In recent years there has been a surge in interest concerning high intensity intermittent exercise training (HIT) due to its ability to confer rapid notable cardio-metabolic health benefits. Specifically, HIT has been shown to improve insulin sensitivity and glycaemic control as well as other cardiovascular health factors after just 2 weeks of training (typically 6 training sessions). This thesis investigated the potential therapeutic role of HIT training within obese cohorts specifically addressing metabolic health, inclusive of inflammatory profiles and glycaemic control.

The IL-6 system is key in the development of chronic low-grade inflammation. It is known to be upregulated in response to acute exercise and lowered at rest after exercise training. IL-6 has both anti- and pro-inflammatory properties and moderation of this cytokine could alleviate chronic low-grade inflammation which is associated with obesity and Type 2 diabetes mellitus (T2DM). This thesis investigated the interplay between inflammation, glycaemic control and high intensity intermittent training (HIIT) - an exercise regimen that has been shown to yield many health benefits. There was a greater increase in IL-6 after an acute bout of HIIT than continuous moderate intensity exercise, where external work was matched (Chapter 4). Although sIL-6R and the IL-6/sIL-6R complex were both significantly increased after acute exercise there were no differences between HIIT and moderate intensity exercise. In response to 2 weeks HIIT there was a significant reduction in IL-6 and increase in IL-6R in adipose tissue in overweight and obese males (Chapter 5). It was also determined that IL-6R present in adipose tissue is at least partly composed of the membrane-bound IL-6R isoform (Chapter 6). Reductions in circulating sIL-6R, the IL-6/sIL-6R complex, MCP-1 and adiponectin, as well as a decrease in waist circumference and increase in peak oxygen uptake during exercise were also induced after 2 weeks HIIT (Chapter 5). Young adults with T2DM (< 40 y) displayed elevated levels of inflammatory proteins in comparison to lean controls, however there were no significant differences in comparison to obese controls (Chapter 7). In conclusion, the findings of this thesis demonstrate that acute and repeated bouts of HIIT have positive effects on the inflammatory profile in the circulation and adipose tissue, particularly in relation to the IL-6 system. It should be determined if HIIT is an achievable mode of exercise for patient populations, including T2DM patients, in order to downregulate the inflammatory profile.

INTRODUÇÃO: O modelo ideal de treinamento para promover melhores adaptações metabólicas e cardiopulmonares em crianças obesas permanece incerto. Em adultos, evidências sugerem que o exercício intermitente de alta intensidade e baixo volume seja uma estratégia eficiente na promoção dessas adaptações quando comparado ao exercício contínuo de grande volume e moderada intensidade. OBJETIVO: Comparar duas modalidades de treinamento físico (Treinamento Contínuo [TC] e Treinamento Intermitente de Alta Intensidade [TI]) nos parâmetros relacionados à saúde de crianças obesas entre 8 e 12 anos de idade. MÉTODOS: Trinta crianças obesas foram aleatoriamente alocadas em dois grupos: TC ou TI. O grupo TC realizou exercício contínuo com duração de 30 a 60 minutos a 80% da frequência cardíaca correspondente ao VO2 pico. O grupo TI