Effects of a Short Work/Shorter Rest Intermittent Exercise on Muscle Metabolic Status, VO2, Hemoglobin Saturation and Performance, PhD, 2010, Glen Robert Belfry, Exercise Science, University of Toronto. Abstract Many sports require short duration work periods and short duration rest periods (INT). This dissertation examines the engagement of aerobic and anaerobic energy systems in acute exercise with brief (10 seconds) work and recovery (5 seconds) and the effect of chronic exposure on those systems. The differences between INT and continuous exercise (CONT) of deoxygenated hemoglobin saturation (ΔHHb), the pattern of breath-by-oxygen uptake (VO2) and muscle metabolic status, including, [Pi], [Pi]/[PCr], and [H+] were studied in young healthy adults. The physiological and performance responses to a four week, 12 session cycle ergometer training regime of the CONT and INT protocols were observed. Fluctuations in VO2, ∆HHb, [PCr], and [H+] were observed within the work : recovery duty cycle of INT. Fluctuations of VO2, ΔHHb, and [PCr] may be a function of the priming effects of previous high intensity exercise, inhibition at the locus of metabolic control, and elevated blood flow over the recovery-work transitions. Fluctuations in oxidative phosphorylation were associated with concurrent fluctuations in [PCr]. [Pi] and [PCr] were greater in INT vs CONT, whereas no differences were observed for [H+] between conditions. Reduced [PCr] may be the most appropriate indicator of metabolic stress, not increased [Pi] or [H+]. Similar improvements in aerobic power were observed for CONT and INT training, whereas anaerobic performance was enhanced post-INT training. Collectively the findings indicate that a unique INT exercise protocol facilitates increased muscle blood flow versus continuous exercise, the temporal association of muscle metabolic status, ΔHHb, and pulmonary VO2 with work rate, the apt use of [PCr] as a proxy for metabolic stress, and when this unique INT bout is utilized as a training protocol, adaptations in both aerobic and anaerobic metabolism will occur.

Effects of a Short Work/Shorter Rest Intermittent Exercise on Muscle Metabolic Status, VO2, Hemoglobin Saturation and Performance, PhD, 2010, Glen Robert Belfry, Exercise Science, University of Toronto. Abstract Many sports require short duration work periods and short duration rest periods (INT). This dissertation examines the engagement of aerobic and anaerobic energy systems in acute exercise with brief (10 seconds) work and recovery (5 seconds) and the effect of chronic exposure on those systems. The differences between INT and continuous exercise (CONT) of deoxygenated hemoglobin saturation (ΔHHb), the pattern of breath-by-oxygen uptake (VO2) and muscle metabolic status, including, [Pi], [Pi]/[PCr], and [H+] were studied in young healthy adults. The physiological and performance responses to a four week, 12 session cycle ergometer training regime of the CONT and INT protocols were observed. Fluctuations in VO2, ∆HHb, [PCr], and [H+] were observed within the work : recovery duty cycle of INT. Fluctuations of VO2, ΔHHb, and [PCr] may be a function of the priming effects of previous high intensity exercise, inhibition at the locus of metabolic control, and elevated blood flow over the recovery-work transitions. Fluctuations in oxidative phosphorylation were associated with concurrent fluctuations in [PCr]. [Pi] and [PCr] were greater in INT vs CONT, whereas no differences were observed for [H+] between conditions. Reduced [PCr] may be the most appropriate indicator of metabolic stress, not increased [Pi] or [H+]. Similar improvements in aerobic power were observed for CONT and INT training, whereas anaerobic performance was enhanced post-INT training. Collectively the findings indicate that a unique INT exercise protocol facilitates increased muscle blood flow versus continuous exercise, the temporal association of muscle metabolic status, ΔHHb, and pulmonary VO2 with work rate, the apt use of [PCr] as a proxy for metabolic stress, and when this unique INT bout is utilized as a training protocol, adaptations in both aerobic and anaerobic metabolism will occur.

