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Item Open Access Acute beet juice ingestion improves estimates of insulin sensitivity in obese adults(Colorado State University. Libraries, 2014) Beals, Joseph William, author; Bell, Christopher, advisor; Hickey, Matthew, committee member; Gentile, Christopher, committee memberPoor glucose regulation is strongly associated with low nitric oxide (NO) bioavailability; a characteristic that may be improved with stimulation of NO generating pathways. For example, endothelial nitric oxide synthase null mice demonstrate improved glucose metabolism following sodium nitrate ingestion. Dietary nitrates are sequentially reduced in the oral and gastric cavities to NO, a process that is attenuated by rinsing with an antibacterial mouthwash. We hypothesized that acute dietary nitrate consumption will improve glucose tolerance. 9 sedentary, healthy, obese adults (2 male; body mass index: 33.7 ± 4.0 kg/m2: age: 45±7 years; mean ± SE) were studied. Using a randomized crossover design, four oral glucose tolerance tests were performed (equal carbohydrate load). To assess the influence of dietary nitrate, subjects consumed either 500mL of beet juice + 25g glucose, or 500mL of water + 75g glucose, with and without prior antibacterial mouthwash use. Beet juice was selected because it is rich in nitrate. Venous blood samples were collected for the determination of glucose and insulin concentrations. Neither the circulating glucose nor insulin responses were influenced by beet juice and/or mouthwash (P>0.05). However, the Matsuda Index, an estimate of insulin sensitivity, was greater for beet juice compared with beet juice preceded by mouthwash (104.6 ± 11.7 vs. 83.5 ± 11.1; P<0.05). These preliminary data suggest that acute dietary nitrate ingestion may promote insulin sensitivity in obese adults.Item Open Access Adjusting attitudes about altitude: novel approaches to promote human performance in high-altitude(Colorado State University. Libraries, 2014) Scalzo, Rebecca Lynn, author; Bell, Christopher, advisor; Hamilton, Karyn L., advisor; Miller, Benjamin F., committee member; Kanatous, Shane B., committee memberMilitary personnel frequently operate in environmental extremes, such as high-altitude, without adequate time for acclimatization. Altitude mediated decrements in human physiological function jeopardize mission success and personal safety. The following dissertation describes three experiments directed at the identification of non-traditional, military specific approaches to promote human functional performance in high-altitude. The specific aims of the following experiments were: 1) to compare the difference in time trial performance in normoxia and hypoxia following oral administration of a placebo, a non-specific phosphodiesterase inhibitor/adenosine receptor antagonist (Aminophylline), a carbonic anhydrase inhibitor (Neptazane), or the combination of Aminophylline and Neptazane; 2) to assess endurance exercise performance in hypoxia following an intravenous infusion of glucose with and without prior sympathetic nervous system inhibition (clonidine); and 3) to determine endurance exercise performance in hypoxia following a high-carbohydrate meal with and without prior/concurrent administration of an oral insulin sensitizer (metformin) and to compare hypoxic endurance exercise performance with endurance exercise performance in normoxia following the same meal. When compared with normoxia, hypoxia attenuated endurance exercise performance in these experiments. In experiment 1, we found that concomitant administration of Aminophylline and Neptazane attenuated the hypoxia-mediated deficit in endurance exercise performance compared with placebo. Neither Aminophylline nor Neptazane alone ameliorated this decrement. In experiment 2, prior clonidine administration attenuated the cardiovascular response to hypoxia assessed by heart rate and blood pressure responses at rest but did not deleteriously impact endurance exercise performance in hypoxia. Finally, the preliminary data from experiment 3 suggest metformin improved the metabolic response to a high-carbohydrate meal in hypoxia, and potentially augmented skeletal muscle glycogen synthesis. Endurance exercise performance was unaffected in hypoxia following metformin administration. Collectively, the data from these experiments suggest these pharmacological treatments, compatible with military specific demands, effectively promote human physiological function in high-altitude.Item Open Access Caffeine augments the lactate and interleukin-6 response to moderate-intensity exercise in males but not females(Colorado State