realizou 3 a 6 sprints de 60 segundos de duração a 100% da velocidade pico atingida no teste, intercalados por 3 minutos de recuperação ativa a 50% da velocidade pico. A sessão do TI foi aproximadamente 70% mais curta do que a sessão do TC. Antes do iniciar o treinamento e após 12 semanas de intervenção, foram avaliados os parâmetros metabólicos, a composição corporal e a capacidade aeróbia dos voluntários. RESULTADOS: O VO2 absoluto (TC: 26,0%; TI: 19,0%) e o VO2 pico (TC: 13,1%; TI: 14,6%) foram significantemente maiores em ambos os grupos após a intervenção. Além disso, o tempo total de exercício (TC: 19,5%; TI: 16,4%) e a velocidade pico durante o teste cardiopulmonar (TC: 16,9%; TI: 13,4%) aumentaram significantemente com os treinamentos. Houve redução significante, em ambos os grupos, nos níveis de insulina (TC: 29,4%; TI: 30,5%) e no índice HOMA (TC: 42,8%; TI: 37,0%). A massa magra foi significantemente reduzida no grupo TI (2,6%), porém não foi observada a mesma redução no grupo TC (1,2%). Os dois grupos apresentaram uma redução significante do IMC após a intervenção (TC: 3,0%; TI: 5,0%). A análise de responsividade revelou um padrão similar de resposta para a maioria das variáveis em ambos os grupos, sendo as variáveis relacionadas à aptidão cardiovascular as mais responsivas. CONCLUSÃO: TI e TC foram igualmente eficazes na melhora dos parâmetros relacionados à saúde em crianças obesas. / INTRODUCTION: The optimal training model that elicits greater metabolic and cardiovascular adaptations in obese children remains unclear. In adults, there is evidence suggesting that low-volume sprint interval training (HIT) is a time-efficient strategy to induce metabolic adaptations that are comparable to high-volume traditional endurance training (ET). PURPOSE: To compare two modalities of exercise training (i.e., Endurance Training [ET] and High- Intensity Interval Training [HIT]) on health-related parameters in obese children aged between 8 and 12 years. METHODS: Thirty obese children were randomly allocated into either the ET or HIT group. The ET group performed a 30 to 60-minute continuous exercise at 80% of the peak heart rate (HR). The HIT group training performed 3 to 6 sets of 60-s sprint at 100% of the peak velocity interspersed by a 3-min active recovery period at 50% of the exercise velocity. HIT sessions last ~70% less than ET sessions. At baseline and after 12 weeks of intervention, aerobic fitness, body composition and metabolic parameters were assessed. RESULTS: Both the absolute (ET: 26.0%; HIT: 19.0%) and the relative VO2 peak (ET: 13.1%; HIT: 14.6%) were significantly increased in both groups after the intervention. Additionally, the total time of exercise (ET: 19.5%; HIT: 16.4%) and the peak velocity during the maximal graded cardiorespiratory test (ET: 16.9%; HIT: 13.4%) were significantly improved across interventions. Insulinemia (ET: 29.4%; HIT: 30.5%) and HOMA-index (ET: 42.8%; HIT: 37.0%) were significantly lower for both groups at POST when compared to PRE. Body mass was significantly reduced in the HIT (2.6%), but not in the ET group (1.2%). A significant reduction in BMI was observed for both groups after the intervention (ET: 3.0%; HIT: 5.0%). The responsiveness analysis revealed a very similar pattern of the most responsive variables among groups. CONCLUSION: HIT and ET were equally effective in improving important health related parameters in obese youth.

