High-intensity interval training (HIIT) consists of short intervals of exercise at high intensity intermitted by intervals of lower intensity and is associated with improvement of body composition and metabolic health in adults. Studies in overweight adolescents are scarce. We conducted a randomized controlled trial in overweight adolescents to compare acceptance and attendance of HIIT with or without weekly motivational encouragement through text messages and access to a study website. HIIT was offered for six months (including summer vacation) twice a week (60 min/session). Participation rates were continuously assessed and acceptance was measured. Clinical parameters were assessed at baseline and after six months. Twenty-eight adolescents participated in this study (age 15.5 +/- 1.4; 54% female). The standard deviation score for body mass index over all participants was 2.33 at baseline and decreased by 0.026 (95% CI - 0.048 to 0.10) units, p = 0.49. Waist to height ratio was 0.596 at baseline and decreased by 0.013 (95% CI 0.0025 to 0.024), p = 0.023. Participation within the first two months ranged from 65% to 75%, but fell to 15% within the last three months. Attendance in the intervention group was 14% (95% CI - 8 to 37), p = 0.18, higher than the control group. Overall program content was rated as \"good\" by participants, although high drop-out rates were observed. Summer months constitute a serious problem regarding attendance. The use of media support has to be assessed further in appropriately powered trials.

Physical activity results in various types of stress in skeletal muscle including energetic, oxidative, and heat stress. Acute exposure to stress impairs skeletal muscle mitochondrial function. In contrast, chronic intermittent exposure to mild stress through exercise training results in increased mitochondrial content and respiratory capacity. While oxidative and energetic stress have received much attention regarding their long-term effect on skeletal muscle mitochondria, heat stress is not well understood. The purpose of this work was to investigate the effects of localized heat therapy on human skeletal muscle mitochondria, and to compare these effects to those of high-intensity interval exercise training. To accomplish this purpose, 35 subjects were assigned to receive 6 weeks of sham therapy, heat therapy, or exercise training; all localized to the quadriceps muscles of the right leg. Two-hour sessions of short-wave diathermy were used for the heat therapy, and identical sessions were used for sham therapy, but the diathermy units were not activated. Forty-minute sessions of single-leg extension, high-intensity interval training were used for the exercise intervention. All interventions took place three times per week. Muscle biopsies were performed at baseline, and after three and six weeks of intervention. Muscle fiber bundles were isolated and permeabilized for measurement of oxygen consumption via high-resolution respirometry. The primary finding of this work was that heat therapy improves mitochondrial respiratory capacity by 24.8 ± 6.2% compared to a 27.9 ± 8.7% improvement following exercise training. Both heat and exercise significantly increased mitochondrial respiration compared to baseline measures (p<0.05). Fatty acid oxidation and citrate synthase activity were also increased following exercise training by 29.5 ± 6.8% and 19.0 ± 7.4%, respectively (p<0.05). However, contrary to our hypothesis, heat therapy did not increase fatty acid oxidation or citrate synthase activity. Neither heat nor exercise training increased mitochondrial respiratory protein content. Overall these results suggest that heat therapy significantly improves mitochondrial function, but not to the same degree as exercise training.

