects of AR glutamine repeat length on skeletal muscle are unknown. Purpose:To determine the effects of AR glutamine repeat length on AR function in skeletal muscle cells. Methods:AR expression vectors carrying 14, 24, and 33 glutamine repeats, respectively, were constructed and AR transcriptional activity was determined in transfected C2C12 myoblasts using an AR sensor plasmid. Each vector was subsequently stably transfected into C2C12 cells to create 3 independent cell lines: C2C12AR14, C2C12AR24, and C2C12AR33. Cellular proliferation and creatine kinase (CK) activity were determined. Gene expression was assessed via RT-PCR. Myosin expression, myotube formation, and myonuclear fusion index were examined immunohistochemically. Results: Transcriptional activity increased with increasing repeat length (3.91±0.26 vs. 25.21±1.72 vs. 36.08±3.22 relative light units in AR14, AR24, and AR33, respectively; p<0.001), in response to T. Ligand activation ratio indicated significant ligand-independent AR transcriptional activity. Significant AR protein expression was only detected in AR14 myoblasts. In contrast, AR mRNA expression was elevated in each stable line in the myoblast stage and throughout differentiation. The proliferation of AR33 cells was significantly decreased vs. AR14 (20512.3±1024.0 vs. 27604.17±1425.3, p<0.001) after 3 days. The CK activity of AR14 cells was decreased in comparison to AR24 and AR33 cells (54.9±2.9 vs. 68.3±2.2 and 70.8±8.1 units/μg protein, respectively; p<0.05) after 5 days of differentiation. The myonuclear fusion index was lower for both AR14 (15.21±3.24%, p<0.001) and AR33 (9.97±3.14%, p<0.001) in comparison to WT C2C12 cells (35.07±5.60%). Both AR14 and AR33 cells displayed atypical myotube morphology. RT-PCR revealed differences in the expression of genes involved in differentiation, cell fusion, and cell cycle progression. Conclusion: AR polyglutamine repeat length affects receptor activity and alters the growth and development of C2C12 cells. This polymorphism may explain some of the heritability of muscle mass in humans.Item The influence of visfatin and visfatin gene polymorphisms on glucose and obesity-related variables and their responses to aerobic exercise training(2008-08-12) McKenzie, Jennifer A; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Adipokines, soluble factors produced by adipocytes, may help to connect diabetes and obesity; one such adipokine is visfatin. Previous research has linked visfatin and visfatin gene (PBEF1) polymorphisms with glucose and obesity-related conditions; however, less is known regarding visfatin's response to an aerobic exercise training intervention, and no one, to our knowledge, has examined whether polymorphic variation in the PBEF1 gene affects aerobic exercise training-induced changes in glucose and obesity-related variables. Thus, this retrospective study investigated whether 6 months of aerobic exercise training reduced plasma visfatin levels in individuals with impaired glucose tolerance (IGT) or normal glucose tolerance (NGT). In addition, we examined the influence of common PBEF1 gene polymorphisms (-4689 G>T, -1543 C>T, -1001 T>G, -948 G>T, and SER301SER) and haplotypes on glucose and obesity-related variables and their responses to aerobic exercise training. Following the completion of 6 weeks of dietary stabilization, 116 healthy, sedentary, middle-aged, Caucasian men and women underwent 6 months of aerobic exercise training. Glucose total area under the curve (AUC), insulin AUC, and insulin sensitivity were measured via oral glucose tolerance tests. Plasma visfatin was measured using an enzyme immunoassay in 67 of the participants (22 with IGT, 45 with NGT), and standard techniques were used to assess lipoprotein-lipid and body composition variables. Restriction fragment length polymorphism techniques and TaqMan assays were used to determine PBEF1 genotypes. We found that plasma visfatin levels were comparable in IGT and NGT individuals at baseline and increased similarly in both groups in response to aerobic exercise training. We also found associations at baseline between glucose and obesity-related variables and PBEF1 gene variants, with -4689, -1001, -948, and SER301SER variant allele groups and PBEF1 variant allele-containing haplotypes having