INTRODUÇÃO: O modelo ideal de treinamento para promover melhores adaptações metabólicas e cardiopulmonares em crianças obesas permanece incerto. Em adultos, evidências sugerem que o exercício intermitente de alta intensidade e baixo volume seja uma estratégia eficiente na promoção dessas adaptações quando comparado ao exercício contínuo de grande volume e moderada intensidade. OBJETIVO: Comparar duas modalidades de treinamento físico (Treinamento Contínuo [TC] e Treinamento Intermitente de Alta Intensidade [TI]) nos parâmetros relacionados à saúde de crianças obesas entre 8 e 12 anos de idade. MÉTODOS: Trinta crianças obesas foram aleatoriamente alocadas em dois grupos: TC ou TI. O grupo TC realizou exercício contínuo com duração de 30 a 60 minutos a 80% da frequência cardíaca correspondente ao VO2 pico. O grupo TI realizou 3 a 6 sprints de 60 segundos de duração a 100% da velocidade pico atingida no teste, intercalados por 3 minutos de recuperação ativa a 50% da velocidade pico. A sessão do TI foi aproximadamente 70% mais curta do que a sessão do TC. Antes do iniciar o treinamento e após 12 semanas de intervenção, foram avaliados os parâmetros metabólicos, a composição corporal e a capacidade aeróbia dos voluntários. RESULTADOS: O VO2 absoluto (TC: 26,0%; TI: 19,0%) e o VO2 pico (TC: 13,1%; TI: 14,6%) foram significantemente maiores em ambos os grupos após a intervenção. Além disso, o tempo total de exercício (TC: 19,5%; TI: 16,4%) e a velocidade pico durante o teste cardiopulmonar (TC: 16,9%; TI: 13,4%) aumentaram significantemente com os treinamentos. Houve redução significante, em ambos os grupos, nos níveis de insulina (TC: 29,4%; TI: 30,5%) e no índice HOMA (TC: 42,8%; TI: 37,0%). A massa magra foi significantemente reduzida no grupo TI (2,6%), porém não foi observada a mesma redução no grupo TC (1,2%). Os dois grupos apresentaram uma redução significante do IMC após a intervenção (TC: 3,0%; TI: 5,0%). A análise de responsividade revelou um padrão similar de resposta para a maioria das variáveis em ambos os grupos, sendo as variáveis relacionadas à aptidão cardiovascular as mais responsivas. CONCLUSÃO: TI e TC foram igualmente eficazes na melhora dos parâmetros relacionados à saúde em crianças obesas. / INTRODUCTION: The optimal training model that elicits greater metabolic and cardiovascular adaptations in obese children remains unclear. In adults, there is evidence suggesting that low-volume sprint interval training (HIT) is a time-efficient strategy to induce metabolic adaptations that are comparable to high-volume traditional endurance training (ET). PURPOSE: To compare two modalities of exercise training (i.e., Endurance Training [ET] and High- Intensity Interval Training [HIT]) on health-related parameters in obese children aged between 8 and 12 years. METHODS: Thirty obese children were randomly allocated into either the ET or HIT group. The ET group performed a 30 to 60-minute continuous exercise at 80% of the peak heart rate (HR). The HIT group training performed 3 to 6 sets of 60-s sprint at 100% of the peak velocity interspersed by a 3-min active recovery period at 50% of the exercise velocity. HIT sessions last ~70% less than ET sessions. At baseline and after 12 weeks of intervention, aerobic fitness, body composition and metabolic parameters were assessed. RESULTS: Both the absolute (ET: 26.0%; HIT: 19.0%) and the relative VO2 peak (ET: 13.1%; HIT: 14.6%) were significantly increased in both groups after the intervention. Additionally, the total time of exercise (ET: 19.5%; HIT: 16.4%) and the peak velocity during the maximal graded cardiorespiratory test (ET: 16.9%; HIT: 13.4%) were significantly improved across interventions. Insulinemia (ET: 29.4%; HIT: 30.5%) and HOMA-index (ET: 42.8%; HIT: 37.0%) were significantly lower for both groups at POST when compared to PRE. Body mass was significantly reduced in the HIT (2.6%), but not in the ET group (1.2%). A significant reduction in BMI was observed for both groups after the intervention (ET: 3.0%; HIT: 5.0%). The responsiveness analysis revealed a very similar pattern of the most responsive variables among groups. CONCLUSION: HIT and ET were equally effective in improving important health related parameters in obese youth.