University. Libraries, 2022) Abbotts, Kieran Shay Struebin, author; Bell, Christopher, advisor; Hamilton, Karyn, committee member; Melby, Christopher, committee memberThe release of interleukin (IL)-6 from contracting skeletal muscle is thought to contribute to some of the health benefits bestowed by exercise. This IL-6 response appears proportional to exercise volume. Unfortunately, high volumes of exercise are not feasible for all people. Caffeine augments the magnitude of increase in circulating concentration of IL-6 in response to high-intensity and long-duration exercise, in males. Caffeine is also known to increase circulating concentrations of lactate during exercise. One of the mechanisms thought to contribute to IL-6 release from exercising skeletal muscle is lactate production. We hypothesized that caffeine, ingested prior to moderate-intensity exercise, would lead to greater circulating concentrations of lactate and IL-6 in a study population comprising both males and females. 15 healthy adults (9 males and 6 females, aged 26±7 years, (mean ± SD)) completed 30-minutes of moderate-intensity cycle ergometer exercise, equivalent to the ventilatory threshold, after ingesting either caffeine (6 mg/kg) or placebo. Arterialized-venous blood was collected throughout each of the exercise sessions. Compared with placebo, caffeine increased end-exercise circulating concentrations of lactate (5.72±3.95 vs. 7.14±4.66 mmol/L, P<0.001) but not end-exercise IL-6 (1.84±0.97 vs. 2.37±1.04 pg/mL, P=0.139). However, when females were excluded from the analysis, caffeine augmented (P=0.04) the magnitude of increase of end-exercise IL-6 concentration (1.80±0.86 vs. 2.57±1.21 pg/mL); this effect was further exaggerated after 30-minutes of inactive recovery (3.81±2.32 vs. 5.06±3.22 pg/mL). Noteworthy, caffeine evoked greater end-exercise lactate concentrations in data sets containing only males (P=0.02) and only females (P=0.002) but did not influence the IL-6 response in females (P=0.94). Our preliminary data imply that in males unable/unwilling to perform high-intensity and/or long-duration exercise, caffeine may potentially enhance the IL-6 mediated health benefits of relatively short, moderate-intensity exercise.Item Open Access Combining curcumin and alpha-lipoic acid to treat cardiometabolic syndrome(Colorado State University. Libraries, 2015) Binns, Scott Edward, author; Bell, Christopher, advisor; Ryan, Elizabeth, committee member; Hickey, Matthew, committee memberINTRODUCTION: Obesity is associated with increased risk of developing cardiometabolic disease characterized by decreased insulin sensitivity, positive energy balance, and cardiovascular disease. Separately, the dietary compounds curcumin (CUR) and alpha lipoic acid (ALA) increase energy expenditure and insulin sensitivity. However the efficacy of combined CUR and ALA supplementation to improve characteristics of cardiometabolic health in overweight humans has never been evaluated. METHODS: 11 overweight and sedentary adults were randomly assigned to a placebo (n=5; age: 44 ± 8 years; body mass index: 31.9 ± 2.1 kg/m²; VO₂peak: 26.8 ± 4.1 ml/kg/min; (mean ± SE)) or CUR+ALA (n=6; age: 38 ± 7 years; body mass index: 32.2 ± 1.2 kg/m²; VO₂peak: 24.9 ± 3.7 ml/kg/min) 12-week intervention. Measurements of resting metabolic rate (RMR) and thermic effect of feeding (TEF) via indirect calorimetry, and insulin sensitivity via the hyperinsulinemic euglycemic clamp technique were assessed in a pre/post treatment manner. Additionally, resting blood pressure, and body composition via dual energy x-ray absorptiometry (DEXA) were measured. RESULTS: 12-weeks of CUR+ALA supplementation did not change RMR (1467 ± 89.9 to 1539 ± 94.4 kcal/day; P=0.239) or TEF AUC (P=0.51). Additionally, no change in glucose infusion rate occurred as a result of supplementation (12.8 ± 2.1 to 12.4 ± 1.2 mg/FFM kg/min; P=0.690). Resting systolic blood pressure was unaffected in the CUR+ALA group (116 ± 3.2 to 123.8 ± 25.4 mmHg; P=0.31). Body fat percentage did not change with CUR+ALA supplementation (43.8 ± 2.2 to 41.6 ± 1.9 body fat percent; P=0.162), however, body fat percentage decreased in all subjects regardless of treatment (P=0.002). DISCUSSION: These preliminary data do not support the use of CUR+ALA to improve metabolic and cardiovascular health in overweight adults.Item Open Access Comparison of five oral cannabidiol preparations in adult humans: pharmacokinetics, body composition, and heart rate variability(Colorado State University. Libraries, 2021) Williams, Natasha N. Bondareva, author; Bell, Christopher, advisor; Weir, Tiffany, committee member; LaRocca, Tom, committee memberData