Tambaqui (Colossoma macropomum) is the largest native Characiform species from the Amazon and Orinoco river basins of South America. Tambaqui farming is growing rapidly in Brazil, its production reached 139.209 tons in 2014, what corresponds to 57.7% of increase compared with 2013. However, few genetic studies of tambaqui are currently available. The tambaqui genetic studies for cultured and wild populations need a holistic approach for a rational action facing ecological and market challenges in aquaculture. Approaches based on genetic studies have provided important tools to understand population dynamics, local adaptation, and gene function to improve selection strategies to be applied in breeding programs. The next-generation sequencing (NGS) allowed a great advance in genomic and transcriptomic approaches, especially related to non-model species. The genotype-by-sequencing (GBS) is one of this approaches based on genome complexity reduction using restriction enzymes (REs). This thesis presents the application of these approaches to provide advances in the genetic background for tambaqui studies. The GBS approach provided a high-density SNPs panel that allowed us to develop the first linkage map, and association studies with environmental variables, local adaptation, and lack of intermuscular bones, both using tambaqui as a model. This work can give us many theoretical references to be applied in genetic breeding programs for tambaqui, allowing a better understanding of genetic processes related to traits of interest in aquaculture. / O tambaqui (Colossoma macropomum) é a maior espécie nativa de Characiforme da América do Sul e é encontrado nas bacias do rio Amazonas e Orinoco. O cultivo do tambaqui está crescendo rapidamente no Brasil, sua produção atingiu 139.209 toneladas em 2014, o que corresponde a 57,7% de aumento em relação a 2013. No entanto, poucos estudos genéticos realizados com o tambaqui estão disponíveis atualmente. Estudos genéticos em tambaqui, tanto em populações cultivadas quanto em populações selvagens, necessitam de uma abordagem holística para uma ação racional frente aos desafios ecológicos e mercadológicos na aquicultura. Abordagens baseadas em estudos genéticos têm fornecido ferramentas importantes para se entender a dinâmica populacional, adaptação local e função gênica visando melhorar as estratégias de seleção a serem aplicadas em programas de melhoramento genético. O sequenciamento de nova geração (NGS) permitiu um grande avanço nas abordagens genômicas e transcriptômicas, especialmente relacionadas a espécies não-modelo. A genotipagem por sequenciamento (GBS) é uma dessas abordagens que utilizam enzimas de restrição (REs) para reduzir a complexidade do genoma. Esta tese apresenta a aplicação desta abordagem objetivando proporcionar avanços significativos nos estudos genéticos de base para tambaqui. A técnica de GBS forneceu um painel de SNPs de alta densidade que nos permitiu desenvolver o primeiro mapa de ligação e estudos de associação com variáveis ambientais, adaptação local e ausência de ossos intermusculares no tambaqui. Este trabalho pode nos dar muitas referências teóricas a serem aplicadas em programas de melhoramento genético do tambaqui, permitindo uma melhor compreensão dos processos genéticos relacionados a traços de interesse na aquicultura.