higher insulin sensitivity. Last, PBEF1 genetic variation influenced the aerobic exercise training-induced change in glucose and obesity-related variables. Moreover, the -948 polymorphism, TCGTT haplotype, and TCGGT haplotype were associated with lipoprotein-lipid changes with training, and the SER301SER polymorphism influenced changes in BMI and body fat. Future studies need to address the functional significance of PBEF1 polymorphisms and haplotypes and clarify mechanisms connecting visfatin to glucose and obesity-related phenotypes.Item Influence of AT1R polymorphisms and aerobic exercise training on angiotensin II, oxidative stress and urinary nitric oxide(2007-04-26) Fenty, Nicola Melissa; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Oxidative stress is implicated in the pathogenesis of cardiovascular disease (CVD) and angiotensin II (AngII), via the type 1 receptor (AT1R), is a major factor contributing to oxidative stress. Protection against oxidative injury is provided by several antioxidants, including superoxide dismutase (SOD). Aerobic exercise training (AEX) is a non-pharmacological intervention that reduces the risk of CVD, partly through reducing levels of oxidative stress. We investigated whether the AT1R A1166C and -825 T/A polymorphisms and AEX influence oxidative stress, urinary NOx and plasma AngII. One hundred sedentary, hypertensive individuals underwent 6 months of standardized AEX. Plasma levels of AngII and SOD, and urinary excretion of NOx and 8-iso-PGF2α were measured before and after AEX. Subject characteristics and baseline values of outcome variables were similar among all genotype groups. Overall, there was a significant increase in 8-iso-PGF2α (p = 0.002) and a significant decrease in NOx excretion (p = 0.0001) however, there were no significant changes in SOD activity or AngII levels with AEX. Neither oxidative stress markers nor urinary NOx were significantly different between genotype groups with AEX. There was a significant difference in AngII levels with AEX between A1166C genotype groups (p = 0.04) resulting in a significant interactive effect of the A1166C polymorphism and AEX on the change in AngII (p < 0.05). The TT genotype group of the -825 T/A polymorphism had a significant reduction (p = 0.02) in plasma AngII, while there was no change in carriers of the A allele. Risk allele analysis revealed that there was a significant reduction in plasma AngII (p = 0.04), a significant increase in 8-iso-PGF2α (p = 0.01) and a significant decrease in urinary NOx (p = 0.0001) with AEX in individuals with 2 risk alleles. Our findings suggest that variation in the AT1R gene is associated with differential changes in plasma AngII but not with oxidative stress. Furthermore, our results may have clinical implications for the prescription of AEX in a population at risk for CVD as exercise intensities that surpass moderate intensity, may attenuate some of the beneficial effects of regular exercise by leading to increased oxidative stress.Item The Influence of Insulin-like Growth Factor Pathway Gene Polymorphisms on the Strength Training Response of Muscle Phenotypes in Older Adults(2006-11-27) Hand, Brian Dudley; Hurley, Ben; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Strength training (ST) is considered an intervention of choice for the prevention and treatment of the adverse consequences of sarcopenia. Our group previously reported that the CA dinucleotide repeat polymorphism in the promoter region of the insulin-like growth factor 1 (IGF1) gene influenced the muscle strength response to ST in Caucasians. Other studies have shown that the insulin-like growth factor binding protein-3 (IGFBP-3) is a modulator of IGF-1 in circulation and is present in skeletal muscle. The -202 polymorphism in the promoter region of the IGFBP3 gene has been shown to influence IGFBP-3 levels. In addition, there have been reports that IGF-1 and calcineurin are linked in a common pathway to induce skeletal muscle cell hypertrophy. A previous study has shown that an insertion/deletion (I/D) polymorphism in the gene encoding the regulatory subunit of calcineurin, calcineurin B, influences cardiac hypertrophy. To examine the influence of these IGF pathway gene polymorphisms on muscle mass and strength responses to ST, we studied 