The obesity epidemic is an important global health concern. Obesity is associated with a number of diseases including type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), cardiovascular disease, and some cancers. Insulin resistance, a precursor to type 2 diabetes, is defined as an unresponsiveness of metabolic tissues to insulin, leading to long-term hyperglycemia and hyperinsulinemia. The fatty acid-induced model of insulin resistance indicates that an accumulation of lipid intermediates interferes with insulin signal transduction leading to insulin resistance. It is, therefore, important to examine means by which these lipid intermediates can be reduced to alleviate interferences in insulin signaling in the treatment of insulin resistance and type 2 diabetes. Exercise and metformin are two common interventions in patients with type 2 diabetes and obesity. They both commonly activate AMP-activated protein kinase (AMPK). AMPK contributes to a number of metabolic processes including increased glucose and fatty acid oxidation. However, the effects of AMPK activation on insulin sensitivity are currently not fully understood. This compilation of studies examined the insulin sensitizing effects of AMPK activation via metformin, exercise, and novel AMPK activator R419 in obese mice. In Chapter 2 we show that metformin increases AMPK phosphorylation of acetyl-CoA carboxylase (ACC) 1 Ser79 and ACC2 Ser212, resulting in increased fatty acid oxidation, decreased lipid content and improvements in hepatic insulin sensitivity. In Chapter 3 we show that exercise-induced improvements in insulin sensitivity occur independent of AMPK phosphorylation of ACC phosphorylation sites and independent of lipid content in the liver. Finally, in Chapter 4 we show that R419 improves skeletal muscle insulin sensitivity independent of AMPK and lipid content but improves exercise capacity via a skeletal muscle AMPK-dependent pathway in obese mice. These findings suggest that future studies examining the effects of AMPK activation in obesity will aid in our understanding of the mechanisms of insulin resistance and introduce methods of prevention and treatment of obesity and type 2 diabetes. / Thesis / Doctor of Philosophy (PhD)

Objectif. L’activité physique a des bénéfices sur la santé mentale des personnes vivant avec des troubles psychotiques. L’effort aérobie de type continue étant l’intervention la plus populaire dans la littérature, certaines études ont également étudié le type d’effort de haute intensité par intervalles, mais n’ont pas observé ses effets à long terme. La présente étude vise premièrement à observer le maintien des bénéfices auprès de personnes ayant des troubles psychotiques, après une intervention de six mois de haute intensité par intervalles. Deuxièmement, elle vise à déterminer les prédicteurs de participation à la pratique d’activité physique. Méthodes. Soixante-six sujets (37.9% de femmes, 30.73 ± 7.23 ans) diagnostiqués avec un trouble psychotique selon le DSM-5 ont participé à une intervention supervisée de haute intensité par intervalles de course sur tapis, durant six mois, à raison de deux séances de 30 minutes par semaine. Après cette intervention, il a été offert aux sujets un accès gratuit aux installations ou se sont déroulées les séances pendant à nouveau six mois, sans supervision. Les sujets ont été évalués avant et après l’intervention, puis six mois après l’arrêt de la supervision, soit 12 mois après le premier temps de mesure. La symptomatologie (PANSS), le fonctionnement global (GAF) et social (SOFAS) ont été évalués. Les scores des questionnaires mentionnés ci-dessus ont été analysées statistiquement par des modèles mixtes linéaires et des ANOVA à une voie. Résultats. Les résultats ont montré un maintien de l’impact positif de l’intervention sur les symptômes négatifs (p = 0,004) et globaux (p = 0,01). Les facteurs prédicteurs de la participation aux séances d’activité physique ont montré que les individus ayant participé à moins de 64% des séances sont ceux ayant un moins bon fonctionnement global (GAF : p = 0,02) et social (SOFAS : p ˂ 0,001) et des symptômes plus sévères (PANSS : négatifs : p = 0,02 ; positifs : p = 0,01 ; globaux : p = 0,04). Conclusion. Le maintien des bénéfices n’a été observé qu’au niveau des symptômes négatifs, ce qui implique des stratégies supplémentaires dans l’élaboration de l’intervention et ses modalités. De plus, nos analyses prédictives révèlent qu'une amélioration du fonctionnement social et global, ainsi qu'une réduction de la sévérité des symptômes, sont associées à une participation accrue à l'activité physique chez nos participants. / Aims. Physical activity has mental health benefits for people with psychotic disorders. Continuous aerobic exercise being the most popular intervention in the literature, some studies have also investigated high-intensity interval training but have not investigated its long-term effects. This study had two aims. First, to observe whether the benefits of a six-month high intensity interval training intervention could be maintained among people with psychotic disorders. Second, to determine the predictors of participation in physical activity participation. Methods. Sixty-six subjects (37.9% women, 30.73 ± 7.23 years old) diagnosed with psychotic disorder according to DSM-5 participated in a supervised six-month high-intensity interval treadmill running intervention : twice per week, 30 minutes per session. After the intervention, subjects were offered free access to the facilities where the sessions were held for another six months without supervision. The subjects were evaluated before and after the intervention, and six months after the end of supervision, which was 12 months after the first measurement. Symptomatology (PANSS), global (GAF) and social (SOFAS) functioning were evaluated. The scores of the above-mentioned questionnaires were statistically analyzed using linear mixed models and one-way ANOVA. Results. The results showed a maintenance of the positive impact of the intervention on negative (p = 0.004) and global (p = 0.01) symptoms only. Predictors of participation in physical activity sessions showed that individuals who participated in less than 64% of the sessions had poorer global functioning (GAF: p = 0.02) and social functioning (SOFAS : p ˂ 0,001) and more severe symptoms (PANSS: negative: p = 0.02; positive: p = 0.01; global: p = 0.04). Conclusion. The maintenance of benefits was only observed in terms of negative symptoms, which implies the need for additional strategies in the development and implementation of the intervention. In addition, the prediction analyses of participation in physical activity demonstrated that individuals with better global and social functioning and less severe symptoms are more likely to practice physical activity.

