PURPOSE: The aim of this study was to determine if the linear and nonlinear components of the energy expenditure-walking speed relationship are influenced by body mass index (BMI; kg/m2). The secondary aims were to determine if the relationship was influenced by age, height, and sex. METHODS: Subjects (n=182) walked at 2, 3, and 4 mph for six minutes each with oxygen consumption (V̇O2; ml/kg/min) and measured via indirect calorimetry and converted to energy expenditure (EE; W/kg). Because of the curvilinear change in metabolic rate with increase in walking speed, polynomial random coefficient regression (PRCR) was employed to produce a model which captures the slope of change. Individual level linear and quadratic coefficients were analyzed for relationships with BMI, age, height, and sex. RESULTS: The net V̇O2 regression formula for walking was 1.79(x-3)2+4.97(x-3)+9.32 where x is speed in mph. BMI was modestly correlated with the quadratic coefficients (r = 0.15 to 0.17, p = 0.02 to 0.04) but not the linear coefficients (r =0.02- 0.07, p = 0.36-0.78) for V̇O2 and EE. There was no difference in coefficients between normal BMI (18.5-<25.0 kg/m2), overweight (25-<30.0 kg/m2) and obese (>30.0 kg/m2) groups (H = 1.5-4.0, p = 0.13-0.48). Delta V̇O2 for 2-3 mph, 3-4 mph, and 2-4 mph were not correlated with BMI (r = -0.02 - 0.13, p = 0.11 - 0.41). Height was inversely correlated with the linear and quadratic coefficients (r = -0.32 to -0.14, p = 0.09). Age was not correlated to coefficients (r = -0.16 to 0.32, p = 0.06-0.44). The coefficients for sex were not different after controlling for height in ANCOVA (F(1,179)=0.3-2.9, p >0.09). Age was not correlated to coefficients (r = -0.16 to –0.32, p = 0.06-0.44). CONCLUSION: Although BMI had a modest relationship with the quadratic coefficient, it explained less than 3% of the variance in V̇O2 or EE. Combined with the absence of a delta V̇O2 or a linear component, BMI does not influence the energy expenditure-walking speed relationship. Height explained up to 9% of the variance in the coefficients and eliminated apparent sex differences. Age was not related to the coefficients.

Maximal oxygen uptake (VO2max) declines with age and is a predictor of morbidity and mortality risks. Due to these implications, accurate assessment and determination of VO2max are important for the older population. Without the presence of a VO2 plateau, secondary criteria are used to determine whether the test resulted in a maximal value. However, inconsistent secondary criteria do not account for intersubject variability. To circumvent this issue, a verification phase following a traditional ramp assessment may be utilized. The purpose of this study was to compare verification phase strategies in older adults. A secondary purpose of this study was to examine the repeatability of the ramp assessment performed during each visit. Twenty-two older adults between 60 and 80 years of age were recruited to participate in the study. Each subject completed two experimental trials in a randomized, counterbalanced cross-over design. Both trials consisted of a ramp test and verification phase at either 85% (VP85) or 110% (VP110) of the peak work rate achieved during the ramp (Ramp85 and Ramp110, respectively). Expired gases and heart rate (HR) were monitored continuously and measured every ten seconds. VO2peak was determined by the highest 30-second averages for the ramp and verification phases. No significant differences were observed for absolute (L/min) VO2peak between VP85 (P = 0.679) or VP110 (P = 0.200) and the associated ramp. There was also no significant difference in maximal HR between VP85 (P = 0.243) or VP110 (P = 0.085) and the associated ramp. However, individual data shows that 36% of individuals achieved a 2% greater VO2 (L/min) during the VP85 compared to the Ramp85, while only 15% of subjects achieved a 2% greater VO2 (L/min) during the VP110 compared to Ramp110. No significant differences (P < 0.05) were found for most variables between Ramp1 and Ramp2. These data suggest that if a verification phase is employed for VO2max assessment in otherwise healthy older adults, a power slightly below peak work rate may provide a more accurate assessment compared to a power slightly above peak work rate.

