Endurance exercise capacity is a powerful predictor of health status. Having low levels of endurance exercise capacity has been linked with cardiovascular disease. Variation in endurance exercise capacity, measured during a graded exercise test, has been reported across cross-section, twin, and family studies. This variation is evidence of a genetic component to the phenotype of endurance exercise capacity: however, the genetic factors responsible for explaining this variation are undefined, in part because previous research has been performed on a limited scale. Therefore, three sets of experiments were designed to identify: 1) Novel quantitative trait loci (QTL) for endurance exercise capacity in 34 strains of inbred mice using genome-wide association mapping. 2) The effect of chromosome substitution on endurance exercise capacity using linkage analysis in F2 mice. 3) The effect of chromosome substitution on endurance exercise capacity using wild-derived mice. The main findings of this dissertation are: 1) There are strain-specific differences in endurance exercise capacity across 34 strains of male inbred mice. Genome-wide association mapping identified novel putative QTL on chromosomes 2, 7, 11, and 13. 2) Linkage analysis identified a novel QTL on chromosome 14 at the 56 cM position for run time and work. Linkage analysis also identified a potential sex-specific QTL, with the identified QTL significant for male mice only. 3) Novel putative QTL were identified on chromosomes 3 and 14 in chromosome substitution mice from wild-derived mice. These data suggest that chromosome 14 is an important contributor to the genetic regulation of intrinsic endurance exercise capacity. These studies support a genetic component to endurance exercise capacity by identifying strain-specific differences and novel, putative QTL.

Master of Science / Department of Kinesiology / Steven W. Copp / Cancer patients have a reduced exercise capacity compared to age-matched healthy counterparts which contributes to premature fatigue. The reductions in exercise capacity are multifactorial and vary depending on the type of treatments and the specific cancer. Given that cancer treatments have been shown to impair cardiovascular and/or skeletal muscle function, it is difficult to determine if cancer itself reduces exercise capacity. We used a rat prostate tumor model to test the hypothesis that cancer independently reduces endurance exercise capacity. Methods: In male Copenhagen rats (COP/CrCrl), an initial treadmill test to exhaustion was used to determine endurance exercise capacity. Subsequently, the prostates of the rats were injected with either prostate carcinoma cells (R-3327 AT-1) in Matrigel (cancer: n = 9) or Matrigel only (sham: n = 7). Treadmill tests to exhaustion were repeated four and eight weeks post-surgery. Results: Time to exhaustion decreased over the course of the experimental protocol in both the sham and cancer groups. However, the overall reduction in time to exhaustion in the cancer group (-16.7 ± 1.9 min) was significantly greater (p = 0.038) than the sham group (-10.1 ± 2.2 min). Despite no differences in total body mass at the end of the experimental protocol, heart, left ventricle, and gastrocnemius muscle mass were significantly lower in the cancer group compared to the sham group (p < 0.05 for all). Moreover, within the cancer group heart and left ventricle mass, but not gastrocnemius mass, were significantly inversely correlated with prostate tumor mass. Conclusion: Endurance exercise capacity was reduced in rats with untreated prostate cancer to a greater extent than it was reduced in sham operated rats. Although multiple mechanisms likely contributed to the reduced exercise capacity, reductions in heart and gastrocnemius muscle mass likely played an important role.

