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Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D.

Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Purpose: The purpose of this study was to examine the acute effects of two novel intermittent exercise prescriptions on glucose regulation and ambulatory blood pressure. Methods: Ten subjects (5 men and 5 women, ages 31.5 ± 5.42 yr, height 170.38 ± 9.69 cm and weight 88.59 ± 18.91 kg) participated

Purpose: The purpose of this study was to examine the acute effects of two novel intermittent exercise prescriptions on glucose regulation and ambulatory blood pressure. Methods: Ten subjects (5 men and 5 women, ages 31.5 ± 5.42 yr, height 170.38 ± 9.69 cm and weight 88.59 ± 18.91 kg) participated in this four-treatment crossover trial. All subjects participated in four trials, each taking place over three days. On the evening of the first day, subjects were fitted with a continuous glucose monitor (CGM). On the second day, subjects were fitted with an ambulatory blood pressure monitor (ABP) and underwent one of the following four conditions in a randomized order: 1) 30-min: 30 minutes of continuous exercise at 60 - 70% VO2peak; 2) Mod 2-min: twenty-one 2-min bouts of walking at 3 mph performed once every 20 minutes; 3) HI 2-min: eight 2-min bouts of walking at maximal incline performed once every hour; 4) Control: a no exercise control condition. On the morning of the third day, the CGM and ABP devices were removed. All meals were standardized during the study visits. Linear mixed models were used to compare mean differences in glucose and blood pressure regulation between the four trials. Results: Glucose concentrations were significantly lower following the 30-min (91.1 ± 14.9 mg/dl), Mod 2-min (93.7 ± 19.8 mg/dl) and HI 2-min (96.1 ± 16.4 mg/dl) trials as compared to the Control (101.1 ± 20 mg/dl) (P < 0.001 for all three comparisons). The 30-min trial was superior to the Mod 2-min, which was superior to the HI 2-min trial in lowering blood glucose levels (P < 0.001 and P = 0.003 respectively). Only the 30-min trial was effective in lowering systolic ABP (124 ± 12 mmHg) as compared to the Control trial (127 ± 14 mmHg; P < 0.001) for up to 11 hours post exercise. Conclusion: Performing frequent short (i.e., 2 minutes) bouts of moderate or high intensity exercise may be a viable alternative to traditional continuous exercise in improving glucose regulation. However, 2-min bouts of exercise are not effective in reducing ambulatory blood pressure in healthy adults.
ContributorsBhammar, Dharini Mukeshkumar (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Buman, Matthew (Committee member) / Swan, Pamela (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Nut consumption, specifically almonds, have been shown to help maintain weight and influence disease risk factors in adult populations. Limited studies have been conducted examining the effect of a small dose of almonds on energy intake and body weight. The objective of this study was to determine the influence of

Nut consumption, specifically almonds, have been shown to help maintain weight and influence disease risk factors in adult populations. Limited studies have been conducted examining the effect of a small dose of almonds on energy intake and body weight. The objective of this study was to determine the influence of pre-meal almond consumption on energy intake and weight in overweight and obese adults. In this study included 21, overweight or obese, participants who were considered healthy or had a controlled disease state. This 8-week parallel arm study, participants were randomized to consume an isocaloric amount of almonds, (1 oz) serving, or two (2 oz) cheese stick serving, 30 minutes before the dinner meal, 5 times per week. Anthropometric measurements including weight, waist circumference, and body fat percentage were recorded at baseline, week 1, 4, and 8. Measurement of energy intake was self-reported for two consecutive days at week 1, 4 and 8 using the ASA24 automated dietary program. The energy intake after 8 weeks of almond consumption was not significantly different when compared to the control group (p=0.965). In addition, body weight was not significantly reduced after 8 weeks of the almond intervention (p=0.562). Other parameters measured in this 8-week trial did not differ between the intervention and the control group. These data presented are underpowered and therefore inconclusive on the effects that 1 oz of almonds, in the diet, 5 per week has on energy intake and bodyweight.
ContributorsMcBride, Lindsey (Author) / Johnston, Carol (Thesis advisor) / Swan, Pamela (Committee member) / Mayol-Kreiser, Sandra (Committee member) / Arizona State University (Publisher)
Created2011
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The effects of a long-term combat deployment on a soldier's physical fitness are not well understood. In active duty soldiers, combat deployment reduced physical fitness compared to pre-deployment status, but no similar research has been performed on Army National Guard soldiers. This study is the first to identify physical fitness