128 Caucasian and African American men and women before and after a 10-wk single-leg knee extension ST program. One repetition maximum strength (1 RM), muscle volume (MV), and muscle quality (MQ) were assessed at baseline and after 10 wk of ST. There was a significant combined gene effect, including both IGF1 main effect and IGF1 by calcineurin B (PPP3R1) gene by gene interaction effect, for change in strength with ST (P < 0.01). There was also a significant combined gene effect for IGF1 on change in MQ (P < 0.05). The gene by gene interaction of IGF1 and PPP3R1 by itself, approached significance for change in strength with ST (P = 0.07) and was right on the border of significance for change in MQ (P = 0.05). Moreover, PPP3R1 II homozygotes approached significance for a greater increase in MV with ST than PPP3R1 D-allele carriers (P = 0.06). There were no significant combined gene effect for PPP3R1 (i.e., PPP3R1 main effect combined with PPP3R1 by IGF1 interaction effect) for change in strength or MQ with ST. Also, there were no significant influences of the IGFBP3 polymorphism on muscle phenotypic responses to ST. These data extend our previous findings for IGF1 by indicating that IGF pathway gene polymorphisms may influence muscle phenotypic responses to ST in Caucasian and African American older men and women.Item LOX-1 genotype, dietary fat intake, and aerobic exercise training: Influence on endothelial function, oxidative stress, lipoprotein-lipids, and soluble LOX-1(2006-07-25) Ellis, Tina Janelle; Hagberg, James M.; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The lectin-like oxidized LDL receptor (LOX-1) is the major receptor for oxidized LDL (ox-LDL) in endothelial cells and plays a major role in the initiation and progression of atherosclerosis. Ox-LDL via LOX-1 causes endothelial activation and injury, induces lipid peroxidation, and alters inflammatory gene expression, and variation in the LOX-1 gene has been associated with cardiovascular disease risk. In addition, a soluble form of LOX-1 has been identified in plasma and may predict atherosclerotic disease progression. Thus, the purpose of this study was to investigate the effect of the LOX-1 3'UTR C/T and G501C polymorphisms on endothelial function, oxidative stress, plasma lipoprotein-lipids, and soluble LOX-1. The effect of these polymorphisms on the responses to dietary fat intake and aerobic exercise training was also examined. Forearm blood flow was measured using venous occlusion plethysmography at rest and during reactive hyperemia, and plasma levels of nitrates/nitrites, nitrotyrosine, ox-LDL, total antioxidant capacity, lipoprotein-lipids, and soluble LOX-1 were measured before and after six months of aerobic exercise training. The dietary ratio of polyunsaturated fat to saturated fat (P:S ratio) was determined using 7-day food records. The 3'UTR/CC and 501GC+CC groups had significantly higher baseline soluble LOX-1 levels than the CT/TT and GG groups, respectively. The G501C polymorphism was a significant predictor of baseline soluble LOX-1 levels, even after accounting for age, gender, race, BMI, and the 3'UTR polymorphism (p=0.024). There was a significant interaction between the 3'UTR polymorphism and dietary fat intake for plasma ox-LDL levels (p=0.011). At a high P:S ratio, the 3'UTR/CC group had significantly higher ox-LDL levels than the TT group (p=0.025). The opposite relationship was found at a low P:S ratio (p=0.044). The 3'UTR polymorphism also influenced changes in plasma TG levels with exercise training (p=0.036), while the G501C polymorphism influenced changes in soluble LOX-1 levels (p=0.012). In conclusion, variation in the LOX-1 gene does not appear to be associated with endothelial function, oxidative stress, or plasma lipid levels, but may influence changes in these variables in response to dietary fat intake and exercise training. Moreover, polymorphisms in LOX-1, especially the G501C polymorphism, may regulate circulating levels of soluble LOX-1.Item Myostatin Related Gene Associations with Muscle Mass and Strength in Humans.