Two times are critical for the horse ¾ the first few days of its life and the last few moments of a race. Vitamin E is critical in regard to immune competence in the first and antioxidant status in the latter. Studies conducted at the Middleburg Agricultural Research and Extension (MARE) Center include the development of horse feeds that replace sugar and starch with fat and fiber. The previous fat source of the pasture supplement under development was corn oil, which contains much vitamin E, was replaced with a cereal by product, which contains relatively little. Vitamin E has been studied in horses to a limited degree but not in grazing Thoroughbreds, thus the MARE Center gave me the opportunity to study vitamin E in Thoroughbred mares and foals. Middleburg is located in the Blue Ridge Mountains on Northern Virginia close to the site of one of the toughest endurance races in the world. This allowed me the opportunity to study vitamin E and antioxidant status in the horse during endurance racing. Initial studies of vitamin E supplementation to mares during the last trimester of gestation were disconcerting with no changes in serum concentrations of a-tocopherol (vitamin E). Studies conducted during the post-partum period revealed evidence of responses to vitamin E supplementation, as increased a-tocopherol concentrations were observed in mares' milk and in foal serum. Foals are born with virtually no circulatory antibodies and the supplementation of a synthetic form of vitamin E to mares demonstrated an increased passive transfer of immunoglobulins to foals. Natural vitamin E has shown a greater bioavailability than synthetic forms, in other species and was tested here at the MARE Center on mares. A greater passive transfer of immunoglobulins was observed with natural vitamin E supplementation compared with the synthetic forms, with immunoglobulin M concentrations in foal serum remaining higher for a longer period after birth compared to foals of non-supplemented mares. The transfer of a-tocopherol via the milk was also increased in concentration and duration in mares supplemented with natural vitamin E. Bioavailability of five oral forms of vitamin E (3 natural and 2 synthetic) were tested and one natural form was also administered intravenously so that clearance of vitamin E could be used to calculate the efficiency of absorption of the oral forms. Efficiency of absorption for oral treatments was not determined because of the slow turnover time of the intravenously administered vitamin E, which confounded all subsequent baseline serum a-tocopherol concentrations. Of the salvageable data, serum a-tocopherol concentrations were higher in grouped treatments at 9 and 12 h post dosing. Lipid fractions revealed possible insufficient absorption of the oral doses of vitamin E and possibly tissue saturation following intravenous doses of vitamin E. Serum concentrations of a-tocopherol were generally higher following natural forms of oral vitamin E administration. As vitamin E is the most important antioxidant in cells, it is often supplemented to endurance horses competing in 80 and 160 km races. Vitamin E protects lipid cell membranes from peroxidation by free radicals, which are increased during strenuous exercise resulting in oxidative stress. The antioxidant status of horses is severely tested during endurance racing and so a study was conducted to monitor changes in circulating antioxidants during three endurance races. Interesting novel findings in the horse were the maintenance of serum a-tocopherol and the depletion of erythrocyte glutathione and plasma ascorbate during two 80 km and one 160 km races. Associations were found between increased muscle cell enzyme leakage and decreased antioxidant status during endurance exercise and although associations do not prove a causation of oxidative stress, they do provide motivation to search for a cause and it is tempting to propose that oxidative stress damaged muscle cell membranes in endurance horses. Further, these findings propose a connection between muscle cell damage and a new form of exertional rhabdomyolysis (ER) that has been observed in endurance horses, where oxidative fibers are damaged compared to the typical glycolytic fiber damage associated with known forms or ER. An increased understanding of vitamin E utilization in the horse will improve the health and welfare of all horses, but especially newborn foals and the athletic endurance horses. / Ph. D.

Effects of potassium supplementation were evaluated in four studies in endurance horses during races and treadmill exercise. In the first and second studies a potassium-free experimental formula was compared to potassium rich commercial formulas. The first study showed that supplementation increased plasma [K+], and that the extra sodium in the potassium-free experimental formulas helped to attenuate acidosis at the end of the ride. In the second study supplementation also increased plasma [K+], however speeds were lower and no increases were observed in plasma concentrations during the race. Supplementation of potassium during recovery helped to restore plasma [K+]. Higher plasma [Ca++] was found in horses supplied with experimental feeds, due to a lower dietary cation anion balance (DCAB). Three eliminated horses had heart rate arrhythmias and labile heart rates accompanied with higher plasma [K+] and lower [Ca++] than finishers. Also horses supplied with the experimental sodium-rich formula were less dehydrated than the ones receiving commercial formulas. The third study involved an 80 km endurance exercise test on the treadmill, and plasma [K+] was affected by potassium supplementation during exercise and recovery. The supply of potassium caused higher plasma [K+] helping to restore body stores. Also chloride supply in the electrolyte formulas maintained plasma [Cl-] levels during exercise and affected plasma concentrations during recovery. The fourth study showed that potassium supply affects plasma concentration, but also increases lactate production and glucose during sub-maximal exercise. A potassium-free electrolyte supply caused higher plasma [Ca++] during exercise. Higher sodium supply in the potassium-free electrolytes improved hydration during exercise. These studies show that potassium should supplemented after exercise and but not be done during exercise because of the risk of increased neuromuscular excitability. / Ph. D.