Tambaqui (Colossoma macropomum) is the largest native Characiform species from the Amazon and Orinoco river basins of South America. Tambaqui farming is growing rapidly in Brazil, its production reached 139.209 tons in 2014, what corresponds to 57.7% of increase compared with 2013. However, few genetic studies of tambaqui are currently available. The tambaqui genetic studies for cultured and wild populations need a holistic approach for a rational action facing ecological and market challenges in aquaculture. Approaches based on genetic studies have provided important tools to understand population dynamics, local adaptation, and gene function to improve selection strategies to be applied in breeding programs. The next-generation sequencing (NGS) allowed a great advance in genomic and transcriptomic approaches, especially related to non-model species. The genotype-by-sequencing (GBS) is one of this approaches based on genome complexity reduction using restriction enzymes (REs). This thesis presents the application of these approaches to provide advances in the genetic background for tambaqui studies. The GBS approach provided a high-density SNPs panel that allowed us to develop the first linkage map, and association studies with environmental variables, local adaptation, and lack of intermuscular bones, both using tambaqui as a model. This work can give us many theoretical references to be applied in genetic breeding programs for tambaqui, allowing a better understanding of genetic processes related to traits of interest in aquaculture. / O tambaqui (Colossoma macropomum) é a maior espécie nativa de Characiforme da América do Sul e é encontrado nas bacias do rio Amazonas e Orinoco. O cultivo do tambaqui está crescendo rapidamente no Brasil, sua produção atingiu 139.209 toneladas em 2014, o que corresponde a 57,7% de aumento em relação a 2013. No entanto, poucos estudos genéticos realizados com o tambaqui estão disponíveis atualmente. Estudos genéticos em tambaqui, tanto em populações cultivadas quanto em populações selvagens, necessitam de uma abordagem holística para uma ação racional frente aos desafios ecológicos e mercadológicos na aquicultura. Abordagens baseadas em estudos genéticos têm fornecido ferramentas importantes para se entender a dinâmica populacional, adaptação local e função gênica visando melhorar as estratégias de seleção a serem aplicadas em programas de melhoramento genético. O sequenciamento de nova geração (NGS) permitiu um grande avanço nas abordagens genômicas e transcriptômicas, especialmente relacionadas a espécies não-modelo. A genotipagem por sequenciamento (GBS) é uma dessas abordagens que utilizam enzimas de restrição (REs) para reduzir a complexidade do genoma. Esta tese apresenta a aplicação desta abordagem objetivando proporcionar avanços significativos nos estudos genéticos de base para tambaqui. A técnica de GBS forneceu um painel de SNPs de alta densidade que nos permitiu desenvolver o primeiro mapa de ligação e estudos de associação com variáveis ambientais, adaptação local e ausência de ossos intermusculares no tambaqui. Este trabalho pode nos dar muitas referências teóricas a serem aplicadas em programas de melhoramento genético do tambaqui, permitindo uma melhor compreensão dos processos genéticos relacionados a traços de interesse na aquicultura.

El principal objectiu d'aquesta Tesi Doctoral ha estat caracteritzar el teixitadipós del Temasco de Aragón determinant el repartiment, la distribució, el continguten lípids totals i la composició dels mateixos. Al mateix temps s'ha estudiat l'efectede la raça, el grau d'engreixament i l'estat de conformació sobre les característiquesdel teixit adipós. S'han utilitzat 24 animals mascles, 8 de la raça Rasa Aragonesa, 8de la raça Roya Bilbilitana i 8 de la raça Ojinegra de Teruel. Els animals es vansacrificar al pes establert per la Denominació Específica (21 kg de pes viu perobtenir canals de 10,5 kg). Amb posterioritat al sacrifici es va realitzar la dissecciócomplerta de la mitja canal esquerra obtenint tots els dipòsits adiposos de l'animal(viscerals, cavitaris, subcutanis, intermusculars i els músculs) i es va determinar elcontingut en lípids totals i la seva composició. S'han trobat diferències en elcontingut dels lípids totals segons el repartiment del teixit adipós ( teixit cavitari94,9%, teixit visceral 86,7%, teixit subcutani 86,6%, teixit intermuscular 79,0% imúsculs 12,4%). S'ha constatat que la distribució també afecta el contingut de lípidstotals. Per altra banda s'han trobat diferències en la composició dels lípids totalssegons la distribució del teixit adipós. Segons la raça de procedència varia elcontingut i el repartiment del teixit adipós i també la raça afecta el contingut en lípidstotals i la seva composició. De forma global, la raça Rasa Aragonesa ha presentat elcontingut menor de teixit adipós i lípids totals i un major contingut en àcids grassosinsaturats (C16:1 i C18:1). La raça Ojinegra de Teruel ha presentat un contingutsuperior de teixit adipós i lípids totals amb un contingut superior d'aquests en àcidsgrassos saturats ( C16:0 i C 18:0) i la raça Roya Bilbilitana ha presentat unescaracterístiques intermèdies a les dues anteriors.