Abstract:Introduction: Ageing is associated with a decrease in physical capacity. However, various aspects of this phenomenon remain to be clarified. In the present project, we aimed to investigate age-induced changes in physical capacity, metabolic status, and inflammation in men and women, and to investigate potential correlations between physical capacity and inflammation and/or metabolic markers.Material and method: 39 men and 36 women were longitudinally evaluated at four time points at 16, 34, 52, and 63 years of age. Muscle strength was measured by functional tests such as bench press, handgrip, vertical jump, two hand lift, and curl up. The Åstrand test was performed to estimate maximal oxygen uptake (VO2max). Muscle thickness was also determined using ultrasonography. Inflammatory and metabolic blood parameters were also measured.Results: Muscle strength tended to decrease at old ages and was generally higher in men than women according to muscle function tests. At the age of 63, men displayed significantly higher muscle mass and strength compared to women. Insulin, glucose, and high-density lipoprotein (HDL) significantly increased during the period from 52 to 63 years of age. Total cholesterol, low-density lipoprotein (LDL), and HDL displayed a sex-dependent trend, as they had higher values among women. Glucose, on the other hand, was greater in male individuals. Neither time- nor sex-dependent changes were found in hemoglobin A1C (HbA1C) and/or C-reactive protein (CRP). Muscle function tests were negatively correlated with HbA1C, insulin, total cholesterol, and CRP at the age of 63. VO2max also showed negative correlations with HbA1C and insulin at the age of 52 and with glucose at the ages of 52 and 63. In other words, increased HbA1C and insulin at the age of 52 as well as increased glucose at the ages of 52 and 63 were associated with decreased VO2max.Conclusion: Alterations in physical capacity were similar between men and women during aging. High inflammatory markers (CRP), as well as dysregulated metabolic status, seem to be somewhat associated with deteriorated muscle function at old ages.

Undernutrition and oxidative stress in fetal life and infancy may lead to adverse health outcomes in the offspring. We studied nutrition and oxidative parameters in pregnancy and their associations with birth anthropometry and metabolic status in the children. In Matlab in rural Bangladesh, women were randomized to either early (Early) invitation to food supplementation or to start at their own liking (Usual). Women were also allocated to either; 1) 60 mg iron and 400 µg folic acid (Fe60F), 2) multiple micronutrients including 30 mg iron and folic acid (MMS), or 3) 30 mg iron and folic acid (Fe30F). Micronutrients (hemoglobin, iron, zinc, folic acid, vitamin B-12) were assessed in pregnancy week 14, lipid peroxidation in week 14 and 30, and DNA oxidation in week 19. The offspring were assessed for anthropometric measurements at birth and metabolic status at 4.5 years. Micronutrient deficiencies were common with zinc and vitamin B-12 deficiency being most prevalent. Anemia was present in approximately one third of women, however, iron deficiency was uncommon seen in only 2%. Maternal Early food supplementation group resulted in an improved lipid status in the children at 4.5 years compared to Usual food group. Prenatal use of MMS lowered the children’s glucose, insulin, HOMA-IR, and growth factors compared to Fe60F.   Lipid peroxidation in early pregnancy was associated with size at birth and insulin and HOMA-IR levels in the children. Lipid peroxidation in late pregnancy, however, was associated with the children’s lipid status. Both increasing lipid peroxidation and increasing DNA oxidation was associated with decreasing IGF-1 levels.  The beneficial effects of an Early start of food supplementation show that an improved prenatal nutrition may have lasting effects in the offspring and highlights the importance of early timing food supplementation. Use of MMS, however, resulted in lower insulin levels, which, considering the already low level of insulin in these children, may be a cause of concern. MMS also resulted in growth factors indicative of slower growth and further research appears to be needed before scaling up the use of MMS. Oxidative parameters in pregnancy were associated with longer-term outcomes in the offspring, suggesting that oxidative stress may be involved in the development of later metabolic disease.

No description available.