L’optimisation de la performance en endurance oblige l’athlète à répéter des séances d’entraînement intermittent à haute intensité (EIHI), ce qui génère une fatigue neuromusculaire qui peut être préjudiciable. Ce type d’EIHI peut être aussi à l’origine des perturbations importantes de l’homéostasie générale affectant ainsi le volume plasmatique et les réponses physiologiques. Ainsi, l’objectif de ce travail de thèse est d’étudier l’effet de l’intensité d’EIHI (100% vs. 110% de VMA) sur les performances en endurances, marqueurs des dommages musculaires, le volume plasmatique et les réponses inflammatoires suite à l’exercice intermittent. Pour les études 2, 3 et 4, quatre groupes de sujets masculins et sains ont participé à ce travail. Ils ont été répartis d’une façon aléatoire en 2 groupes expérimentaux (GE100 et GE110) et en 2 groupes contrôles (GC100 et GC110). Pour l’étude 1, seulement 3 groupes (GE100, GE110 et GC) ont participé à l’expérimentation. En effet, deux programmes d’EIHI ont été mis à disposition avec un EI à 100% de VMA (pour GE100) et un EI à 110% de VMA (pour GE110). Les résultats montrent que l’EIHI s’accompagne d’une augmentation significative du volume plasmatique chez les deux groupes entrainés. Ces changements du volume plasmatique ont été accompagnés par une augmentation des performances physiques mesurée lors de l’exercice maximal à charge croissante et lors de l’exercice intermittent chez les groupes entrainés. Nos résultats ont révélé un taux d’amélioration plus élevé en suivant un EIHI à 110% de VMA. Des adaptations endocriniennes sont probablement à l’origine de ces modifications liées à l’entrainement intense. En effet, après entrainement, nous avons observé une diminution significative des marqueurs des dommages musculaires (au repos et à l’exercice intermittent) chez les sujets entrainés par rapport aux groupes contrôles. La différence liée à l’intensité de l’EIHI disparait après entrainement seulement entre les groupes entrainés. Le même constat a été observé concernant les concentrations plasmatiques des cytokines. En conclusion de ce travail de thèse, il semble que l’augmentation de l’intensité d’EIHI serait un bon moyen pour réduire et atténuer les effets délétères de l'EI supra-maximal. Le majeur fruit de ce travail est que l'intensité de 110% de VMA provoque une meilleur amélioration des performances aérobies que 100% de VMA, tout en avoir le même niveau de variation plasmatique, voir même des préférences au niveau des réponses inflammatoires. / Optimization of endurance performance requires the athlete to repeat high intensity interval training (HIIT). This type of training can induce a neuromuscular fatigue, a homeostasis perturbation which affects the plasma volume and the physiological responses. Thus, the aim of this study is to examine the effect of increasing HIIT intensity (100% vs. 110% of VMA) on endurance performance, muscular damage marker, plasma volume and inflammatory responses after an intermittent exercise (IE). For the first study, only 3 groups (EG100, EG110 and CG) participated in the experiment. However, in the2 sd, 3rd and 4th studies, 39 male volunteered to participate in this study. They were randomly assigned in control groups (CG100 and CG110), trained group with 100% of maximal aerobic velocity (MAV) (EG100) and trained group with 110% MAV (EG110). The training program consisted of 3 sessions a week during 8 weeks and presented only 30/30s IE. Before and after HIIT, participants performed a maximal graded test (MGT) and IE test at 100% or 110% MAV with 30s recovery at 50% MAV. Blood was collected at rest, at the end of the IE and after 15min of passive recovery. Results showed that increasing IT running intensity by 10% of MAV increases significantly the PVV at rest and after the IET. Despite the fact that EG100 and EG110 had the same PVV rise level after HIIT, greater aerobic performances were recorded in EG110. Our results revealed a higher improvement in response to HIIT at by following a 110% VAM EIHI. Endocrine adaptations are probably the cause of these changes related to intense training. Indeed, after training, we observed a significant decrease in markers of muscle damage (resting and intermittent exercise) in subjects trained compared to control groups. The difference related to the intensity of the EIHI disappears after training only between the groups trained. The same observation has been observed concerning the plasma concentrations of cytokines. In conclusion of this thesis work, it seems that increasing the intensity of EIHI would be a good way to reduce and mitigate the deleterious effects of the supra-maximal EI. In conclusion, HIIT at 110% MAV provoked better aerobic performances than 100% MAV, while having the same plasma volume and inflammatory responses levels.