(2006-07-14) Walsh, Sean; Roth, Stephen M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)INTRODUCTION: The gradual decline in muscle mass with age is known as sarcopenia, and has been associated with an increased risk of falls, hip fractures, and functional decline. However, there is large inter-individual variability in this decline, even among people of a similar age and sex. Heritability studies have shown that genetic factors can account for up to 90% of this variation in muscle mass and ~65% in muscle strength. Myostatin is a negative regulator of skeletal muscle and plays a key role in muscle development and the maintenance of muscle mass. However, DNA sequence variation within this gene has not been consistently associated with skeletal muscle mass nor muscle strength in humans. PURPOSE: The purpose of this dissertation was to examine genetic variation in follistatin and Activin RIIB (ACVR2B), two myostatin related genes, to explore associations with skeletal muscle related phenotypes. METHODS: Three hundred fifteen Caucasian males and 278 Caucasian females aged 19-90 years from the Baltimore Longitudinal Study of Aging were genotyped to determine respective haplotype groupings. Whole-body soft tissue composition was measured by dual-energy X-ray absorptiometry. Peak torque (strength) was measured using an isokinetic dynamometer. RESULTS: Women heterozygous for ACVR2B haplotype groups 1 and 2 exhibited significantly less concentric quadriceps muscle strength than women homozygous for haplotype group 2 (108.7 ± 2.2 vs 118.6 ± 4.1 Nm, .52rad/sec, respectively, p <0.05). No significant association was observed in men. However, men homozygous for follistatin haplotype group 1 exhibited significantly greater total leg FFM than men heterozygous for follistatin haplotype groups 1 and 3 (17.8 ± 0.2 vs 16.7 ± 0.4 kg, respectively, p <0.05) and significantly greater total leg FFM than non-carriers of follistatin haplotype group 1 (17.8 ± 0.2 vs 16.5 ± 0.5 kg, respectively, p <0.05). Moreover, male carriers of follistatin haplotype group 3 exhibited significantly less total leg FFM than non-carriers (16.6 ± 0.3 vs 17.5 ± 0.2 kg, respectively, p <0.05). No significant associations between these groups were observed in women. CONCLUSIONS: The data indicate that the ACVR2B and follistatin loci may contribute to the inter-individual variation in skeletal muscle mass and strength.Item EXERCISE BEHAVIOR AND MAINTENANCE OF CEREBRAL CORTICAL ACTIVITY DURING COGNITIVE CHALLENGE IN MIDDLE-AGED MEN AND WOMEN GENETICALLY AT RISK FOR DEMENTIA: A MEGNETOENCEPHALOGRAPHIC STUDY(2005-04-20) Deeny, Sean Patrick; Hatfield, Brad D; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Exercise is known to protect and enhance cognitive function in normal aging through increased blood flow and upregulation of neurotrophic factors in the brain. One recent study suggests that carriers of a known genetic risk factor for Alzheimer's disease (AD), the apolipoprotein E (APOE) E4 allele, may exhibit a more profound benefit of exercise on neurocognitive function relative to non-E4 carriers. Brain imaging studies in cognitively normal, middle-aged E4 carriers have revealed deficits in temporal and parietal cortical function even in the absence of clinical symptoms of dementia. As exercise has been shown to protect these regions in normal aging, and even enhance cortical functioning, the current study employs magnetoencephalographic (MEG) measures of cortical activation during the Ericksen flanker task and the Sternberg working memory task to examine whether highly physically active 50-70 year old E4 carriers and non-carriers, who are free from dementia, exhibit greater cortical activation in task-related regions relative to their low-active counterparts. The results revealed that high-active participants, regardless of genotype, exhibited greater activation on the Ericksen flanker task in the right frontal and right temporal regions relative to low-active participants, while performing similarly on accuracy and reaction time (RT). On the Sternberg working memory task high-active E4 carriers exhibited greater activation than low-active E4 carriers in the right temporal region, while being undifferentiated from both the high-active and low-active non-E4 carriers. This effect was most pronounced in the 150-200 ms post-stimulus time window. All groups performed similarly on accuracy and RT. The results suggest that high-resolution brain imaging methods are sensitive to differences in