A espermatogênese é um processo orquestrado e coordenado pelo qual os espermatozoides são produzidos. Ao final deste processo, o excesso de citoplasma presente nas espermátides é fagocitado, permanecendo um resíduo denominado de gota citoplasmática. Os espermatozoides em fase de maturação apresentam gota, que migra da região proximal para regiões mais distais da célula espermática. Estudos relacionam o remanescente citoplasmático à proteção antioxidante e à ativação metabólica de espermatozoides imaturos. Os mecanimos fisiológicos da maturação e os status oxidativo e metabólico em células epididimárias de bovinos são pobremente elucidados. Desta forma, foram realizados dois experimentos com o objetivo de caracterizar o status oxidativo e metabólico de espermatozoides bovinos durante a maturação espermática, e os possíveis papéis da gota citoplasmática envolvidas nesse processo. Para tal, amostras espermáticas foram recuperadas dos três segmentos epididimários (Cabeça, corpo e cauda) e submetidas às avaliações de cinética espermática (CASA) e testes morfofuncionais. Foram avaliadas as atividades das enzimas antioxidantes SOD e GPx e mensurados os níveis de ATP em cada amostra epididimária. Espermatozoides recuperados da cauda do epidídimo apresentaram maior porcentagem de células móveis e progressivas e elevados níveis de ATP em comparação aos demais grupos. As células provenientes do corpo apresentaram maior susceptibilidade à peroxidação lipídica e membranas plasmática e acrossomal lesionadas. Foi nesse segmento que também observamos a migração da gota e o início da aquisição da motilidade, e correlação negativa entre gota distal e susceptibilidade à peroxidação. Em amostras da cabeça, houve correlação positiva entre produção de EROs e níveis de ATP, e alto PMM; e correlação negativa entre atividade da SOD e susceptibilidade à peroxidação lipídica em amostras da cabeça. Não foram observadas diferenças significativas em relação ao potencial de membrana mitocondrial (PMM) e a atividade da SOD e da GPx entre os diferentes segmentos. Por meio dos principais resultados, pudemos sugerir que as células presentes na cauda do epidídimo apresentam o aparato energético ativo, devido à alta porcentagem de células móveis e níveis de ATP. As amostras provenientes do corpo evidenciam que é neste segmento em que a motilidade se inicia e que ocorre os principais remodelamentos de membrana. As correlações observadas nos permitem inferir que as mitocôndrias de espermatozoides bovinos imaturos já estivessem ativas desde o início da maturação, produzindo energia e EROs. Além disso, a correlação nos mostra o papel protetor da SOD contra à peroxidação lipídica. Paralelamente, sugerimos que a gota participe firmemente da ativação da motilidade e desempenhe papel antioxidante contra as EROs. Assim, concluímos que as modificações celulares inerentes ao processo de maturação e a presença da gota citoplasmática sejam cruciais no status oxidativo e metabólico de espermatozoides bovinos imaturos, afim desenvolver a capacidade fecundante do espermatozoide. / Spermatogenesis is an orchestrated and coordinated process by which sperm are produced. In the end of this process, the excess cytoplasm present in the spermatids is phagocytosed, remaining a called cytoplasmic droplet. Spermatozoa in the stage of maturation present cytoplasmic droplet, which migrates from the proximal region to more distal regions in sperm cell. Studies relate the cytoplasmic remnant to the antioxidant protection and to metabolic activation of immature sperma. The physiological mechanisms of maturation and the oxidative and metabolic status of bovine epididymal cells are poorly elucidated. Thus, two experiments aimed to characterize the oxidative and metabolic status of bovine sperm during epididymal maturation, and the possible cytoplasmic droplet roles involved in this process. For this, sperm samples were recovered from the three epididymal segments (Caput, corpus and cauda) and submitted to spermatic kinetics analysis (CASA) and morphofunctional tests. The activities of the antioxidant enzymes SOD and GPx were evaluated and the levels of ATP in each epididymal sample. Sperm cells recovered from the cauda of the epididymis showed a higher percentage of motile and progressive cells and high levels of ATP compared to the other groups. Cells from the corpus showed elevated susceptibility to lipid peroxidation