Submitted by FLAVIANE POLETO DE OLIVEIRA null (fla_vb13@hotmail.com) on 2018-03-24T13:04:27Z No. of bitstreams: 1 Dissertação de mestrado_Flaviane Poleto_versão definitiva.pdf: 677650 bytes, checksum: b1dd23673956cadc620d339f8764038f (MD5) / Approved for entry into archive by Claudia Adriana Spindola null (claudia@fct.unesp.br) on 2018-03-26T12:39:15Z (GMT) No. of bitstreams: 1 oliveira_fp_me_prud.pdf: 677650 bytes, checksum: b1dd23673956cadc620d339f8764038f (MD5) / Made available in DSpace on 2018-03-26T12:39:15Z (GMT). No. of bitstreams: 1 oliveira_fp_me_prud.pdf: 677650 bytes, checksum: b1dd23673956cadc620d339f8764038f (MD5) Previous issue date: 2018-02-28 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O Treinamento Concorrente (a combinação de exercício aeróbio com treinamento de força) pode resultar em uma interferência negativa no desempenho de força. Além disso, há indicações de que a magnitude dessa interferência é dependente do modo/intensidade do exercício aeróbio. OBJETIVO: Sendo assim, o objetivo deste estudo foi comparar o efeito agudo do Treinamento de Força (TF) e do Treinamento Concorrente (TC) consistidos do Treinamento Intermitente de Alta Intensidade (HIIT) sob os ganhos de força máxima e volume durante 12 semanas. MÉTODOS: A amostra foi composta por 19 homens recreativamente ativos divididos entre o grupo TC (n=11) e grupo TF (n=8). O grupo TC realizou o HIIT (1min de corrida a 100% da velocidade aeróbia máxima intercalado por 1min de recuperação passiva até atingir 5 km) e em seguida uma sessão de treinamento de força constituída por oito exercícios com cargas de 8-12 repetições máximas, enquanto o grupo TF realizou apenas as sessões de treinamento de força. Ambos os grupos treinavam duas vezes por semana durante 12 semanas. A força máxima e o volume de treinamento durante uma sessão aguda foram avaliados pré, após oito e 12 semanas de treinamento. RESULTADOS: Um pequeno efeito de interferência foi observado na força máxima em relação à massa corporal após 12 semanas de treinamento com maiores melhorias no grupo TF quando comparado ao grupo TC. A mesma não foi observada após oito semanas de treinamento. CONCLUSÃO: Esses resultados sugerem que o volume realizado não exerceu impacto nos ganhos de força até oito semanas de treinamento concorrente constituído por HIIT. / The concurrent training (i.e., combination of endurance with strength training) may result in negative interference on strength performance. Moreover, there are indications that the magnitude of this interference is dependent on endurance exercise mode. PURPOSE: The purpose of this study was to compare maximal strength gains and acute volume performed during strength training (ST) and concurrent training (CT) consisting of high-intensity intermittent training plus strength training over the course of a 12-week intervention. METHODS: Nineteen recreationally active males were divided in CT (n=11) and ST (n=8) groups. The CT group performed repeated 1 min efforts at 100% of maximal aerobic velocity interspersed by 1 min of passive recovery until accumulating a total running distance of 5km followed by a strength session (consisting of three sets of eight exercises with loads of 8-12 repetition maximum) twice weekly for a period of 12 weeks, while the ST group performed only strength training sessions. Maximal strength and training volume during an acute exercise session were evaluated at baseline and after eight and 12 weeks of training. A two-way analysis of variance (group and training period) with repeated measures in the second factor was conducted to compare maximal strength values. A three-way analysis of variance (group, training period and set) was conducted to compare the volume performed in the acute exercise sessions. RESULTS: A small interference effect was observed in maximal strength relative to body mass after 12 weeks of training with greater improvements in the ST group compared to the CT group, that were not observed after 8 weeks. The volume performed during the acute exercise session was lower in CT than ST after 8 and 12 weeks of training. In summary, executing high-intensity intermittent exercise before strength training impaired the total volume performed after 8 and 12 weeks compared with strength training alone but the impairment of maximal strength occurred only after 12 weeks. CONCLUSION: These results suggest that the impairment of volume performed did not have an impact on strength gains until after 8 weeks of concurrent training with high-intensity intermittent exercise.