The effects of a long-term combat deployment on a soldier's physical fitness are not well understood. In active duty soldiers, combat deployment reduced physical fitness compared to pre-deployment status, but no similar research has been performed on Army National Guard soldiers. This study is the first to identify physical fitness changes in Arizona National Guard (AZNG) soldiers following deployment to a combat zone and to assess the relationships between physical fitness and non-combat injuries and illness (NCII). Sixty soldiers from the Arizona National Guard (AZNG) completed a battery of physical fitness tests prior to deployment and within 1-7 days of returning from a 12-month deployment to Iraq. Pre and post-deployment measures assessed body composition (Bod Pod), muscular strength (1RM bench press, back-squat), muscular endurance (push-up, sit-up), power (Wingate cycle test), cardiorespiratory fitness (treadmill run to VO2 peak), and flexibility (sit-and-reach, trunk extension, shoulder elevation). Post deployment, medical records were reviewed by a blinded researcher and inventoried for NCII that occurred during deployment. Data were analyzed for changes between pre and post-deployment physical fitness. Relationships between fitness and utilization of medical resources for NCII were then determined. Significant declines were noted in mean cardiorespiratory fitness (-10.8%) and trunk flexibility (-6.7%). Significant improvements were seen in mean level of fat mass (-11.1%), relative strength (bench press, 10.2%, back-squat 14.2%) and muscular endurance (push-up 16.4%, sit-up 11.0%). Significant (p < 0.05) negative correlations were detected between percentage change in fat mass and gastrointestinal visits (r = -0.37); sit-and-reach and lower extremity visits (r= -0.33); shoulder elevation and upper extremity visits (r= -0.36); and cardiorespiratory fitness and back visits (r= -0.31); as well as behavioral health visits (r= -0.28). Cardiorespiratory fitness changes were grouped into tertiles. Those who lost the greatest fitness had significantly greater number of NCII visits (8.0 v 3.1 v 2.6, p = .03). These data indicate a relationship between the decline in cardiorespiratory fitness and an overall increase in utilization of medical resources. The results may provide incentive to military leaders to ensure that soldiers maintain their cardiorespiratory fitness throughout the extent of their deployment.
ContributorsWarr, Bradley (Author) / Swan, Pamela (Thesis advisor) / Lee, Chong (Committee member) / Campbell, Kathryn (Committee member) / Erickson, Steven (Committee member) / Alvar, Brent (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Heart failure is a major worldwide health concern and is the leading cause of hospitalization among elderly Americans. Approximately 50% of those diagnosed with heart failure have heart failure with preserved ejection fraction (HFPEF). HFPEF presents a therapeutic dilemma because pharmacological strategies that are effective for the treatment of heart