Doctor of Philosophy / Department of Human Nutrition / Mark D. Haub / Maximizing performance and results in competitive events is something that all athletes strive to achieve. Nutritional strategies have been developed to best optimize the likelihood of success in competitive events. While dietary protein was classically believed to be the key macronutrient in exercise performance, overwhelming evidence now supports the role of maximizing carbohydrate intake and availability in endurance performance. The role of carbohydrate intake prior to, during and after endurance exercise has been heavily studied and relevant literature will be discussed herein. This paper consists of three chapters and a summary related to carbohydrate intake and performance outcomes in endurance sports. While nutritional status surrounding the endurance events is discussed, this paper focuses on the ergogenic and metabolic effects of carbohydrates during the endurance bout. Chapter one serves as a literature review of carbohydrate administration during endurance exercise. Types of carbohydrates, their role as substrates in liver and skeletal muscle during exercise, and their effects on endurance performance are discussed. The role of carbohydrate on central factors of fatigue and motor output also are covered. Chapter two addresses the role of multiple carbohydrate supplements on cycling performance. The role of these supplements on blood glucose, insulin, lactate, and IGFBP-1 also are discussed. Chapter three addresses the effect of nutritional status prior to exercise on the ability of a carbohydrate mouth rinse to impart a performance enhancing effect. There were no treatment effects (p>0.05) of the type carbohydrate ingested, compared with placebo, on selected metabolic and performance outcomes. Likewise, there was no ergogenic effect of mouth rinsing, in the fasted or fed state, in moderately trained endurance cyclists.

The purpose of this study was to investigate the effects of hydroxytyrosol (HT) supplementation on markers of mitochondrial biogenesis, aerobic capacity, and endurance exercise performance in recreationally active men. Sixty-one (n = 61) subjects (21.46 ± 0.22 yrs, 179.46 ± 0.79 cm, 78.91 ± 1.19 kg) consumed either a high dose (HI) HT supplement (150 mg HT), a low dose (LO) HT supplement (50 mg HT), or a placebo (PLA) every day for 6 weeks. Muscle biopsies from the vastus lateralis were obtained at baseline and after 6 weeks of supplement consumption and analyzed for markers of mitochondrial biogenesis: succinate dehydrogenase (SDH), citrate synthase (CS), and peroxisome proliferator-activated receptor ɣ coactivator (PGC)-1α. Subjects completed exercise testing on a bicycle ergometer at baseline and after 3 and 6 weeks of supplement consumption to measure changes in maximal aerobic power (VO2MAX), lactate threshold, respiratory exchange ratio (RER), substrate utilization, and endurance exercise performance on a 20 km time trial course. The primary findings were that HT supplementation increased muscle oxidative enzyme activity suggesting increased oxidative capacity. HT also increased time trial performance at midpoint and endpoint and this corresponded with an improvement in lactate threshold and a lower RER for the LO HT treatment. Time trial performance was also improved at endpoint for PLA, however, unlike LO an HI HT, this was accompanied by a significant increase in rating of perceived exercise (RPE) and not associated with improvements in muscle oxidative capacity. Our results indicate that HT ranging from 50 to 150 mg/day for 6 weeks can improve muscle oxidative capacity and aerobic performance, and suggests that HT may be used chronically to improve mitochondrial function. HT may be used as an effective means to increase mitochondria to improve exercise performance, and limit diseases associated with mitochondrial dysfunction such as cardiovascular disease, type II diabetes, and some cancers. / text