supporting the physiological effects of cannabidiol (CBD) ingestion in humans are conflicting. Differences between CBD preparations and bioavailability may contribute to these discrepancies. Further, an influence of body composition on CBD bioavailability is feasible, but currently undocumented. The aims of this study were to: (1) compare the pharmacokinetics of five oral CBD preparations over 4 hours; (2) examine the relationship between body composition and CBD pharmacokinetics; and, (3) explore the influence of CBD on heart rate variability. In total, five preparations of CBD, standardized to 30 mg, were administered orally to 15 healthy men and women (21–62 years) in a randomized, crossover design. Prior to and 60 min following CBD ingestion, heart rate variability was determined. Body composition was assessed using dual energy X-ray absorptiometry. Peak circulating CBD concentration, time to peak concentration, and area under the curve was superior in a preparation comprising 5% CBD concentration liquid. Fat free mass was a significant predictor (R2 = 0.365, p = 0.017) of time to peak concentration for this preparation. Several heart rate variability parameters, including peak frequency of the high frequency band, were favorably, but modestly modified following CBD ingestion. These data confirm an influence of CBD preparation and body composition on CBD bioavailability, and suggest that acute CBD ingestion may have a modest influence on autonomic regulation of heart rate.Item Open Access Effect of short-term epigallocatechin-3-gallate supplementation on the thermic effect of feeding and resting metabolic rate(Colorado State University. Libraries, 2009) Lonac, Mark Charles, author; Bell, Christopher, advisor; Hickey, Matthew S., committee member; Nelson-Ceschin, Tracy L., committee member; Melby, Christopher L., committee memberThe sympathetic nervous system (SNS) both provides tonic support of resting metabolic rate (RMR) and mediates approximately one-third of the thermic effect of feeding (TEF), the latter accounting for ~10% of daily energy expenditure. Epigallocatechin-3-gallate (EGCG), the most abundant and bioactive catechin in green tea, inhibits the catecholamine-degrading action of the enzyme catechol-O-methyltransferase, thereby prolonging SNS activation. Accordingly, we hypothesized that short-term EGCG supplementation would augment RMR and TEF in healthy adult humans. METHODS: Sixteen subjects reported to our lab on two mornings (≥ 10 days apart) after 12 hours without food, caffeine, and alcohol and 24 hours without exercise. Each visit followed double-blinded, randomized EGCG or cornmeal placebo supplementation (seven pills over 48 hours, 135 mg EGCG/pill). RMR and respiratory exchange ratio (RER) were determined using the ventilated hood technique for 45 minutes prior to consumption of a liquid mixed-composition meal providing calories equivalent to 40% of RMR. Energy expenditure (EE) and RER were then measured for the first 20 of every 30 minutes for five hours. RESULTS: All subjects (n = 9 males, n =7 females; age 25 ± 2 yrs, mean ± s.e.; 22.6 ± 1.8% body fat) were weight stable and were washed out from prior green tea or EGCG use for ≥ one month. Results are reported as placebo vs. EGCG. EGCG did not affect RMR or baseline RER (RMR: 1665 ± 84 vs. 1610 ± 89 kcal/day; p = 0.10; RER: 0.82 ± 0.01 vs. 0.83 ± 0.01; p = 0.29). EGCG did not affect the area under the TEF response curve, expressed as absolute postprandial EE (441,083 ± 22,436 vs. 429,350 ± 24,209 arbitrary units, A.U.; p = 0.22) or the absolute (58,104 ± 5,297 vs. 58,949 ± 5,672 A.U.; p = 0.88) or percentage (3,508 ± 263 vs. 3,647 ± 285 A.U.; p = 0.67) difference between absolute postprandial EE and baseline RMR. No differences between placebo and EGCG were observed for RER during TEF. CONCLUSION: These results indicate that, contrary to our hypothesis, short-term EGCG supplementation does not influence RMR or TEF in healthy adults. This suggests that reported positive benefits of green tea on energy balance are the result of increased physical activity EE and/or decreased energy intake.Item Open Access Fatigue resistance vs. fall resistance: high-intensity interval training and the dissociation of stamina and stability in older adults(Colorado State University. Libraries, 2016) Brodsky, Timothy William, author; Bell, Christopher, advisor; Reiser, Raoul, committee member; Malcolm, Mattew, committee memberINTRODUCTION: The population of older adults (≥65 years) in the U.S. is growing, and this population faces unique health risks compared to young and middle aged adults. One of the primary health risks for older adults is falling, which