STUDY 1 Aim: To compare the effects of Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) on changes in bone mineral density (BMD), weight loss and blood biomarkers related to bone turnover, hormonal, and nutrient status. Subjects: Nine bariatric surgery patients. Methods: Patients had a DXA bone scan and fasting blood draw at baseline, three, and six months following surgery. Results: RYGB patients had greater weight loss vs. LAGB at both three (mean loss: 19 vs. 9%) and six months (26 vs. 11%), p<0.01. RYGB patients lost an average of 7% hip BMD at six months. Hip BMD loss at six months was correlated to decreased leptin (r=0.88) and increased adiponectin (r=-0.82), p<0.05. Bone turnover was indicated by elevated serum bone biomarkers after surgery. Conclusions: Research with larger sample sizes is warranted to better evaluate potential implications for late-life osteoporosis risk following bariatric surgery. STUDY 2 Aim: To determine repeatability for IMAT and muscle density, to evaluate the distribution of foreleg muscle and fat indices measured by pQCT and to determine predictors of muscle density and type-2 diabetes risk. Subjects: 82 women with varying BMI and physical activity levels. Methods: Subjects had DXA and pQCT bone scans, a fasting blood draw, and completed a 4-day physical activity record. Results: Fat and muscle distribution in the foreleg was highly correlated to total and central body adiposity. The pQCT device reliably measured muscle density (CV=0.8%), thus justifying use as surrogates for IMAT. Muscle density was positively related to physical activity (r=0.29; p<0.05) and negatively associated with markers of fat distribution and risk for type-2 diabetes [HOMA-IR (r=-0.44, p<0.01)]. Conclusions: Further research is necessary to determine whether specific fat or muscle depots can be targeted through exercise training to help with the prevention and treatment of obesity or type-2 diabetes. / Ph. D.

<p>Obesity has ascended to become the primary modifiable cause of death in the United States. New evidence has called into question the utility of BMI – the typical index of obesity – in predicting cardiometabolic disturbances. The distribution of body fatness may be just as important as the total quantity. Intermuscular adipose tissue (IMAT) has emerged as a distinct subset of adipose in skeletal muscle that may be particularly metabolically deleterious. Typically, sections of either the calf or thigh are used as proxy measurements for whole-body IMAT in investigations. However, IMAT dispersion may not be consistent across tissues, instead infiltrating specific muscle or muscle compartments, and these have may have different metabolic consequences. The study described in Chapter 2 was designed to address this possibility and investigate and compare associations among thigh and calf IMAT stores with indices of cardiometabolic health. The strength of the relationship between IMAT and glucose control-related indices of cardiometabolic health was dependent upon anatomic location. Specifically, thigh IMAT is a better predictor of cardiometabolic risk that calf IMAT. </p> <p>Skeletal muscle has gained increased recognition in recent years for its importance in promotion of health and wellness throughout the life course. While treatment models addressing issues of declining muscle mass and strength with age previously focused on older adults, the importance of utilizing a life course model to promote skeletal muscle health at all ages was more recently recognized. There is consistent evidence that higher-protein diets modestly improve body composition. However, women are at greater risk for not meeting protein requirements and seem to be less willing to adopt strategies to achieve greater protein intake, such as protein supplementation, for fear that it may cause ‘bulkiness’. Therefore, the study described in Chapter 3 was designed to critically evaluate the effect of whey protein supplementation on body composition changes in women via a systematic review & meta-analysis of published randomized controlled trials. It was hypothesized that whey protein supplementation would moderately improve body composition but would not cause excessive muscle hypertrophy. Consistent with our hypothesis, whey protein supplementation improved body composition by modestly (<1%) increasing lean mass, without influencing fat mass.