The purpose of this study was to investigate the effects of 6 weeks of hydroxytyrosol (HT) supplementation on markers of muscle damage in healthy, recreationally active men before and throughout acute aerobic exercise bouts. Using a randomized, double-blind, repeated-measures, placebo-controlled design, sixty-one (n = 61) subjects (21.46 ± 0.22 yrs, 179.46 ± 0.79 cm, 78.91 ± 1.19 kg) consumed either a high dose (HI) HT supplement (150 mg HT), a low dose (LO) HT supplement (50 mg HT), or a placebo (PLA) every day for 6 weeks. Throughout the course of the study, the subjects performed four time trial rides (TT1-TT4) on a cycle ergometer. TT1 occurred before supplementation, TT2 halfway through the supplementation period, and TT3 and TT4 occurred in the sixth week and final two days of supplementation. Blood was drawn prior to (pre) and just before termination (end) of each time trial to measure markers of muscle damage during exercise. We observed that endurance exercise increased indicators of muscle damage, CPK and myoglobin, but an association between HT treatment and reduced muscle damage indicators during exercise were not demonstrated. However, the HT supplementation for 6 weeks in recreationally-active males improved time trial performance in the HT treatment groups over the course of the study and this improvement was accompanied by a lower increase in myoglobin concentration in blood in the HI treatment group than in the LO treatment group. Also, performance was improved after 6 weeks in the PLA group. This improvement was associated with an increase in rating of perceived exertion (RPE). RPE was not increased in either the LO and HI treatment groups, although time trial performance was significantly improved. It is possible that HT can improve performance by altering perception of effort. We conclude that chronic and acute HT supplementation did not reduce markers of muscle damage in this population at rest, during, or following exercise, but improved aerobic performance. / text

Endurance athletes have long benefited from ingesting carbohydrates prior to, and during endurance events. Fatigue during endurance exercise has repeatedly been associated with the depletion, or reduction, of bodily carbohydrate reserves. The improved endurance capability observed after aerobic training has, however, been attributed to the increased oxidation of fat relative to carbohydrate, thereby having a 'carbohydrate sparing" effect and thus delaying the point at which reduced carbohydrate reserves will cause fatigue. This study was therefore designed to investigate the effects of medium-chain triglyceride (MCT) and carbohydrate (CHO) supplementation, on the performance and metabolic parameters of nine male marathon athletes. These results were then statistically compared to the effects of adding L-carnitine to the MCT and CHO supplement, on the same parameters. Metabolic parameters included nutritional status evaluations, serum organic acid profiles (non-esterified fatty acid and L-lactate profiles), and plasma carnitine determinations. Performance was measured in terms of peak treadmill running speed, V02 max, respiratory exchange ratios, heart rates, vco2 and vo2 data during progressive treadmill exercise tests. Nutrition and energy intakes were recorded during the study, as well as record kept of the athlete's training programmes. At the end of each supplementation period, a standard marathon was included in the experimental design, in order to practically validate controlled laboratory results. The main findings of this study included the identification of two athletes as 'fat burners'~ Non-esterified fatty acid (NEFA) profiles indicated that they predominantly relied on fatty acid oxidation during exercise, after MCT supplementation. The latter presumably because of adaptive changes in their metabolism, enabling them to benefit from MCT supplementation. In spite of the majority of athletes relying on carbohydrate metabolism during exercise, the addition of L-carnitine to the MCT and CHO supplement, induced a shift towards lipid metabolism; evident from RER and VC02 data, as well as the majority of athletes improving their performance. The observed shift was slight; the latter being ascribed to the relatively small dose of L-carnitine (compared to previous studies) included in the supplement. However, L-carnitine was incorporated into a palatable, liquid MCT and CHO supplement, and not merely administered in the form of a pharmacological dose. A major, and extremely unexpected finding, was the presumed effect that the winter, and continuous cold exposure, had on plasma carnitine levels. Plasma carnitine levels decreased significantly, without any intervention, prior to the start of the second trial period, which stretched over the middle of winter. Despite carnitine supplementation, plasma carnitine levels still decreased. This occurrence most certainly influenced results; the shift towards lipid metabolism would presumably have been more pronounced, had the 'Winter factor' not come into play. / Dissertation (MSc)--University of Pretoria, 2012. / Physiology / unrestricted