brain function in populations at different genetic risk for dementia prior to any signs of clinical impairment. Furthermore, the relationships between physical activity and brain function are measurable and distinguishable between groups of different genetic susceptibility on tasks and brain regions specific to AD-related neurocognitive decline. The findings support the notion that populations genetically at risk for dementia who remain sedentary may be at greater risk for decline in brain function relative to those who are physically active.Item DNA SEQUENCE VARIATION IN THE PROMOTER REGION OF THE VEGF GENE: IMPACTS ON VEGF GENE EXPRESSION AND MAXIMAL OXYGEN CONSUMPTION(2005-07-29) Prior, Steven John; Roth, Stephen M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Maximal oxygen consumption (Vo2max) is inversely associated with cardiovascular and all-cause mortality and is responsive to aerobic exercise training. A portion of the increase in Vo2max with aerobic exercise training can be attributed to an increase in skeletal muscle capillarity (i.e., angiogenesis), which contributes to increased blood flow and oxygen extraction in working skeletal muscle. One contributing factor to exercise-induced angiogenesis is vascular endothelial growth factor (VEGF), as it is an endothelial cell proliferation and migration factor that is upregulated by acute aerobic exercise. Significant variability has been observed in VEGF protein levels, VEGF gene expression, skeletal muscle capillarity, and Vo2max before and after aerobic exercise training. Additionally, variability is found in the DNA sequence of the gene encoding VEGF. Variation in the VEGF gene has the ability to impact VEGF gene expression and VEGF protein level and because of the relationship between VEGF, angiogenesis, and Vo2max, we hypothesized that variation in the VEGF gene is related to VEGF gene expression in human myoblasts, plasma VEGF level, and Vo2max before and after aerobic exercise training. The present report shows that VEGF promoter region haplotype impacts VEGF gene expression in human myoblasts in vitro. It was also found that VEGF promoter region haplotype was associated with Vo2max in older men and women before and after exercise training in a manner that is consistent with the results of the VEGF gene expression experiments. Additionally, we found that plasma VEGF level was not associated with VEGF promoter region haplotype, nor did plasma VEGF level correlate with baseline Vo2max or the change in Vo2max with aerobic exercise training. To date, we are the first to report that VEGF promoter region haplotype impacts VEGF gene expression in human myoblasts and is associated with Vo2max. These results have potential implications for aerobic exercise training and may also contribute to the understanding of the function of the VEGF promoter region in different cell types. Furthermore, these results may prove relevant in the study of pathological conditions which can be affected by angiogenesis, namely obesity, cancer, coronary artery disease, and peripheral artery disease.Item Influence of Vitamin D Receptor Gene Polymorphisms on Changes in Insulin Sensitivity with Aerobic Exercise Training(2005-01-24) Harne, Amanda Janel; Hagberg, James M; Kinesiology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The purpose of the study was to examine the influence of the FokI and BsmI polymorphisms of the vitamin D receptor gene on changes in insulin sensitivity with aerobic exercise training in men and women at increased risk for type 2 diabetes mellitus (T2DM). Subjects were genotyped and underwent oral glucose tolerance tests before and after six months of training. Due to mis-genotyping of the BsmI polymorphism, results for that variant were not reported. There were no significant differences between FokI genotype groups in insulin sensitivity before or after training. However, among subjects who completed training, FF homozygotes had significantly higher baseline fasting glucose and insulin levels than f allele carriers. While the FokI polymorphism does not appear to mediate training-induced changes in indices of glucose and insulin metabolism, it may influence fasting glucose and insulin levels and the development of insulin resistance in individuals at increased risk for T2DM.