and lesioned plasma and acrosomal membranes. It was in this segment that we also observed the migration of cytoplasmic droplet and the beginning of the acquisition of motility, and negative correlation between distal droplet and susceptibility to peroxidation. In samples from the caput, there was a positive correlation between ROS production and ATP levels, and high PMM; and negative correlation between SOD activity and susceptibility to lipid peroxidation in caput samples. No significant differences were observed in relation to mitochondrial membrane potential (PMM) and SOD and GPx activity among the different segments.By means of the main results, we could suggest that cells present in the cauda of the epididymis present the active energy apparatus, due to the high percentage of mobile cells. Samples from the corpus show that is in this segment that the motility begins and the main membrane remodeling occurs. The observed correlations allow us to infer that mitochondria of immature bovine sperm are already active since the beginning of maturation, producing energy and ROS. In addition, the correlation shows us the protective role of SOD against lipid peroxidation. In parallel, we suggest that cytoplasmic droplet participates firmly in the activation of motility and plays an antioxidant role against ROS. Thus, we conclude that the cellular modifications inherent in the sperm maturation process and the presence of cytoplasmic droplet are crucial in the oxidative and metabolic status of immature bovine spermatozoa, in order to develop fecundant capacity.

[ES] Cualquier mejora en el conocimiento de la nutrición y el manejo de los futuros conejos reproductores debe considerarse como prioritario en la producción cunícola. Sin embargo, los principales esfuerzos en investigación se han centrado en estos animales durante la fase de reproducción propiamente dicha. La hipótesis inicial de esta tesis fue que alcanzar un desarrollo temprano adecuado durante la gestación, lactancia, engorde y recría, con la ayuda de programas ajustados de alimentación en algunos de estos períodos, mejoraría el rendimiento reproductivo y la vida útil de los futuros conejos reproductores. Para evaluar esta hipótesis, se llevaron a cabo dos tipos de ensayos, tanto en conejos hembra de líneas maternas como en machos de líneas seleccionadas por velocidad de crecimiento y destinadas a la inseminación artificial. El primero de estos ensayos se centró en los diferentes patrones de crecimiento, desde el nacimiento hasta el final de la fase de recría, y su influencia en la carrera reproductiva y la vida útil del conejo. En el segundo tipo de pruebas, se evaluó el efecto del uso de diferentes dietas o programas de alimentación durante el período de recría en la productividad a corto y medio plazo. Los resultados muestran dos fases importantes en el desarrollo temprano, de acuerdo con sus efectos sobre el rendimiento reproductivo y la vida útil. Mostrar un mayor desarrollo corporal desde el nacimiento hasta los 63 días de vida parece tener una influencia positiva en el grado de madurez y la productividad al comienzo de su vida reproductiva, además de poder mejorar su supervivencia a corto plazo, pero con posibles efectos negativos en la esperanza de vida a largo plazo. Sin embargo, el desarrollo durante el período de recría (desde los 63 días de vida hasta el comienzo de la carrera reproductiva) parece tener un mayor impacto en la productividad y la esperanza de vida de nuestros futuros conejos reproductores. Las hembras más engrasadas en la primera inseminación tuvieron tamaños de camada más pequeños y un mayor riesgo de ser sacrificadas que las magras (P<0.05). Además, los machos que mostraron una mayor ganancia media diaria durante el período de recría tuvieron un número y porcentaje de eyaculados viables más bajos a lo largo de su vida productiva y mayor riesgo de muerte o sacrificio. Estos resultados podrían indicar que la clave para llevar a cabo un desarrollo adecuado durante el período de recría debería basarse tanto en conseguir que los conejos alcancen un grado de madurez apropiado, tanto fisiológica como reproductivamente, así como evitar un excesivo engrasamiento al inicio de su vida productiva. En los ensayos destinados a evaluar los programas de alimentación durante la recría, el uso de una restricción alimentaria en hembras, y especialmente el uso de dietas fibrosas (de 8.5 a 10 