is the leading cause of preventable death and injury within this population. Traditional exercise interventions have been effective in reducing fall risk but require significant time commitment. High-intensity interval training (HIIT) requires less time commitment than traditional exercise training and may be a viable alternative to reduce fall risk among older adults. METHODS: 13 sedentary young (n=7, 4 female; age: 21±1 (mean ± SE)) and older (n=6, 2 female; age; 69±2) adults completed 9 sessions of HIIT over 3 weeks. Balance at rest and after a single bout of HIIT was measured via center-of-pressure (COP) measures, fatigue resistance via a time to exhaustion (TTE) test, maximal aerobic capacity (VO2max) via indirect calorimetry and peak power output via Wingate test. All variables were assessed before and after training. RESULTS: Short-term HIIT had no effect on balance at rest or following a single bout of HIIT. TTE was greater in both young (25.8±4.0 vs. 37.0±3.1 min) and older (31.5±3.9 vs. 54.0±8.8 min) adults after training (p<0.05). VO2max was also greater after training (+1.8 ml/kg/min, p<0.05) in both groups. Peak power output during HIIT was greater after training in young (p<0.001) but not in older adults. CONCLUSION: These data do not support HIIT as an effective intervention for reducing fall risk in older adults. Three weeks of HIIT improves fatigue resistance but not balance, indicating a dissociation between stamina and stability in young and older adults.Item Open Access Influence of exercise modality and modality-specific training on endurance exercise performance in hypoxia(Colorado State University. Libraries, 2017) Theisen, Jeremy Kenneth, author; Bell, Christopher, advisor; Dinenno, Frank, committee member; Kanatous, Shane, committee memberINTRODUCTION: In hypoxia, endurance exercise performance is impaired. The magnitude of impairment may be variable between individuals and exercise modalities. The purpose of this study was to determine the influence of exercise modality and modality-specific training on hypoxia-mediated performance decrements. METHODS: In a randomized cross-over design, endurance trained cyclists (4 males, 3 females) and rowers (5 males, 3 females) performed exercise on both cycling and rowing ergometers. On separate occasions, participants completed graded exercise tests in normoxia (FiO2= 0.21), and standardized exercise (15 minutes, 100 W) and time trials (4 km cycling, 2 km rowing) in normoxia and hypoxia (FiO2= 0.15). RESULTS: Hypoxia-mediated performance decrements were not different between cyclists and rowers (17±1 vs. 18±1%, p=0.189), cycling and rowing (18±2 vs. 16±2%, p=0473), or any combination of training or test modality (p=0.138). In rowers, peripheral oxygen saturation (SpO2) was lower at the end of rowing compared to cycling time trials (78±1 vs. 83±1%, p=0.002), and lower than that of cyclists at the end of rowing time trials (78±1 vs. 83±1%, p<0.001). DISCUSSION: Hypoxia-mediated performance decrements were not different between training modalities, test modalities, or any combination of the factors. We speculate that reduced SpO2 in rowers at the end of rowing time trials may be related to a greater active muscle mass, causing a rightward shift in the oxyhemoglobin dissociation curve and reduced transit time of blood in pulmonary capillaries. In conclusion, SpO2 may be related to active muscle mass during exercise and could potentially modulate performance in hypoxia.Item Open Access Liposomal encapsulated alpha-lipoic acid, benfotiamine and curcumin prevent overfeeding mediated increases in waist circumference(Colorado State University. Libraries, 2017) Grimm, Nathan Carlisle, author; Bell, Christopher, advisor; Dooley, Gregory, committee member; Hickey, Matthew, committee memberINTRODUCTION: To determine if liposomal (L) encapsulated alpha-lipoic acid (0.5g), benfotiamine (0.5g) and curcumin (2.0g) (ABC) would prevent the unfavorable metabolic consequences of sedentary high-fat overfeeding in healthy young adults. METHODS: 29 young (18-30 years), healthy, physically active men and women were randomly assigned to ingest placebo (n=9), ABC (n=10), or L-ABC (n=10) twice daily for 28 days. Between days 22 and 28 all participants abstained from their normal regular exercise and consumed a high calorie, high fat diet. RESULTS: On Day 29, circulating alpha lipoic acid was greater (p<0.01) in L-ABC (412±73 ng/mL) compared with ABC (154±33 ng/mL). During the sedentary high fat overfeeding, dietary intake was not different (p>0.60) between groups (~3,400 kcal/day; ~50% from fat). Sedentary high fat overfeeding increased (p<0.05) waist circumference