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第21133号 / 農博第2259号 / 新制||農||1057(附属図書館) / 学位論文||H30||N5107(農学部図書室) / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 保川 清, 教授 金本 龍平, 准教授 井上 和生 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Exercise is known to induce changes in the gut, typically referred to as the ‘forgotten organ’, and changes in gut microbiota can also occur with exercise possibly imparting systemic benefits. The question remains whether or not microbiota from an exercised animal can independently affect skeletal muscle morphology. Our first objective was to examine whether an endurance exercise program could modify the microbiota in donor mice. Second, we aimed to elucidate if such an endurance-trained microbiota could be transferred to germ-free mice via fecal inoculation. Finally, we sought to determine how the morphology and functional characteristics of skeletal muscle were influenced as a result of fecal inoculation. We hypothesized that germ-free mice recipients inoculated with the microbiota from endurance trained donors would undergo morphological changes in muscle fibre type composition and physiological changes in skeletal muscle function associated with a more oxidative phenotype. Eight-week-old male C57BL/6NCrl donor mice (n = 20) were randomized into two groups: one group completed an endurance exercise training protocol on a treadmill machine 3x/week for 11 weeks (n = 10) while one group remained cage-bound (n = 10). Ten-week-old male (n = 7) and female (n = 9) germ-free mice were colonized with the cecal microbiota of the donor mice in that, equal numbers of germ-free mice were inoculated with exercised-microbiota as sedentary-microbiota. Glucose metabolism and performance measures were evaluated in the donors as well as the recipients post-inoculation. Muscle tissue was extracted for immunohistochemistry and mitochondrial assays. During the intra-peritoneal glucose tolerance test (IPGTT), significant differences in blood glucose were found at 30min between exercise-inoculated and sedentary-inoculated (23.4 ± 2.2; 29.0 ± 1.9 mmol/L, p<0.05).and change in blood glucose relative to baseline (12.04 ± 2.4; 18.3 ± 1.9 mmol/L, p<0.01). There were significant sex-based differences in the blood glucose response in inoculated animals such that there were significant differences in blood glucose between the exercise-inoculated females and sedentary-inoculated females at 15mins (28.4 ± 2.4; 30.6 ± 1.1 mmol/L, p<0.05) and 30mins (24.7 ± 3.6; 29.9 ± 2.4 mmol/L, p<0.01), however no differences between exercise-inoculated males and sedentary-inoculated males. In addition, there were significant differences in the change in blood glucose relative to baseline between the exercise-inoculated females and sedentary-inoculated females at 15mins (12.3 ± 1.9; 20.6 ± 0.8 mmol/L, p<0.01) and 30mins (10.2 ± 2.6; 19.9 ± 2.1 mmol/L, p<0.001). This novel characterization of a link between gut microbiota and skeletal muscle suggests a transmissible capacity of microbiota to impart properties of ‘healthy’ muscle into compromised populations. / Thesis / Master of Science (MSc) / The gut microbiome or microbiota describes the composition of the human gut – remarkably, over 100 trillion bacterial cells live in symbiosis with the cells of the human body. Research from the past decade has elucidated the salient nature of the human gut microbiome on immunity, metabolic homeostasis, and overall health and disease. Transformative research in the field has demonstrated the ability to transfer these bacterial colonies from one individual to another and elicit change, such as altering body mass and adiposity, respective to their donor. The interaction between gut microbiota and other organ systems i.e. brain, liver, adipose tissue has been the focus of several recent investigations, suggesting that lifestyle changes such as diet and exercise can influence communication between the gut and various other organs and contribute to changes in function. Skeletal muscle is the largest muscle in the human body accounting for 40% of total mass and although the main role of skeletal muscle is locomotion and postural stabilization, it is integral for the regulation of blood glucose as well as a reservoir for other macronutrients. Acute and chronic physical exercise cause a myriad of adaptive responses throughout the human body including in skeletal muscle and the gut. Therefore, the existence and influence of a gut-muscle link or ‘axis’ on human health cannot be ignored. What is unclear exactly, is if exercise-induced adaptations in the gut of an individual can be transferred to elicit change in the gut of a recipient and further induce adaptations at the level of the skeletal muscle.