MJ ED/kg MS) permiten un desarrollo corporal gradual y adecuado a la edad de cubrición, con suficientes reservas corporales para afrontar el comienzo de la vida reproductiva y mejorando tanto su rendimiento reproductivo como su vida útil. El éxito de estos programas de alimentación de recría depende del momento y la duración de la aplicación de estos, mejorándose con la aplicación de un cambio a un pienso enriquecido energéticamente alrededor del primer apareamiento. En los machos, se observó que un programa de alimentación durante la recría adecuado debería adaptarse a la capacidad de ingesta de estos y a sus necesidades nutricionales en períodos concretos de la recría, consiguiendo así mejoras en algunos parámetros del semen al inicio de su vida reproductiva. En conclusión, tanto un desarrollo temprano adecuado desde la gestación hasta el comienzo de su vida reproductiva, como el uso de programas adecuados de alimentación durante la recría podrían mejorar significativamente el rendimiento reproductivo futuro, así como la esperanza de vida, tanto en conejos he / [CAT] Qualsevol millora en el coneixement tant de la nutrició com del maneig dels futurs conills de criança ha de considerar-se com a prioritari en la producció de conills. No obstant açò, els principals esforços en investigació s'han centrat en aquests animals durant la fase de reproducció pròpiament dita. La hipòtesi inicial d'aquesta tesi va ser que aconseguir un desenvolupament primerenc adequat durant la gestació, lactància, engreix i criança, amb l'ajuda de programes ajustats d'alimentació en alguns d'aquests períodes, milloraria el rendiment reproductiu i la vida útil dels futurs conills reproductors. Per a avaluar aquesta hipòtesi, es van dur a terme dos tipus d'assajos, tant en conills femella de línies maternes, com en mascles de línies seleccionades per a la velocitat de creixement i destinades a la inseminació artificial. El primer d'aquests assajos es va centrar en els diferents patrons de creixement, des del naixement fins al final de la fase de criança, i la seua influència en la carrera reproductiva i la vida útil del conill. En el segon tipus de proves, es va avaluar l'efecte de l'ús de diferents dietes o programes d'alimentació durant el període de criança, en la productivitat a curt i mig termini. Els resultats obtinguts semblen indicar que podríem diferenciar dues fases en el desenvolupament primerenc, d'acord amb els seus efectes sobre el rendiment reproductiu i la vida útil. Mostrar un major desenvolupament corporal des del naixement fins als 63 dies de vida sembla tenir una influència positiva en el grau de maduresa i la productivitat al començament de la seua vida reproductiva, a més de poder millorar la seua supervivència a curt termini, però amb possibles efectes negatius en l'esperança de vida a llarg termini. No obstant açò, el desenvolupament durant el període de sembla tenir un major impacte en la productivitat i l'esperança de vida dels nostres futurs conills reproductors. Les femelles més greixades en la primera inseminació van tenir grandàries de ventrada més xicotets (tant nascuts com deslletats) i un major risc de ser sacrificades que les magres (P<0.05). A més, els mascles que van mostrar un major guany mitjà diari durant el període de criança van tenir un nombre i percentatge d'ejaculats viables més baixos al llarg de la seua vida productiva i major risc de mort o sacrifici. Aquests resultats podrien indicar que la clau per a dur a terme un desenvolupament adequat durant el període de criança hauria de basar-se tant a aconseguir que els conills aconseguisquen un grau de maduresa apropiat, per a afrontar els futurs desafiaments productius, com evitar un excessiu greixatge a l'inici de la seua vida productiva. En els assajos destinats a avaluar els programes d'alimentació durant la criança, l'ús d'una restricció alimentària en femelles, i especialment l'ús de dietes fibroses (de 8.5 a 10 MJ ED/kg MS) permeten un desenvolupament corporal gradual i adequat a l'edat de cobriment, amb suficients reserves corporals per a afrontar el començament de la vida reproductiva i millorant tant el seu rendiment reproductiu com la seua vida útil. L'èxit d'aquests programes d'alimentació de criança depèn del moment i la durada de l'aplicació d'aquests, millorant-se amb l'aplicació d'un canvi a un pinso enriquit energèticament al voltant del primer cobriment. En els mascles, es