in the placebo (+2.7±2.7 cm) and ABC (+3.3±2.0) groups but not the L-ABC group (+0.7±2.7). The magnitudes of increase (p<0.05) in body mass (1.7±0.3 kg), fat mass (0.7±0.2 kg), and blood pressure (3±1 mmHg) and decrease (p<0.05) in insulin sensitivity (Matsuda Index: -2.9±0.9) after overfeeding were not different between groups (all p>0.50). DISCUSSION: Liposomal encapsulated alpha-lipoic acid, benfotiamine and curcumin: 1) promoted alpha-lipoic acid bioavailability; and, 2) prevented sedentary high-fat overfeeding mediated increases in waist circumference in usually active healthy young adults. These data may have important public health implications for periods of inactive overconsumption such as during seasonal celebrations.Item Embargo Neuromuscular electrical stimulation: getting amped up to prevent exercise resistance(Colorado State University. Libraries, 2024) Bomar, Matthew Charles, author; Bell, Christopher, advisor; Perry, Richard, committee member; Stephens, Jaclyn, committee memberPurpose: Exercise resistance (ER) is characterized by the absence of exercise induced improvements in fat metabolism following a meal. The prolonged sedentary behavior between successive workouts is what contributes to this lack of health improvements typically associated with exercise. The suggested energy expenditure (EE) threshold for avoiding ER is the equivalent of walking ~8,500 steps/day. Population data indicate that the typical adult walks 5,000 steps/day. Neuromuscular Electrical Stimulation (NMES) evokes skeletal muscle contractions and increases EE. This study aims to determine the feasibility of using NMES to increase total daily EE by the equivalent of 3,500 steps, thereby meeting the theoretical threshold sufficient to prevent ER. Methods: Fourteen recreationally active males and females (7/7) underwent measures of resting EE, with and without NMES, and EE while walking 8,500 steps on a treadmill. The duration of NMES sufficient to increase EE to match 3,500 steps was calculated, and then verified with measures of EE while walking 5,000 steps after a bout of NMES. Results: Bland–Altman statistics of agreement were used to assess concordance between the EE associated with walking 8,500 steps (286 ± 64 kcal; mean ± SD), and the EE associated with walking 5,000 steps after NMES (293 ± 65 kcal). The mean difference between the EE values was 7 kcal, and the 95% limits of agreement were -39 to 53 kcal. Implications: These preliminary data suggest NMES can be used to increase total daily EE by the equivalent of 3,500 steps, thereby meeting the theoretical threshold to prevent ER.Item Open Access Pharmacokinetic investigation of commercially available edible marijuana products in humans: potential influence of body composition and influence on glucose control(Colorado State University. Libraries, 2021) Ewell, Taylor, author; Bell, Christopher, advisor; Hickey, Matthew, committee member; Hamilton, Karyn, committee member; Weir, Tiffany, committee memberOur investigation of five commercially available edible marijuana products containing 10mg of delta-9-tetrahydrocannabinol (THC) aimed to describe the pharmacokinetics of these products, investigate the potential influence of body composition on THC bioavailability, and, based on epidemiological research completed in the last decade, determine if acute marijuana ingestion influences glucose tolerance when compared to a THC-free gummy. We studied seven regular marijuana users. We utilized a single-blind randomized controlled crossover study design in which participants self-administered edible marijuana or a THC-free gummy. Thirty minutes following marijuana ingestion a standard oral glucose tolerance test was initiated via consumption of a 75g glucose drink. There was, at minimum, a four-day washout period between trials. Average time to peak plasma THC concentration ranged from 35 to 90 minutes, and average peak THC concentrations ranged from 3.2 to 5.5 ng/ml. Significant differences between products were identified twenty- and thirty-minutes post-ingestion. Several measures of body composition had significant correlations with plasma THC, although none of these correlations persisted across all products. There were no differences in indices of glycemic control between marijuana products or the THC-free gummy. Following acute edible marijuana ingestion in habitual users, significant differences in THC pharmacokinetics existed between similar products, possibly due to body composition, although glucose control was not impacted. In summary, these data may inform recreational users to the proper dose for marijuana ingestion to achieve the desired outcome and to avoid