The purpose of this dissertation was 1) to develop noninvasive strategies to assess skeletal muscle size, architecture, and composition in young and old adults (study #1) and 2) evaluate the impact of chemotherapeutic treatment on skeletal muscle satellite cells and capillaries (study #2). For study #1 ultrasound images were obtained from the quadriceps muscles of young (8 m, 8 f) and older (7 m, 5 f) participants on two occasions, separated by 5-15 days. Images were collected while the participants were both standing and supine, and were analyzed for muscle thickness, pennation angle, and echogenicity. In addition, test-retest reliability and ICCs were evaluated for each posture and when imaging sites remained marked or were re-measured from visit #1 to visit #2. Generally, in both younger and older adults muscle thickness was greater and echogenicity was lower in the anterior quadriceps when images were collected standing versus supine. Maintaining the imaging site between visits did not influence test re-test reliability for either age group. Older adults exhibited smaller muscle thickness, lower pennation angle and increased echogenicity. Further, variability for the use of ultrasound to determine muscle thickness and pennation angle was greater in older versus younger adults. Findings from study #1 highlight several methodological considerations for US-based assessment of skeletal muscle characteristics that should be considered for improving reproducibility and generalizability of US to assess skeletal muscle characteristics and function across the aging spectrum. This is particularly relevant given the emerging use of ultrasound to assess skeletal muscle characteristics in healthy and clinical populations. In the second study, ovariectomized female Sprague-Dawley rats were randomized to receive three bi-weekly intraperitoneal injections of the chemotherapeutic drug, Doxorubicin (DOX) (4mg/kg; cumulative dose 12mg/kg) or vehicle (VEH; saline). Animals were euthanized 5d following the last injection, and the soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected and prepared for immunohistochemical and RT-qPCR analyses. Relative to VEH, cross-sectional area (CSA) of the SOL and EDL muscle fibers were 26% and 33% smaller, respectively, in DOX animals (P<0.05). In the SOL satellite cell and capillary densities were 39% and 35% lower, respectively, in DOX animals (P<0.05), whereas in the EDL satellite cell and capillary densities were unaffected by DOX administration (P>0.05). In the SOL MYF5 mRNA expression was increased in DOX animals (P<0.05), while in the EDL MGF mRNA expression was reduced in DOX animals (P<0.05). Chronic DOX administration is associated with reduced fiber size in multiple skeletal muscles, however DOX appears to impact the satellite cell and capillary densities in a muscle-specific manner. These findings from study #2 highlight that therapeutic targets to protect skeletal muscle from DOX may vary across muscles. Collectively, these findings 1) improve the ability to examine muscle size and function in younger and older adults, and 2) identify promising therapeutic targets to protect skeletal muscle from the harmful effects of chemotherapy treatment.

Obesity prevalence is high in the United States, in part due to increased fat storage following consumption of high fat/carbohydrate (sugar) foods. Following a meal, carbohydrate stimulates its own oxidation, while simultaneously suppressing fat oxidation, ultimately leading to fat storage. Aerobic exercise preceding a meal increases fat oxidation in the postprandial period, which may reduce fat storage. The ideal exercise prescription for optimal postprandial fat oxidation is unknown. The effect of low and moderate intensity continuous exercise (MIE) has been studied extensively, while the effects of high-intensity interval exercise (HIIE) on post-prandial substrate oxidation has not been examined. The purpose of this study was to compare the effects of MIE and HIIE on postprandial substrate oxidation after consumption of an isocaloric meal (2 glazed donuts; 520 kcal) in healthy adults. Ten subjects (8 males, 2 females; age=24yr, BMI=24 kg/m2) completed three conditions in random order: 1) no exercise control; 2) MIE: cycling at 60-75%HRmax; 3) HIIE: cycling at 90-95%HRmax. The duration of each exercise bout was sufficient to expend approximately 520 kcal, the energy equivalent of the donuts, which were consumed 1 hour post-exercise. Immediately after consuming the donuts, pulmonary ventilation and gas exchange were measured breath-by-breath continuously and recorded (min-by-min) for 5 hours. Repeated measures analysis of covariance was used to compare the mean differences in outcome variables accounting for gender. Absolute postprandial fat oxidation (g/5 hours) was 17.3±5.4, 27.1±9.6 and 23±1.2 for control, MIE and HIIE trials respectively, with the postprandial fat oxidation significantly greater for the two exercise conditions compared to control. Relative to baseline values, both exercise conditions resulted in cumulative net postprandial fat oxidation significantly greater than control (control = -1.79±3.99g; MIE = 11.51±8.41g, HIIE= 9.51±5.20g). Therefore, results indicate that exercise most certainly increases postprandial fat oxidation, and that exercise type, either MIE or HIIE, is not as important as total energy expended. The fact that exercise of ~1 hour was required to oxidize the amount of fat in two donuts, that required only a few minutes to consume, highlights the challenges of using exercise for weight control in an obesogenic environment.