va observar que un programa d'alimentació durant la criança adequat hauria d'adaptar-se a la capacitat d'ingesta d'aquests i a les seues necessitats nutricionals en períodes concrets de la criança, aconseguint així millores en alguns paràmetres del semen a l'inici de la seua vida reproductiva. En conclusió, tant un desenvolupament primerenc adequat des de la gestació fins al començament de la seua vida reproductiva, com l'ús de programes adequats d'alimentació durant la criança podrien millorar significativament el rendiment reproductiu futur, així com l'esperança / [EN] Any improvement on the knowledge of both nutrition and management of the future rabbit breeders should be considered as crucial. However, main research efforts have been focused on animals during reproduction phase. The initial hypothesis of this thesis was that achieving an adequate early development during young rabbits' gestation, lactation, fattening and rearing, with the help of fitted feeding programmes in some of these periods, would be improved reproductive performance and lifespan of the future breeding rabbits. To evaluate this hypothesis, two types of trials, both in rabbit females from maternal lines selected for litter size at weaning and males from paternal lines selected for growth rate and intended on artificial insemination, were carried out. The first of these trials were mainly focused on the different growth patterns, from birth to the end of the rearing age, and their influence on rabbit's reproductive career and lifespan. In a second type of trials, the effect of the use of different diets or feeding programs during the rearing period in the performance in the short- medium-term was evaluated. The results obtained from the evaluation of the different growth patterns trials seem to indicate that, we could differentiate two parts on the early development according to their effects on reproductive performance and lifespan. To show a greater body development from birth to 63 days of life seems to have a positive influence on the maturity degree and productivity at the beginning of their reproductive life, as well as being able to improve their survival in the short-term, but it could be even negative for long-term lifespan. However, the development during the rearing period (from 63 days of life to the beginning of reproduction career) seems to have a higher impact on the productivity and lifespan of our rabbit breeders. Fatter rabbit females at first insemination had smaller litter sizes (born and weaned) and a higher risk of being culled (+13% per positive change in mm of perirenal fat) than lean ones (P<0.05). Also, rabbit males that showed a greater average daily gain during rearing period had a lower number and percentage of profitable ejaculates through it productive life (-10.1 and -4.9% per each 10 g of daily gain increase, respectively; P<0.05) and higher risk of death or culling (+16.2% per each increase in one standard deviation unit on live weight; P<0.05). These results could indicate that the key to carrying out an adequate development during the rearing period should allow the rabbits to reach an appropriate degree of physiological and reproductive maturity to face the future productive challenges, avoiding an excessive fatness at the beginning of their productive life. The use of a feeding restriction in rabbit females, and especially the use of fibrous diets (from 8.5 to 10 MJ DE/ kg DM) lead a gradual and adequate body development at mating, with enough body reserves to face the beginning of reproduction life and improving their whole reproductive performance and lifespan. The success of these rearing feeding programs depends in the moment and duration of application of them and improved with the application of a nutritional flushing around first mating. In rabbit males, it was observed that an adequate rearing feeding program should adapt it to the male's intake capacity and their nutritional requirements rearing period, especially to their high DP needs at the beginning of rearing period or when their requirements were close to maintenance, to improve some semen parameters at the beginning of their reproduction life. In conclusion, both the adequate early development of future rabbit breeders, from their own gestation to the beginning of their reproductive life, and the use of appropriate rearing feeding programs could significantly improve their future reproductive performance, as well as their life expectancy, both in rabbit females and males. / Martínez Paredes, EM. (2019). Rearing programmes for breeding rabbits. Effect of early development and feeding on future reproductive performance of rabbit females and males [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/124969 / TESIS