overdose.Item Open Access Short-term sprint-interval training improves insulin sensitivity in young adult humans(Colorado State University. Libraries, 2009) Johnson, Tyler Kass, author; Bell, Christopher, advisor; Hickey, Matthew S., advisor; Miller, Benjamin F., committee member; Melby, Christopher L., committee memberHabitual endurance exercise has been shown repeatedly to increase insulin sensitivity, one of the principal determinants of blood glucose control. Many adults however, choose not to participate in this type of exercise, citing insufficient time as a perceived obstacle. A recent study has described improved blood glucose control post-consumption of a glucose beverage following 2-weeks of sprint-interval training (SIT), implying that SIT may increase insulin sensitivity. PURPOSE: Using the gold standard measure, the hyperinsulinemic euglycemic clamp technique, we investigated the hypothesis that SIT will increase insulin sensitivity. METHODS: 12 healthy, sedentary or recreationally active adults (age: 27 ± 3 yr; body mass index: 26.2 ± 1.4 kg/m2; VO2peak: 36.0 ± 3.3 ml/kg/min (mean ± SE)) completed 6 sessions of repeated (4 to 7) 30-second bouts of extremely high-intensity cycle ergometer exercise (i.e. a Wingate protocol) over 14 days. Prior to and 72 hours following completion of SIT the glucose infusion rate (GIR) required to maintain a blood glucose concentration of 90 mg/dL during a standardized infusion of insulin was determined. In order to quantify the effect of the most recent SIT bout on insulin sensitivity, GIR was determined in 7 adults (25 ± 1 yr; 25.7 ± 1.4 kg/m2; 37.1 ± 4.3 ml/kg/min) prior to and 72 hours following a single bout of SIT. Finally, in order to establish the day-to-day variability in GIR, 9 adults (23 ± 2 yr; 26.8 ± 1.6 kg/m2, 33.3 ± 2.2 ml/kg/min) served as a sedentary control. RESULTS: Compared with baseline, insulin sensitivity was increased following short-term SIT (GIR: 6.2 ± 0.7 vs. 8.0 ± 0.8 mg/kg/min; P = 0.02) but was unchanged following a single bout of SIT (9.7 ± 1.3 vs. 10.7 ± 1.4; P = 0.43) or a period of inactivity (7.9 ± 0.9 vs. 8.3 ± 1.0; P = 0.38). Regardless of intervention, blood glucose concentration at the end of the hyperinsulinemic euglycemic clamp, body mass and fasting blood glucose concentration remained unchanged (all P > 0.2), with the exception of a small increase in fasting glucose following a single bout of SIT (73.6 ± 1.8 vs. 75.8 ± 1.3 mg/dL; P = 0.01). CONCLUSION: These data, collected using the gold standard hyperinsulinemic euglycemic clamp technique, suggest that short-term SIT is a viable alternative to endurance training as a strategy to improve insulin sensitivity.Item Open Access Sprint interval training: the influence of exercise modality(Colorado State University. Libraries, 2013) Giordano, Gregory Robert, author; Bell, Christopher, advisor; Hickey, Matthew, committee member; Melby, Christopher, committee memberSprint interval training (SIT), whether performed on a cycle ergometer or non-motorized treadmill, enhances exercise capacity and evokes favorable metabolic and cardiopulmonary adaptations. However, despite known differences between cycling and running, the influence of exercise modality on the adaptive response to SIT has not been directly addressed. Additionally, the effect of SIT on the angiogenic factors, pigment epithelial-derived factor (PEDF) and vascular endothelial growth factor (VEGF), has not been well characterized. PURPOSE: To examine the influence of exercise modality on the adaptive response to SIT, we compared the effects of SIT performed on one of three different exercise machines: non-motorized treadmill, cycle ergometer, or plyometrics platform. Additionally, we sought to characterize the changes in circulating and skeletal muscle PEDF and VEGF following three weeks of SIT. METHODS: Twenty-seven healthy, sedentary or recreationally active adults (age: 23 ± 5 years; body mass index: 25.7 ± 4.7 kg m-2; VO2peak: 36.7 ± 6.1 ml kg-1 min-1 (mean ± SE)) completed nine sessions of repeated (four to eight) 30-s bouts of maximal exercise on a non-motorized treadmill (RUN), cycle ergometer (CYC), or plyometrics platform (JMP) over 21 days. Prior to and following completion of SIT, peak oxygen uptake (VO2peak) and time to exhaustion at 80% VO2peak were measured. Additionally, blood and skeletal muscle was sampled prior to and following completion of SIT to measure PEDF and VEGF. RESULTS: Three weeks of SIT increased time to exhaustion (40.0 min ± 3.2 vs.51.3 ± 5.5 min, P = 0.006). The interaction with exercise modality did not achieve statistical significance (P = 0.08), however, it appears that time to exhaustion