Cardiovascular disease and diabetes are major health burdens. Diabetes is a primary risk factor of cardiovascular disease, and there is a strong link between obesity and risk of developing diabetes. With the prevalence of prediabetes highest among overweight/obese individuals, investigation into preventative strategies are needed. Aerobic exercise is a potent stimulus for both insulin and non-insulin dependent glucose uptake into the skeletal muscle. A single exercise session can improve insulin sensitivity within hours after exercise. The effects of intensity, type, and volume of exercise on glucose homeostasis have been studied extensively; however, controlling for muscle contraction frequency with a constant exercise intensity and workload has not been examined. The purpose of this study was to compare muscle contraction frequency during aerobic exercise by altering cycling cadence on insulin sensitivity and vascular health. Eleven obese males (age=28yr, BMI=35kg/m2) completed three conditions in random order: 1) control-no exercise; 2) 45-min cycling at 45 revolutions per minute (45RPM) at 65-75%VO2max; 3) 45-min cycling at 90RPM at 65-75%VO2max. Glucose control and insulin sensitivity were assessed with oral glucose tolerance tests (OGTT) 4 hours post-exercise. Vascular health was assessed via flow-mediated dilation (FMD) pre-exercise, 1-hr and 2-hr post exercise and ambulatory blood pressure was assessed pre-exercise, and continually every 15 min post-exercise. Linear mixed models were used to compare the mean differences in outcome variables. There were no significant differences found between control and both exercise conditions for all OGTT outcomes and no differences were found between control and exercise in FMD (all, p>0.05). Significant effects for exercise were found for both brachial and central blood pressure measures. Brachial systolic blood pressures were lower at 2- and 4-hr post-exercise by approximately -10 and -8mmHg, respectively (p<0.001 and p=0.004) versus control. Central systolic blood pressures were lower at 2-, 3-, and 4-hr post-exercise by approximately -8, -9 and -6mmHg, respectively (p<0.001, p=0.021 and p=0.004) versus control. In conclusion, aerobic exercise, regardless of muscle contraction frequency, were unable to effect glucose control and insulin sensitivity. Similarly, there was no effect on vascular function. However, there was a significant effect of aerobic exercise on reducing post-exercise blood pressure.

The winter holiday period has been highlighted as a major risk period for weight gain due to excess caloric intake in the form of fat and sugar. Furthermore, diets high in fat and sugar have been implicated in the pathogenesis of diabetes and cardiovascular disease. Exercise aids in the prevention of weight/fat gain, and prevents deleterious changes in cardiometabolic function. The objective of this study was to examine the effects of a fat-sugar supplemented diet, with and without two different exercise training protocols, on body composition, glycemic control and other markers of cardiovascular disease in an at-risk population of overweight and obese males. Twenty-seven, healthy overweight/obese (BMI >25 kg/m2) males were fed 2 donuts per day, 6 days/week, for four weeks, while maintaining their current diet. In addition, all subjects were randomized to one of the following conditions: sedentary control, 1,000 kcal/week moderate-intensity continuous training (MICT) (50% of peak oxygen consumption), or 1,000 kcal/week high-intensity interval training (HIIT) (90-95% of peak heart rate). Supervised exercise training was performed 4 days/week on a cycle ergometer. Changes in body weight and composition, endothelial function, arterial stiffness, glycemic control, blood lipids and cardiorespiratory fitness (CRF) were assessed before and after the intervention. Body weight, lean mass and visceral fat increased significantly in HIIT (p<0.05) and were unchanged in MICT. There was a trend for a significant increase in body weight (p=0.07) and lean mass (p=0.11) in control. Glycemic control during the 2-h OGTT improved significantly in MICT and control, with no change in HIIT. Hepatic insulin resistance index (IRI) and 30-min insulin during the OGTT improved significantly after MICT and worsened following control (p=0.03), while HIIT was unchanged. CRF increased significantly in both HIIT and MICT, with no change in control (p<0.001). There were no significant changes in other markers of cardiovascular disease. The addition of a fat-sugar supplement (~14,500 kcal) over a 4-week period was not sufficient to induce deleterious changes in body composition and cardiometabolic health in overweight/obese young males. Exercise training did not afford overweight/obese males additional health benefits, with the exception of improvements in fitness and hepatic IRI.

Background: Postprandial hyperglycemia can increase levels of oxidative stress and is an independent risk factor for complications associated with type 2 diabetes.

Purpose: To evaluate the acute effects of a 15-min postmeal walk on glucose control and markers of oxidative stress following a high-carbohydrate meal.

Methods: Ten obese subjects (55.0 ± 10.0 yrs) with impaired fasting glucose (107.1 ± 9.0 mg/dL) participated in this repeated measures trial. Subjects arrived at the laboratory following an overnight fast and underwent one of three conditions: 1) Test meal with no walking or fiber (CON), 2) Test meal with 10g fiber and no walking (FIB), 3) Test meal with no fiber followed by a 15-min treadmill walk at preferred walking speed (WALK). Blood samples were taken over four hours and assayed for glucose, insulin, thiobarbituric reactive substances (TBARS), catalase, uric acid, and total antioxidant capacity (TAC). A repeated measures ANOVA was used to compare mean differences for all outcome variables.