Heart failure is a major worldwide health concern and is the leading cause of hospitalization among elderly Americans. Approximately 50% of those diagnosed with heart failure have heart failure with preserved ejection fraction (HFPEF). HFPEF presents a therapeutic dilemma because pharmacological strategies that are effective for the treatment of heart failure and reduced ejection fraction have failed to show benefit in HFPEF. Long term moderate intensity exercise programs have been shown to improve diastolic function in patients HFPEF. High intensity interval training (HIIT) has been shown to improve diastolic function in patients with heart failure and reduced ejection fraction. However, the effects of high intensity interval training in patients with HFPEF are unknown. Fourteen patients with HFPEF were randomized to either: (1) a novel program of high-intensity aerobic interval training (n = 8), or (2) a commonly prescribed program of moderate-intensity (MOD) aerobic exercise training (n = 6). Before and after four weeks of exercise training, patients underwent a treadmill graded exercise test for the determination of peak oxygen uptake (VO2peak), a brachial artery reactivity test for assessment of endothelium-dependent flow-mediated dilation (BAFMD), aortic pulse wave velocity assessment as an index of vascular stiffness and two-dimensional echocardiography for assessment of left ventricular diastolic and systolic function. I hypothesized that (1) high-intensity aerobic interval training would result in superior improvements in FMD, aortic pulse wave velocity, VO2peak, diastolic function and, (2) changes in these parameters would be correlated with changes in VO2peak. The principal findings of the study were that a one month long high intensity interval training program resulted in significant improvements in diastolic function as measured by two-dimensional echocardiography [pre diastolic dysfunction (DD) grade - 2.13 + 0.4 vs. post DD grade - 1.25 + 0.7, p = 0.03]. The left atrial volume index was reduced in the HIIT group compared to MOD ( - 4.4 + 6.2 ml/m2 vs. 5.8 + 10.7 ml/m2, p = 0.02). Early mitral flow (E) improved in the HIIT group (pre - 0.93 + 0.2 m/s vs. post - 0.78 + 0.3 m/s, p = 0.03). A significant inverse correlation was observed between change in BAFMD and change in diastolic dysfunction grade (r = - 0.585, p = 0.028) when all the data were pooled. HIIT appears to be a time-efficient and safe strategy for improving diastolic function in patients with heart failure and preserved ejection fraction. These data may have implications for cardiovascular risk reduction in this population.
ContributorsAngadi, Siddhartha (Author) / Gaesser, Glenn A (Thesis advisor) / Mookadam, Farouk (Committee member) / Swan, Pamela (Committee member) / Vega-Lopez, Sonia (Committee member) / Lee, Chong (Committee member) / Arizona State University (Publisher)
Created2012
Description
Skeletal muscle (SM) mitochondria generate the majority of adenosine triphosphate (ATP) in SM, and help regulate whole-body energy expenditure. Obesity is associated with alterations in SM mitochondria, which are unique with respect to their arrangement within cells; some mitochondria are located directly beneath the sarcolemma (i.e., subsarcolemmal (SS) mitochondria), while

Skeletal muscle (SM) mitochondria generate the majority of adenosine triphosphate (ATP) in SM, and help regulate whole-body energy expenditure. Obesity is associated with alterations in SM mitochondria, which are unique with respect to their arrangement within cells; some mitochondria are located directly beneath the sarcolemma (i.e., subsarcolemmal (SS) mitochondria), while other are nested between the myofibrils (i.e., intermyofibrillar (IMF) mitochondria). Functional and proteome differences specific to SS versus IMF mitochondria in obese individuals may contribute to reduced capacity for muscle ATP production seen in obesity. The overall goals of this work were to (1) isolate functional muscle SS and IMF mitochondria from lean and obese individuals, (2) assess enzyme activities associated with the electron transport chain and ATP production, (3) determine if elevated plasma amino acids enhance SS and IMF mitochondrial respiration and ATP production rates in SM of obese humans, and (4) determine differences in mitochondrial proteome regulating energy metabolism and key biological processes associated with SS and IMF mitochondria between lean and obese humans.

Polarography was used to determine functional differences in isolated SS and IMF mitochondria between lean (37 ± 3 yrs; n = 10) and obese (35 ± 3 yrs; n = 11) subjects during either saline (control) or amino acid (AA) infusions. AA infusion increased ADP-stimulated respiration (i.e., coupled respiration), non-ADP stimulated respiration (i.e., uncoupled respiration), and ATP production rates in SS, but not IMF mitochondria in lean (n = 10; P < 0.05). Neither infusion increased any of the above parameters in muscle SS or IMF mitochondria of the obese subjects.

Using label free quantitative mass spectrometry, we determined differences in proteomes of SM SS and IMF mitochondria between lean (33 ± 3 yrs; n = 16) and obese (32 ± 3 yrs; n = 17) subjects. Differentially-expressed mitochondrial proteins in SS versus IMF mitochondria of obese subjects were associated with biological processes that regulate: electron transport chain (P<0.0001), citric acid cycle (P<0.0001), oxidative phosphorylation (P<0.001), branched-chain amino acid degradation, (P<0.0001), and fatty acid degradation (P<0.001). Overall, these findings show that obesity is associated with redistribution of key biological processes within the mitochondrial reticulum responsible for regulating energy metabolism in human skeletal muscle.
ContributorsKras, Katon Anthony (Author) / Katsanos, Christos (Thesis advisor) / Chandler, Douglas (Committee member) / Dinu, Valentin (Committee member) / Mor, Tsafrir S. (Committee member) / Arizona State University (Publisher)
Created2017
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Description
DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body.