increased in the RUN (43.2 ± 5.2 vs. 57.4 ± 9.2 min) and CYC (41.7 ± 6.1 vs. 62.3 ± 11.6 min) groups, but not the JMP group (35.5 ± 5.6 vs. 35.0 ± 4.9 min). Circulating and skeletal muscle VEGF and PEDF were not altered by three weeks of SIT (P > 0.05). DISCUSSION: Independent of exercise modality, three weeks of SIT improves endurance exercise capacity and does not alter circulating or skeletal muscle PEDF or VEGF.Item Open Access Sympathetic inhibition attenuates hypoxia induced insulin resistance in healthy adult humans(Colorado State University. Libraries, 2012) Peltonen, Garrett Lee, author; Bell, Christopher, advisor; Miller, Benjamin F., committee member; Hamilton, Karyn L., committee member; Gentile, Christopher L., committee memberAcute and chronic exposure to hypoxia is known to decrease insulin sensitivity in healthy humans and animals, while simultaneously increasing the activity of the sympathetic nervous system (SNS). Likewise, obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are clinical conditions characterized by hypoxia, elevated SNS activity, and a high prevalence of insulin resistance. In contrast to hypoxic exposure and hypoxic related diseases, hyperoxia (FIO2 = 1.00) has been shown to improve insulin sensitivity while concomitantly decreasing SNS activity. Consistent with this, continuous positive airway pressure (CPAP), a common OSA treatment, has proven effective in abolishing nocturnal bouts of intermittent hypoxia, enhancing insulin sensitivity and diminishing SNS activity. Although the underlying mechanism of hypoxia induced insulin resistance remains unclear, it appears that elevated SNS activity may be a mediating factor. Therefore, we hypothesized that inhibition of the SNS would attenuate hypoxia induced insulin resistance. METHODS: 10 males (23±1 years, body mass index 24.2±0.8 kg/m2 (mean±SE)) reported to our laboratory on 4 separate mornings, separated by a minimum of 7 days, after a 12-hour fast and 48-hour abstention from exercise. Insulin sensitivity was determined via the hyperinsulinemic euglycemic clamp technique under each of the following conditions: normoxia (FIO2=0.21), hypoxia (FIO2=0.11), normoxia and SNS inhibition (48-hour transdermal clonidine administration (Catapres-TTS; 0.2mg/day)), and hypoxia SNS inhibition. RESULTS: Oxyhemoglobin saturation was decreased (P<0.01) during hypoxia (63±2%) compared to normoxia (96±0%) and there was no significant effect of SNS inhibition on oxyhemoglobin saturation in either normoxia or hypoxia (P>0.25). Norepinephrine was elevated in hypoxia (137±13%; P=0.02), as determined by area under curve and expressed relative to normoxia. SNS inhibition prevented the hypoxia induced increase in norepinephrine (94±14%; P=0.43). The glucose infusion rate (adjusted for fat free mass and circulating insulin), required to maintain blood glucose at 90 mg/dl (5 mmol/L) during administration of insulin, was decreased during hypoxia (128±30 nmol/kg fat free mass/pmol/L/min; P=0.03) compared to normoxia (225±23) and remained unchanged during normoxia and SNS inhibition (219±19; P=0.86), and hypoxia and SNS inhibition (169±23; P=0.23). CONCLUSION: Inhibition of the SNS attenuates hypoxia induced insulin resistance.Item Open Access The influence of Dapagliflozin on dietary mediated physiological and behavioral changes(Colorado State University. Libraries, 2019) Ryan, Shane P. P., author; Bell, Christopher, advisor; Melby, Christopher, committee member; Braun, Barry, committee memberThe diabetes medication, Dapagliflozin, is a sodium-glucose co-transporter 2 (SGLT2) inhibitor. The mechanism of action is decreasing renal absorption of glucose, leading to glucosuria, and modest weight loss. We hypothesized that SGLT2 inhibition would potentiate the favorable influence of dietary counseling on body composition and physiological adaptations in overweight or obese adults. Fifty sedentary overweight/obese men (n = 12) and women (n = 38) were randomly assigned to 12 weeks of dietary counseling for weight loss, supplemented with daily ingestion of either placebo or Dapagliflozin (up to 10 mg/day); coded as Pill A and Pill B. Dietary counseling consisted of weekly, one-on-one, 30-minute meetings targeting modest calorie restriction. Before and after treatment, body composition, resting metabolic rate (RMR), insulin sensitivity, appetite and satiety were measured. Twelve weeks of dietary counseling decreased (P < 0.049) body mass, fat mass, and RMR; neither variable was influenced by pill assignment (interaction: P > 0.264). Dietary counseling also decreased lean mass (treatment main effect: P < 0.001), however the decrease in lean mass was