Results: The 2hr and 4hr incremental area under the curve (iAUC) for glucose was lower in both FIB (2hr: -93.59 mmol∙120 min∙L-1, p = 0.006; 4hr: -92.59 mmol∙240 min∙L-1; p = 0.041) and WALK (2hr: -77.21 mmol∙120 min∙L-1, p = 0.002; 4hr: -102.94 mmol∙240 min∙L-1; p = 0.005) conditions respectively, compared with CON. There were no differences in 2hr or 4hr iAUC for glucose between FIB and WALK (2hr: p = 0.493; 4hr: p = 0.783). The 2hr iAUC for insulin was significantly lower in both FIB (-37.15 μU ∙h/mL; p = 0.021) and WALK (-66.35 μU ∙h/mL; p < 0.001) conditions, compared with CON, and was significantly lower in the WALK (-29.2 μU ∙h/mL; p = 0.049) condition, compared with FIB. The 4hr iAUC for insulin in the WALK condition was significantly lower than both CON (-104.51 μU ∙h/mL; p = 0.001) and FIB (-77.12 μU ∙h/mL; p = 0.006) conditions. Markers of oxidative stress were not significantly different between conditions.

Conclusion: A moderate 15-minute postmeal walk is an effective strategy to reduce postprandial hyperglycemia. However, it is unclear if this attenuation could lead to improvements in postprandial oxidative stress.

The effects of aging on muscular efficiency are controversial. Proponents for increased efficiency suggest that age-related changes in muscle enhance efficiency in senescence. Exercise study results are mixed due to varying modalities, ages, and efficiency calculations. The present study attempted to address oxygen uptake, caloric expenditure, walking economy, and gross
et cycling efficiency in young (18-59 years old) and older (60-81 years old) adults (N=444). Walking was performed at three miles per hour by 86 young (mean = 29.60, standard deviation (SD) = 10.50 years old) and 121 older adults (mean = 66.80, SD = 4.50 years old). Cycling at 50 watts (60-70 revolutions per minute) was performed by 116 young (mean= 29.00, SD= 10.00 years old) and 121 older adults (m = 67.10 SD = 4.50 years old). Steady-state sub-maximal gross
et oxygen uptake and caloric expenditures from each activity and rest were analyzed. Net walking economy was represented by net caloric expenditure (kilocalories/kilogram/min). Cycling measures included percent gross
et cycling efficiency (kilo-calorie derived). Linear regressions were used to assess each measure as a function of age. Differences in age group means were assessed using independent t-tests for each modality (alpha = 0.05). No significant differences in mean oxygen uptake nor walking economy were found between young and older walkers (p>0.05). Older adults performing cycle ergometry demonstrated lower gross
et oxygen uptakes and lower gross caloric expenditures (p< 0.05).

In adults, consuming a high-fat meal can induce endothelial dysfunction while exercise may mitigate postprandial endothelial dysfunction. Whether exercise is protective against postprandial endothelial dysfunction in obese youth is unknown. The purpose of this study was to determine if high-intensity interval exercise (HIIE) performed the evening prior to a high-fat meal protects against postprandial endothelial dysfunction in obese adolescent males. Fourteen obese adolescent males (BMI%tile=98.5±0.6; 14.3±1.0yrs) completed the study. After initial screening, participants arrived, fasted at 9:00 in the morning where brachial artery flow-mediated dilation (FMD) was measured using duplex ultrasound after 20min of supine rest (7.0±3.0%) and completed a maximal exercise test on a cycle ergometer (VO2peak=2.6±0.5 L/min). Participants were randomized and completed 2 conditions: a morning high-fat meal challenge with evening prior HIIE (EX+M) or a morning high-fat meal challenge without prior exercise (MO). The EX+M condition included a single HIIE session on a cycle ergometer (8 X 2min at ≥90%HRmax, with 2min active recovery between bouts, 42min total) which was performed at 17:00 the evening prior to the meal challenge. In both conditions, a mixed-meal was tailored to participants body weight consisting of 0.7g of fat/kg of body weight consumed (889±95kcal; 65% Fat, 30% CHO). FMD was measured at fasting (>10hrs) and subsequently measured at 2hr and 4hr after high-fat meal consumption. Exercise did not improve fasting FMD (7.5±3.0 vs. 7.4±2.8%, P=0.927; EX+M and MO, respectively). Despite consuming a high-fat meal, FMD was not reduced at 2hr (8.4±3.4 vs. 7.6±3.9%; EX+M and MO, respectively) or 4hr (8.8±3.9 vs. 8.6±4.0%; EX+M and MO, respectively) in either condition and no differences were observed between condition (p(condition*time)=0.928). These observations remained after adjusting for baseline artery diameter and shear rate. We observed that HIIE, the evening prior, had no effect on fasting or postprandial endothelial function when compared with a meal only condition. Future research should examine whether exercise training may be able to improve postprandial endothelial function rather than a single acute bout in obese youth.

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.