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Introduktion: Fysisk aktivitet har stor betydelse för en god hälsa när vi åldras. Trots det är en stor andel av äldre personer stillasittande. Brist på tid och obehagliga upplevelser ses som hinder till träning. Högintensiv träning kan utföras på kort tid och kan ge större hälsofördelar än medelintensiv träning. Däremot har högintensiv träning upplevts för ansträngande och olämpligt för en stillasittande population. En negativ affektiv respons kan minska följsamheten i träningen vilket belyser vikten av att anpassa högintensiv träning för äldre. Forskning om upplevelser av en anpassad högintensiv träningsregim saknas i dagsläget. Syfte: Att beskriva upplevelser av supramaximala cykelintervaller, träningsmotivation och fortsatta träningsvanor hos informanterna, sex månader efter genomförd intervention.  Metod: I studien användes en kvalitativ induktiv ansats. Sex månader efter en träningsintervention genomfördes semi-strukturerade intervjuer. Tio av de intervjuerna har analyserats i denna studie, med deltagare som hade genomfört anpassade supramaximala intervaller på cykel två gånger per vecka under tolv veckor. Materialet analyserades med kvalitativ innehållsanalys. Resultat: Analysen av intervjuerna resulterade i fem kategorier: Träningen fyllde en viktig plats i livet, Att uppleva kroppen genom träning, Gemenskap som ger drivkraft, Träningen som stärkande upplevelse, och Att förändra eller falla in i gamla vanor. Konklusion: Supramaximala anpassade intervaller i grupp är en träningsform som verkar passa äldre personer. Träningen har upplevts lättsam och tidseffektiv. Gruppen har varit viktig och bidragit med glädje och motivation i träningen. Trots ökad motivation till träning har många fallit tillbaka i gamla vanor efter träningsperioden. Individuellt motstånd möjliggör träning på rätt intensitet i en grupp med blandad träningsvana. Dessa insikter kan komma att bli viktiga för att implementera träningsformen.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

O diabetes mellitus tipo 1 (DM1) está associado com condições pró-oxidantes, próinflamatórias e elevado risco cardiovascular, enquanto o exercício físico pode ser considerado um dos melhores instrumentos não farmacológicas para o tratamento do DM1. Nesse contexto, exercícios que propiciem um menor risco hipoglicêmico e diversos benefícios sobre a saúde devem ser estimulados. Um dos objetivos da tese foi verificar a influência da realização de exercícios de força (SE) antes ou depois do exercício intervalado de alta intensidade (HIIE) sobre o comportamento glicêmico durante e logo após uma sessão de esforço (estudo transversal) (manuscrito original 1). Entretanto, o principal objetivo desta tese foi comparar os efeitos do treinamento intervalado de alta intensidade (HIIT), do treinamento de força (ST) e da combinação destes (ST+HIIT), sobre marcadores sanguíneos inflamatórios, de estresse oxidativo (OS) e metabolismo glicêmico em pacientes com DM1 através de um ensaio clínico randomizado (ECR) (manuscrito original 2). Com relação ao estudo transversal (manuscrito 1), em três visitas, adultos fisicamente ativos realizaram 30 min de SE antes de 30 min de HIIE ou realizaram a ordem inversa da sessão (HIIE+SE) ou permaneceram em repouso nesse período (REST). A glicemia capilar foi mensurada a cada 15 min durante e até 60 min da recuperação. Comparando-se com os valores basais, a condição HIIE+SE reduziu a glicemia em 30, 45 e 60 min, enquanto SE+HIIE adiou esta queda glicêmica para a partir de 60 min. HIIE+SE também acarretou uma maior glicemia em 105 min quando comparado a 60 min. A quantidade ingerida de carboidratos durante as sessões, bem como a dose insulínica no mesmo dia antes e depois dos protocolos, além dos episódios noturnos de hipoglicemia, foram similares entre as três condições. Conclui-se que pacientes com DM1 propensos a desenvolver hipoglicemia associada ao exercício devem realizar SE antes do HIIE na mesma sessão. Com relação ao estudo principal (ECR) (manuscrito original 2), após 4 semanas de um período controle, pacientes fisicamente inativos com DM1 foram randomizados para