DNA methylation, a subset of epigenetics, has been found to be a significant marker associated with variations in gene expression and activity across the entire human genome. As of now, however, there is little to no information about how DNA methylation varies between different tissues inside a singular person's body. By using research data from a preliminary study of lean and obese clinical subjects, this study attempts to put together a profile of the differences in DNA methylation that can be observed between two particular body tissues from this subject group: blood and skeletal muscle. This study allows us to start describing the changes that occur at the epigenetic level that influence how differently these two tissues operate, along with seeing how these tissues change between individuals of different weight classes, especially in the context of the development of symptoms of Type 2 Diabetes.
ContributorsRappazzo, Micah Gabriel (Author) / Coletta, Dawn (Thesis director) / Katsanos, Christos (Committee member) / Dinu, Valentin (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor)
Created2013-12
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Description
Obesity has developed into a worldwide health problem that is associated with many risks. The elements causing obesity are complex and numerous including behavioral, psychological, and physiological. Traditional methods of weight loss have demonstrated short-lived positive health benefits and minimal long-term weight loss, which has led to the prevalence of

Obesity has developed into a worldwide health problem that is associated with many risks. The elements causing obesity are complex and numerous including behavioral, psychological, and physiological. Traditional methods of weight loss have demonstrated short-lived positive health benefits and minimal long-term weight loss, which has led to the prevalence of bariatric surgery as an answer to long-term weight loss for Class III obesity. Gastric bypass surgery has become especially popular for its numerous benefits including successful weight loss, improvements in obesity-related diseases, and increased lifespan. Bariatric surgery is still not a perfect solution. Negative effects after surgery range from surgical complications and vitamin deficiencies to altered hormonal levels and metabolic rates. Many questions regarding bariatric surgery still remain including the impact of adolescent bariatric surgery, long-term bone effects, and long-term psychosocial and lifestyle components of bariatric patients. Understanding the good, the bad, and several of the remaining questions regarding bariatric surgery, will help health professionals be more appreciative of the complexity of treating their obese patients.
ContributorsStich, Alexandra M. (Author) / Swan, Pamela (Thesis director) / Sebren, Ann (Committee member) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
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Description
PURPOSE: Lean hypertension (HTN) is characterized by a mechanistically different HTN when compared to obese HTN. The purpose of this study is to assess whether body phenotype influences blood pressure (BP) responses following both acute and chronic exercise. METHODS: Obese (body mass index (BMI) > 30 kg/m2) and