認知功能的提升是當今神經科學領域中的研究重點之一，但其神經機制尚有待釐清。本研究利用一種用於改善阿茲海默症臨床的非競爭型N-甲基-D-天門冬胺酸受體拮抗劑memantine，檢測其對於大白鼠在不同時距相關操作式制約行為及空間工作記憶行為之影響效果。實驗一為針對時間屬性的操作式制約行為實驗，運用大白鼠的區辯性增強低頻反應作業（DRL 10秒行為）與固定時距作業（FI 30秒行為）之行為作業，並操弄連續訓練與間歇訓練的兩種不同模式，測試memantine對前述四組受試的操作式制約行為在表現、消除與自發恢復等三階段之劑量反應。實驗二利用配對性延遲T迷津作業區分出不等基準線(表現好與表現差)之受試，再加以藥理實驗，測試memantine對於前述兩組受試之劑量反應。實驗一結果顯示，受試在兩種不同訓練模式下經十五次習得訓練後，在兩種操作式壓桿行為的壓桿反應相關指標中都有明顯的差異，這證實不同的行為訓練模式會導致學習後的表現有差異之別。memantine藥理實驗結果顯示，此藥對於上述四組受試的操作式行為之三階段的影響效果，會因為不同訓練模式與不同作業而異。實驗二結果顯示，memantine提高空間工作記憶的正確率在表現不好的組別有很顯著的藥效，這證實memantine對於空間式工作記憶行為的影響，也會因學習基準線的不同水平而異。在行為實驗後所進行的蛋白質表現量檢測中，memantine（5 mg/kg）只對五個測試腦區中的背側紋狀體中ERK1磷酸化程度有明顯上升的影響，而其對ERK2及CREB的磷酸化在所有腦組織中皆沒有顯著的影響。綜合以上結果，memantine影響時間與空間屬性的相關行為之藥理效果，會依行為的不同習得歷程(或行為背景經驗)及基準線表現程度而異，而此項行為藥理效果，可能與紋狀體中ERK1的磷酸化有關。 / The neural basis of cognitive enhancement is one of the intriguing topics in neuroscience research; however, the underlying neural mechanisms remain to be elucidated. This study examined the effects of memantine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which is used to treat Alzheimer’s disease in clinic, on operant behaviors and spatial working memory. In Experiment 1, using the differential reinforcement for low-rate-response 10 sec (DRL 10s) and the fixed-interval 30 sec (FI 30s) operant tasks, and with the manipulation of two different training regimens (continuous vs. intermittent) in the acquisition phase, the effects of memantine were evaluated in three stages of behavioral tests including the performance (right after the end of 15-day acquisition), the extinction, and the spontaneous recovery (after the extinction). In Experiment 2, memantine were tested in the subjects with different level of baseline performance (good vs. bad) on the distinctive patterns of operant responding in four different groups which received DRL 10s and FI 30s with different training regimens; indicating that behavioral task and training background are critical to the operant performance of temporal operant behaviors. Such behavioral outcomes led the dissociable effects of memantine appeared in between the four groups as tested in all three different stages. The results of Experiment 2 showed a profound improvement of the correct responses rate on spatial working memory in the low-baseline group as compared to the higher-baseline group. With a pretreatment of memantine (5 mg/kg), brain tissues in five selected areas were collected for western blot assays of ERK 1, ERK 2, and CREB. The results only revealed a significant increase of ERK 1 phosphorylation in the dorsal striatum. Together, the effects of memantine to improve cognition-associated processes in the temporal operant behaviors and the baseline of performance, and the present observation of cognition-enhancing effects of memantine may be resulted by the ERK 1 phosphorylation in the dorsal striatum.