greater in Pill B than in Pill A (interaction: P = 0.037). Neither dietary counseling nor SGLT2 inhibition influenced insulin sensitivity (P > 0.055). Overall, 12-weeks of dietary counseling leads to favorable modification of body mass and fat mass regardless of pill assignment. However, Pill A appears to reduce the dietary counseling mediated loss in lean mass. Except for lean mass, the effects of dietary counseling for weight loss were not influenced by SGLT2 inhibition.Item Open Access Vitamin C supplementation: a comparison of delivery methods and the ability to attenuate oxidative stress induced by ischemia-reperfusion(Colorado State University. Libraries, 2015) Davis, Janelle Lynn, author; Bell, Christopher, advisor; Hamilton, Karyn, committee member; Frye, Melinda, committee memberIntravenous delivery of vitamin C to adult humans decreases indices of oxidative stress and in some instances improves physiological function. Oral delivery of vitamin C is more practical than intravenous but typically results in lower circulating vitamin C concentrations. The hypotheses for this study were, oral consumption of vitamin C encapsulated in liposomes would: 1) result in higher circulating vitamin C concentrations than a traditional oral supplement, and 2) better attenuate oxidative stress induced by ischemia-reperfusion. Eleven overweight/obese adults [age: 52±7 years; body mass index: 34.1±1.0 kg/m²; mean±SE] were administered a 4 g supplement of placebo, or vitamin C via different delivery methods, on four separate occasions, in a random order. The four treatments were: placebo, oral vitamin C, liposomal vitamin C, and intravenous (IV) administration of vitamin C. Concentrations of ascorbic acid, thiobarbituric acid reactive substances (TBARS), and oxidized low-density lipoproteins (Ox-LDL) were measured in venous blood at baseline, and over four hours following supplement administration. At three hours a blood pressure cuff was placed around the upper arm and inflated to 200 mmHg for 20 minutes to evoke an ischemia-reperfusion injury. Plasma ascorbic acid concentrations were significantly greater after IV vitamin C compared with all other treatments at all time points (P<0.01). At two hours, all subsequent ascorbic acid concentrations were greater after liposomal vitamin C treatment compared with oral vitamin C and placebo treatments. Plasma ascorbic acid concentrations were greater after oral vitamin C compared with placebo (P<0.01). Neither vitamin C nor ischemia-reperfusion influenced Ox-LDL. In the placebo condition, ischemia-reperfusion increased plasma TBARS concentration; all of the vitamin C treatments prevented this increase. These data suggest that liposomal encapsulation of vitamin C increases bioavailability of oral vitamin C. Additionally, the antioxidant protection provided by liposomal vitamin C is not inferior to intravenously administered vitamin C.Item Open Access What goes down need not go back up: decreasing the biological drive toward weight regain by increasing energy flux(Colorado State University. Libraries, 2014) Paris, Hunter Louis Ross, author; Bell, Christopher, advisor; Melby, Christopher, committee member; Hickey, Matthew, committee memberINTRODUCTION: Weight regain after weight loss is the experience of most obese dieters. Metabolic adjustments characterized by decreased resting metabolic rate (RMR) and increased hunger can prevent long-term success. Possibly this energy gap could be attenuated by a high flux (HF) state (higher expenditure coupled with higher intake). METHODS: 6 obese adults [age (mean±SE) = 42±12 y; body mass index (BMI)=35.7±3.7 kg/m2] underwent 7% diet-induced weight loss and were stabilized at this weight for 3 weeks. RMR via indirect calorimetry, and hunger via visual analog scale were then examined during two 4-day conditions of energy balance in random order--Low Flux (LF): sedentary with energy intake (EI)=RMR x1.35; and HF: daily exercise net energy cost of ~500 kcal/d and EI= RMR x1.7. RESULTS: Average 5-day weight did not differ between HF (103.4±4.7 kg) and LF (103±4.8 kg) (P>0.10). Average daily RMR was higher during HF (1926±138 kcal/day) compared to LF (1847±126 kcal/day; P = 0.05). Resting fat oxidation was also higher during HF (0.073+0.010 g/min) compared to LF (0.059+0.012 g/min; P<0.05). Average daily, perceived end-of-day hunger was lower during HF compared to LF (P<0.05). CONCLUSION: These preliminary data suggest that compared to a sedentary LF state of energy balance, a HF energy balance state is associated with a greater RMR, resting fat oxidation, and less hunger - all of which may attenuate the energy gap and protect against weight regain.