L’hypoxie désigne une baisse de la biodisponibilité en oxygène au niveau tissulaire. La combinaison de l’hypoxie intermittente et de l’hypercapnie est identifiée dans le cadre de plusieurs maladies respiratoires comme un élément physiopathologique déterminant. Cependant, des travaux de recherche suggèrent qu’une exposition à l’hypoxie hypo- ou normocapnique à l’éveil peut améliorer la santé cardiovasculaire. La combinaison d’une exposition hypoxique et de l’entraînement à l’effort est utilisée par les athlètes pour améliorer la performance sportive aérobie. Des études pilotes récentes y compris chez le malade chronique indiquent que l’exposition à l’hypoxie modérée au repos ou à l’effort chez le patient est susceptible d’induire des gains significatifs en termes de santé cardiovasculaire, de composition corporelle et de statut métabolique.Nous nous sommes intéressés aux effets cardiorespiratoires et tissulaires de l’exposition hypoxique normobarique chez le sujet sain et chez la personne en surpoids ou obèse présentant un risque ou des anomalies cardio-métaboliques. Nous avons étudié l’efficacité de 2 types de conditionnement au repos consistant en une hypoxie continue ou une hypoxie intermittente et un entraînement à l’effort hypoxique par comparaison à la situation normoxique. Nous avons tout d’abord étudié les effets d’une exposition hypoxique à court terme au repos chez 14 sujets sains. Nous avons ensuite étudié les effets cardiorespiratoires, tissulaires, vasculaires et métaboliques d’un programme de conditionnement hypoxique normobarique à moyen terme au repos chez 35 patients en surpoids ou obèse. Nous avons de plus réalisé chez 24 sujets sains une étude préliminaire afin de vérifier la faisabilité et de caractériser les réponses cardio-respiratoires et l’oxygénation tissulaire au cours d’un exercice aigu à charge constante d’intensité modérée ou intermittent intense en hypoxie comparé à une condition placébo normoxique. La dernière étude a consisté à étudier les conséquences cardiorespiratoires, tissulaires, vasculaires et métaboliques d’un programme d’entraînement à l’effort en hypoxie par rapport au même programme en normoxie chez 23 patients en surpoids ou obèses.L’étude réalisée chez le sujet sain met en évidence l’intérêt à court terme d’un conditionnement hypoxique intermittent au repos sur des variables associées aux risques cardiovasculaires (diminution de la pression artérielle systolique en normoxie et augmentation de la variabilité sinusale) et une modulation de l’hypoxie tissulaire. Nous avons montré chez le sujet sain que l’hypoxie combiné à l’exercice aigu provoque une diminution de l’oxygénation musculaire similaire mais une diminution de l’oxygénation du cortex préfrontal plus importante par comparaison à un effort normoxique à même intensité relative. Ensuite, chez le sujet en surpoids ou obèse, nous avons montré que le conditionnement hypoxique passif chronique induit une diminution de la pression artérielle diastolique de repos en normoxie, une augmentation de la réponse ventilatoire hypoxique et une diminution de la variabilité cardiaque (après conditionnement par hypoxie intermittente seulement) et que le conditionnement hypoxique actif chronique améliore l’aptitude maximale aérobie par rapport à une situation placébo normoxique.Les résultats obtenus montrent la faisabilité de plusieurs conditionnements hypoxiques prometteurs au plan vasculaire y compris chez le sujet en surpoids ou obèse limité à l’exercice musculaire. Le conditionnement hypoxique actif montre également des bénéfices accrus sur l’aptitude aérobie. Ces protocoles de conditionnement doivent être affinés en vue d’optimiser leur efficacité en termes de perte de poids et d’amélioration du risque cardio-vasculaire et métabolique dans des populations présentant une obésité associée à une morbidité cardio-métabolique. Ils représentent également une piste thérapeutique innovante dans d’autres pathologies chroniques / Hypoxia refers to a decrease in the oxygen bioavailability at the tissue level. The combination of intermittent