</p> <p>Dietary protein and skeletal muscle are conceptually inseparable; protein is often only considered in terms of how it impacts skeletal muscle-related outcomes. However, it is of interest to determine if the proposed beneficial effects of increased dietary protein consumption extend beyond skeletal muscle. Consumption of higher protein diets result in lower resting blood pressure, but the potential for protein to attenuate acute exercise blood pressure responses is unclear. The study described in Chapter 4 was designed to investigate the effects of meals with different amounts of protein on blood pressure responses to exercise in a randomized, cross-over trial. We hypothesized that consuming the higher-protein meal would attenuate the blood pressure responses to exercise and result in a more robust post-exercise hypotensive response. Contrary to our hypothesis, a higher-protein meal does not attenuate exercise-induced blood pressure responses compared to a lower-protein meal. These findings build upon previous research suggesting that the beneficial effect of chronically elevated protein intake on blood pressure is typically not observed in an acute setting by extending these findings to encompass blood pressure responses to acute responses to exercise.</p> <p>The three studies packaged herein utilize different techniques and report on different outcomes, but conceptual threads unite these works which augment the collective findings. Future researchers investigating the effects of protein on skeletal muscle anabolism can: 1) learn of the importance of proper reflection on surrogate measures and potential for anatomic-specific effects from the IMAT findings (Chapter 2), 2) appreciate the relevance of energy and training states in modulating responses from the WP meta-analysis (Chapter 3), and 3) recognize the importance of holistic approaches and employing challenges to reveal heterogeneity from the protein and BP trial (Chapter 4). Taken together, the research presented in this dissertation forwards our understanding of the relations and effects of dietary protein with different components of body composition on cardiometabolic health. </p>

Le corps humain possède une grande redondance musculo-squelettique, se traduisant par une infinité de coordinations musculaires possibles pour produire un effort résultant. Lors d'un mouvement, le système nerveux central est confronté à la gestion de cette redondance. A travers l’analyse de cohérence entre les signaux électromyographiques, ce travail de thèse étudie le rôle fonctionnel du couplage intermusculaire et explore la contribution des mécanismes nerveux impliqués dans la régulation de la redondance musculaire en termes de contrôle de l’activité des muscles agonistes, et antagonistes impliqués dans le phénomène de co-contraction. Nos résultats ont révélé que le couplage intermusculaire entre deux muscles agonistes est modulé en présence de fatigue et en fonction de l’expertise sportive. De plus, le couplage entre muscles agonistes et antagonistes dépend des contraintes mécaniques et du rôle fonctionnel des muscles, et semble directement lié au niveau de co-contraction. La cohérence intermusculaire est modulée dans plusieurs bandes de fréquence, témoignant de l’implication de différentes commandes centrales communes d’origines spinales et supra-spinales. Nos conclusions amènent à penser que la coordination musculaire est en partie contrôlée par des commandes nerveuses communes dont la contribution est modulée suivant les propriétés fonctionnelles des muscles concernées, pour s’adapter de manière optimale aux contraintes internes ou externes de la tâche. Les travaux déjà engagés proposent de contribuer à une meilleure compréhension des mécanismes sous-jacents l’altération de la fonction motrice chez des patients cérébro-lésés. / The human motor system is characterized by high musculoskeletal redundancy, implying that a given resultant effort can result from infinity of feasible muscle coordinations. During a movement, the central nervous system has to manage such redundancy. Through coherence analysis between electromyographic signals, this thesis work aims at investigating the functional role of intermuscular coupling and at better understanding the contribution of central nervous mechanisms responsible for the regulation of muscle redundancy, in terms of agonist muscle activity and also antagonist muscles activity involved in co-contraction. Our results revealed that intermuscular coupling between agonist muscles is modulated according to both the fatigue level and the training status. We also showed that the coupling between agonist and antagonist muscles depends on the mechanical configuration and functional role of muscle pairs, and seems directly related to co-contraction. The modulation of intermuscular coherence occurs in several frequency bands, suggesting the involvement of different common central drives of spinal and supra-spinal origins according to task constraints. Taken together, our results lead us to conclude that common neural drives take part in the control of muscular coordination, with different relative contribution according to the functional properties of recruited muscles, in order to optimally adapt to both internal and external task contraints. Work already undertaken proposes to provide a better understanding of the mechanisms underlying impairment of motor function in brain-injured patients.