PURPOSE: Lean hypertension (HTN) is characterized by a mechanistically different HTN when compared to obese HTN. The purpose of this study is to assess whether body phenotype influences blood pressure (BP) responses following both acute and chronic exercise. METHODS: Obese (body mass index (BMI) > 30 kg/m2) and lean (BMI < 25 kg/m2) men with pre-hypertension (PHTN) (systolic BP (SBP) 120 - 139 or diastolic BP (DBP) 80 - 89 mm Hg) were asked to participate in a two-phase trial. Phase 1 assessed differences in post-exercise hypotension between groups in response to an acute exercise bout. Phase 2 consisted of a two-week aerobic exercise intervention at 65-70% of heart rate (HR) max on a cycle ergometer. Primary outcome measures were: brachial BP, central (aortic) BP, cardiac output (CO), and systemic vascular resistance (SVR) measured acutely after one exercise session and following two weeks of training. RESULTS: There were no differences between groups for baseline resting brachial BP, central BP, age, or VO2 peak (all P > 0.05). At rest, obese PHTN had greater CO compared to lean PHTN (6.3 ± 1 vs 4.7 ± 1 L/min-1, P = 0.005) and decreased SVR compared to lean PHTN (1218 ± 263 vs 1606 ± 444 Dyn.s/cm5, P = 0.003). Average 60-minute post-exercise brachial and central SBP reduced by 3 mm Hg in Lean PHTN in response to acute exercise (P < 0.005), while significantly increasing 4 mm Hg for brachial and 3 mm Hg for central SBP (P < 0.05). SVR had a significantly greater reduction following acute exercise in lean PHTN (-223 Dyn·s/cm5) compared to obese PHTN (-75 Dyn·s/cm5, P < 0.001). In lean subjects chronic training reduced brachial BP by 4 mm Hg and central BP by 3 mm Hg but training had no effect on the BP’s in obese subjects. Resting BP reduction in response to training was accompanied by reductions in SVR within lean (-169 Dyn·s/cm5, P < 0.001), while obese experienced increased SVR following training (47 Dyn·s/cm5, P < 0.001). CONCLUSION: Hemodynamic response to both acute and chronic exercise training differ between obese and lean individuals.
ContributorsZeigler, Zachary (Author) / Swan, Pamela (Thesis advisor) / Gaesser, Glenn (Committee member) / Buman, Matthew (Committee member) / Angadi, Siddhartha (Committee member) / Farouk, Mookadam (Committee member) / Arizona State University (Publisher)
Created2016
Description
Obesity and its underlying insulin resistance are caused by environmental and genetic factors. DNA methylation provides a mechanism by which environmental factors can regulate transcriptional activity. The overall goal of the work herein was to (1) identify alterations in DNA methylation in human skeletal muscle with obesity and its underlying

Obesity and its underlying insulin resistance are caused by environmental and genetic factors. DNA methylation provides a mechanism by which environmental factors can regulate transcriptional activity. The overall goal of the work herein was to (1) identify alterations in DNA methylation in human skeletal muscle with obesity and its underlying insulin resistance, (2) to determine if these changes in methylation can be altered through weight-loss induced by bariatric surgery, and (3) to identify DNA methylation biomarkers in whole blood that can be used as a surrogate for skeletal muscle.

Assessment of DNA methylation was performed on human skeletal muscle and blood using reduced representation bisulfite sequencing (RRBS) for high-throughput identification and pyrosequencing for site-specific confirmation. Sorbin and SH3 homology domain 3 (SORBS3) was identified in skeletal muscle to be increased in methylation (+5.0 to +24.4 %) in the promoter and 5’untranslated region (UTR) in the obese participants (n= 10) compared to lean (n=12), and this finding corresponded with a decrease in gene expression (fold change: -1.9, P=0.0001). Furthermore, SORBS3 was demonstrated in a separate cohort of morbidly obese participants (n=7) undergoing weight-loss induced by surgery, to decrease in methylation (-5.6 to -24.2%) and increase in gene expression (fold change: +1.7; P=0.05) post-surgery. Moreover, SORBS3 promoter methylation was demonstrated in vitro to inhibit transcriptional activity (P=0.000003). The methylation and transcriptional changes for SORBS3 were significantly (P≤0.05) correlated with obesity measures and fasting insulin levels. SORBS3 was not identified in the blood methylation analysis of lean (n=10) and obese (n=10) participants suggesting that it is a muscle specific marker. However, solute carrier family 19 member 1 (SLC19A1) was identified in blood and skeletal muscle to have decreased 5’UTR methylation in obese participants, and this was significantly (P≤0.05) predicted by insulin sensitivity.

These findings suggest SLC19A1 as a potential blood-based biomarker for obese, insulin resistant states. The collective findings of SORBS3 DNA methylation and gene expression present an exciting novel target in skeletal muscle for further understanding obesity and its underlying insulin resistance. Moreover, the dynamic changes to SORBS3 in response to metabolic improvements and weight-loss induced by surgery.
ContributorsDay, Samantha Elaine (Author) / Coletta, Dawn K. (Thesis advisor) / Katsanos, Christos (Committee member) / Mandarino, Lawrence J. (Committee member) / Shaibi, Gabriel Q. (Committee member) / Dinu, Valentin (Committee member) / Arizona State University (Publisher)
Created2017