hypoxia and hypercapnia is identified in several respiratory diseases as a critical pathophysiological element. However, research suggests that exposure to hypo- or normocapnic hypoxia can improve cardiovascular health. The combination of hypoxic exposure and exercise training has been used by athletes to improve aerobic exercise performance. Recent pilot studies in patients with chronic diseases indicate that exposure to moderate hypoxia at rest or during exercise is likely to induce significant gains in cardiovascular health, body composition and metabolic status.We investigated the effects of normobaric hypoxic exposure on cardiorespiratory and tissue function in healthy subjects, overweight or obese subjects at risk or with cardio-metabolic abnormalities. We assessed the efficacy of 2 types of passive hypoxic conditioning consisting in sustained hypoxia or intermittent hypoxia and hypoxic exercise training in comparison with normoxic condition. First, we assessed the effects of short-term hypoxic exposure at rest in 14 healthy subjects. Then, we evaluated the cardiovascular and metabolic effects of a 8-week normobaric hypoxic conditioning program at rest (intermittent or sustained hypoxia) in 35 overweight or obese patients, compared to placebo normoxic exposure. Next, we conducted a preliminary study in 24 healthy subjects to assess the acute responses to submaximal constant-load and high intensity interval cycling exercise performed in normoxia and in hypoxia. The last study aimed to compare the effect of an 8-week exercise training program performed either in normoxia or hypoxia on maximal aerobic capacity in overweight or obese subjects.In the healthy subject, we emphasized the rapid benefits of intermittent hypoxic conditioning on cardiovascular function (lower baseline systolic blood pressure and increased heart rate variability) and the modulation of tissue deoxygenation in response to hypoxia. We have also shown in healthy subjects that acute exercise (combined with hypoxia causes a similar decrease in muscle oxygenation but a greater prefrontal cortex deoxygenation compared to normoxic condition. Then, in the overweight or obese subject, we have shown that chronic passive hypoxic conditioning induces a decrease in diastolic blood pressure at rest in normoxia, an increase in the hypoxic ventilatory response and a decrease in heart rate variability after intermittent hypoxic conditioning only. In addition, chronic active (exercise training) hypoxic conditioning improves the maximal aerobic capacity compared to placebo normoxic training.Our results show the feasibility of several hypoxic conditioning strategies and their interesting effects on the vascular function in overweight/obese subjects presenting exercise limitations impeding exercise reconditioning. In addition, active hypoxic conditioning showed a greater effect on physical fitness than normoxic exercise training. These hypoxic conditioning strategies must be further optimized to improve their efficacy regarding weight loss and cardiometabolic morbidity in obese. They also represent promising therapeutic opportunities for other chronic diseases

This thesis investigates the complexity of the obesity phenotype by characterizing the inflammatory status of Metabolically Healthy Obese (MHO) individuals. More specifically, this work has examined circulating inflammatory markers in MHO individuals and compared it to Lean Healthy (LH) and Metabolically Abnormal Obese (MAO) subjects. Thirty participants (n=10/group) were recruited as part of the Diabetes Risk Assessment (DRA) study, and classified according to adiposity and metabolic status. Despite a similar level of adiposity compared to MAO individuals, MHO subjects presented a more favourable inflammatory profile. Specifically, MHO individuals had levels of hsCRP and IL-6 comparable to LH subjects and lower than MAO subjects. Also, MHO subjects presented similar levels of high molecular weight adiponectin as the MAO group, but PDGF-ββ levels were intermediate to those of the LH and MAO groups. Overall, the distinct inflammatory profile observed in MHO subjects demonstrates the unique status of these individuals, reinforcing that obesity is a complex and heterogeneous phenotype. / Public Health Agency of Canada, Ontario Graduate Scholarships, Queen Elizabeth II Graduate Scholarships in Science and Technology, Canada Foundation for Innovation