realização de 10 semanas de HIIT, ST ou ST+HIIT, praticados 3x/sem. As sessões de HIIT duraram 25 min, as de ST 40 min, e as de ST+HIIT ~65 min. Os desfechos foram analisados através do modelo de equações de estimativas generalizadas (GEE), com post hoc de Bonferroni. ST, HIIT e ST+HIIT melhoraram parâmetros glicêmicos e antioxidantes, mas não os marcadores plasmáticos de inflamação e de OS. Interessantemente, as intervenções reduziram as concentrações de receptores solúveis para produtos finais da glicação avançada. Entretanto, o conteúdo intracelular das proteínas de choque térmico de 70 kDa aumentou somente depois do HIIT. Enquanto a dose diária de insulina utilizada reduziu apenas no grupo ST+HIIT, todos os protocolos induziram benefícios antropométricos, cardiorrespiratórios e funcionais. Sob uma perspectiva prática, conclui-se que um maior volume (ST+HIIT) de treinamento é necessário para o benefício adicional da redução insulínica diária. Já o HIIT, por exemplo, é diretamente aplicável para pessoas que reclamam da falta de tempo, podendo ser recomendado devido a vantagem extra com relação a proteínas anti-inflamatórios em células imunológicas. / Type 1 diabetes mellitus (DM1) is associated with prooxidant and proinflammatory conditions, besides an increased cardiovascular risk, while exercise may be considered one of the best nonpharmacological tools for DM1 treatment. In this context, exercises linked with a lower hypoglycemic risk and several health benefits should be stimulated. One of the goals of this thesis was to verify the influence of performing strength exercises (SE) before or after highintensity interval exercise (HIIE) on glycaemia during and postexercise (cross-sectional study) (original manuscript 1). However, the main objective of this thesis was to compare the effects of high-intensity interval training (HIIT), strength training (ST) or their combination (ST+HIIT), on blood inflammatory, oxidative stress (OS) and glycemic markers in DM1 patients using a randomized clinical trial (ECR) (original manuscript 2). Regarding the crosssectional study (original manuscript 1), in three visits, physically active adults performed 30 min of SE before 30 min of HIIE or performed the reverse order (HIIE+SE) or rested for 30 min (REST). Capillary glycaemia was measured each 15 min during and 60 min postexercise recovery. HIIE+SE lowered glycaemia at 30, 45 and 60 min compared with baseline concentrations, while SE+HIIE postponed this glucose decayment to 60 min and thereafter. HIIE+SE increased glycaemia at 105 min compared with 60 min. Carbohydrates ingested during exercise, insulin dosage at same day before and after protocols, and nocturnal hypoglycemia episodes were similar among the three conditions. DM1 patients prone to develop exercise-associated hypoglycemia should perform SE before HIIE in a single session. Regarding the main study (ECR) (original manuscript 2), after 4-week control period, physically inactive patients with DM1 were randomly assigned to 10-week HIIT, ST or ST+HIIT protocol, performed 3 x/week. HIIT sessions lasted 25 min, ST lasted 40 min and ST+HIIT sessions lasted ~65 min. Blood biochemical, anthropometric, strength and cardiorespiratory fitness variables were assessed. Outcomes were analyzed via generalized estimating equations (GEE), with Bonferroni post hoc analysis. ST, HIIT and ST+HIIT improved glycemic and antioxidant parameters, but not plasma inflammatory or OS markers. Noteworthy, interventions reduced soluble receptors for advanced glycation end products levels. However, intracellular heat shock protein 70 content increased only after HIIT. While daily insulin dosage decreased only in the ST+HIIT group, all training models induced anthropometric and functional benefits. From a practical clinical perspective, a higher volume (SE+HIIT) of training is required for the additional benefit of daily insulin reduction. The HIIT, for example, is directly applicable for people who claim lack of time, and it may be 13 recommended due to extra advantage concerning anti-inflammatory proteins at immunological cells.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal