Metabolic syndrome (MetS) and abdominal obesity (AbOb) increase the risk of developing cardiovascular disease and diabetes. Energy restriction (ER), highprotein (PRO) intake and high-intensity interval training (HIT) can independently improve MetS and AbOb. However, ER reduces metabolically active lean body mass (LBM) in addition to body fat (BF). Purpose: To determine the effects of a 16-wk ER diet with 2 levels of PRO (15% or 25% of energy), plus HIT, on MetS risk factors, AbOb, and body composition in women. Methods: Sedentary, premenopausal women (age=35±10y) with AbOb (waist circumference [WC] ≥80cm) were randomized to a 16-wk ER diet (-300kcals/d) with 15% (15PRO; n=17) or 25% (25PRO; n=18) of energy from PRO, plus 45min/d, 3d/wk HIT and 45min/d, 2d/wk continuous moderate-intensity exercise (CME) (-200kcals/d). Diet and physical activity (PA) were assessed using 4-d weighed food and PA records, respectively; diet and exercise compliance were assessed monthly with multiple-pass 24-h recalls and weekly tracking logs. Body weight (BW), WC, DXA-assessed body composition (BF [%], BF [kg], trunk fat [kg], and LBM [kg]), blood lipids (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides [TG]), glycemic markers (fasting plasma glucose [FPG], insulin, and homeostatic model assessment for insulin resistance [HOMA-IR], beta cell function [HOMA-%β] and insulin sensitivity [HOMA-%S]) and resting blood pressure (BP) (systolic BP [SBP]; diastolic BP [DBP]) were assessed pre/post-intervention. Repeated measures analysis of variance and two sample t-tests were used at analyze the date. Results are reported as means±standard deviations. Results: There were significant time, but not group, differences in BW (-5.1±2.6kg, p=0.0141), WC (- 7.3±3.6cm, p<0.0001), TC (-18.1±17.4mg/dL, p<0.0001), LDL-C (12.2± 16.2mg/dL, p<0.0001), TG (-25.3±56.2mg/dL, p=0.0064), insulin (-2.1±4.2mg/dL, p=0.0048), HOMA-IR (-0.2±0.5, p=0.0062), HOMA-%β (-12.1±35.2%, p=0.0497), HOMA-%S (28.5±78.4%, p=0.0357), and SBP (-3±9mmHg, p=0.214). There were significant group x time differences in DBP (15PRO=-5±8mmHg, 25PRO=- 2±8mmHg; p=0.0024). There were no time or group differences in FPG or HDLC. There were significant time, but not group, effects on changes in BW (-5.1kg± 2.6, p<0.0001), BF (-3.3±1.6%, p<0.0001), and LBM (-0.6kg±1.5, p=0.0283). The 15PRO group lost more absolute whole BF (-5.2kg vs. -3.9kg, p=0.0355) and trunk fat (-3.1kg vs. -2.2kg) vs. the 25PRO group. Conclusion: Both diets significantly improved BW, AbOb, MetS risk factors, glycemic control, and BF (%); LBM (kg) loss was similar in both groups. Compared to the 15PRO diet had significantly greater absolute BF-kg and trunk fat-kg losses. Increased PRO intake did not improve AbOb or MetS risk beyond ER and HIT/CME. The impact of HIT/CME and the greater (-1.3kg) changes in BW in the 15PRO group may have contributed significantly to the changes in absolute BF and trunk fat. More research is needed to separate the impact of HIT/CME and weight loss from the impact of PRO during ER. / Graduation date: 2013 / Access restricted to the OSU Community at author's request from March 28, 2013 - March 28, 2014

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

Le diabète de type 1 (DT1) est une maladie complexe qui requiert une implication importante des patients pour contrôler leur glycémie et ainsi prévenir les complications et comorbidités. L’activité physique (AP) régulière et une attention constante pour les glucides ingérés sont des adjuvants essentiels au traitement insulinique. Nous avons démontré que le questionnaire BAPAD-1, spécifiquement développé pour des adultes atteints de DT1, est un outil valide (validité prédictive, fiabilité interne et reproductibilité) pour définir des barrières associées à l’AP. Bien que le niveau de barrières envers l’AP soit faible, la crainte de l’hypoglycémie est la barrière la plus importante chez cette population. L’adoption d’un mode de vie actif est associée à un profil corporel favorable. Les adultes, avec un DT1 et non diabétique, qui maintiennent un bon niveau d’AP, soit un ratio entre la dépense énergétique totale et celle au repos ≥ 1.7, ont une masse grasse, un indice de masse corporelle et un tour de taille significativement inférieurs à ceux d’adultes moins actifs. Le niveau d’AP peut être estimé au moyen d’un moniteur d’AP comme le SenseWear Armband™. Afin de compléter les études de validation de cet outil, nous avons évalué et démontré la reproductibilité des mesures. Toutefois, la dépense énergétique est sous-estimée durant les 10 premières minutes d’une AP d’intensité modérée sur ergocycle. L’utilisation de cet appareil est donc justifiée pour une évaluation de la dépense énergétique sur de longues périodes. Le calcul des glucides est une méthode largement utilisée pour évaluer la quantité d’insuline à injecter lors des repas. Nous avons évalué dans un contexte de vie courante, sans révision de la technique, la précision des patients pour ce calcul. L’erreur moyenne est de 15,4 ± 7,8 g par repas, soit 20,9 ± 9,7 % du contenu glucidique. L’erreur moyenne est positivement associée à de plus grandes fluctuations glycémiques mesurées via un lecteur de glucose en continu. Une révision régulière du calcul des glucides est probablement nécessaire pour permettre un meilleur contrôle glycémique. Nous avons développé et testé lors d’un essai clinique randomisé contrôlé un programme de promotion de l’AP (PEP-1). Ce programme de 12 semaines inclut une séance hebdomadaire en groupe ayant pour but d’initier l’AP, d’établir des objectifs et d’outiller les adultes atteints de DT1 quant à la gestion de la glycémie à l’AP. Bien que n’ayant pas permis d’augmenter la dépense énergétique, le programme a permis un maintien du niveau d’AP et une amélioration de la condition cardio-respiratoire et de la pression artérielle. À la fin du programme, une plus grande proportion de patients connaissait la pharmacocinétique de l’insuline et une plus grande variété de méthodes pour contrer l’hypoglycémie associée à l’AP était utilisée. En conclusion, le diabète de type 1 engendre des défis quotidiens particuliers. D’une part, le calcul des glucides est une tâche complexe et son imprécision est associée aux fluctuations glycémiques quotidiennes. D’autre part, l’adoption d’un mode de vie actif, qui est associée à un meilleur profil de composition corporelle, est limitée par la crainte des hypoglycémies. Le programme PEP-1 offre un support pour intégrer l’AP dans les habitudes de vie des adultes avec un DT1 et ainsi améliorer certains facteurs de risque cardio-vasculaire. / Type 1 diabetes (T1D) is a complex disease requiring continuous self-management. Physical activity (PA) and carbohydrate counting are essential counterparts to insulin therapy for blood glucose control in order to prevent complications and comorbidities. We have demonstrated the validity (predictive validity, internal validity and reproducibility) of the BAPAD-1 scale to assess perceived barriers associated with PA practice. Fear of hypoglycemia is the strongest perceived barrier among adults with T1D. An active lifestyle, as described by a physical activity level (ratio of total over resting energy expenditure) ≥ 1.7, is associated with a better body composition compared to less active adults. Adults who are more active show significantly less fat mass, smaller body mass index and smaller waist circumference. Motion sensors, like the SenseWear Armband™, are useful to estimate PA level. To complement prior validation studies, we evaluated and confirmed the reproducibility of the SenseWear Armband™ measurements. However, we also observed that energy expenditure is underestimated at the onset of moderate intensity ergocycling. Thus, this motion sensor should be used to evaluate energy expenditure over long periods of time rather than short length exercise. Carbohydrate counting is a widely used method to evaluate prandial insulin doses. We evaluated, in a real-life setting without prior method revision, the accuracy of adults with T1D for carbohydrate estimation. The mean meal error was 15.4 ± 7.8 g or 20.9 ± 9.7 % of total carbohydrate content. The mean meal error was positively associated with larger daily glucose fluctuations measured by a continuous glucose monitoring system. Regular educational tips regarding carbohydrate counting may be necessary to improve glycemic control. In order to improve PA practice, we developed and tested in a randomized controlled trial a PA promotion program (PAP-1). This 12-week program includes a weekly group session designed for PA initiation, goal setting and improving knowledge about glycemic control during PA. Even if the program failed to improve total energy expenditure, participants improved their cardiorespiratory fitness and blood pressure. At the end of the program, a larger proportion of the participants were knowledgeable of insulin pharmacokinetics and they used more various methods to prevent hypoglycemia related to PA. In conclusion, type 1 diabetes obtrudes many daily challenges. On one hand, carbohydrate counting is a complex job and its inaccuracy is associated with glycemic fluctuations. On the other hand, even if having an active lifestyle is associated with a better body composition, fear of hypoglycaemia may impede PA practice. The PAP-1 program offers support to adults with T1D to adopt an active lifestyle and thus improve some cardivascular risk factors.

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.

Global obesity is linked to chronic diseases including hypercholesterolemia, a cardiovascular disease risk factor, thus weight reduction in obesity is a key priority for combatting obesity. The cholesterol transporters ABCG5, ABCG8 and NPC1L1 mediate cholesterol trafficking across the intestinal wall, thus are important in regulating cholesterol metabolism and circulating levels. The objective of this study was to examine if single nucleotide polymorphisms (SNP) of cholesterol transporters ABCG5, ABCG8 and NPC1L1 are associated with changes in cholesterol synthesis and absorption and lipid parameters (LP) subsequent to weight loss (WtL) in overweight individuals. Eighty-nine individuals from two WtL trials (Trial A (n = 54) and Trial B (n = 35)) completed a 20-wk WtL period. After 10% WtL, lipid parameters excluding LDL-C were improved in Trial A, while all lipid parameters were ameliorated after 12% of WtL when Trial A and B were combined. Post-WtL, cholesterol synthesis (CS) was reduced; however, cholesterol absorption was not changed in either Trial A or the combined trials. Polymorphisms in ABCG8 V632A were associated with changes in TC and TG levels after WtL in both trial A and the combined data. SNPs in ABCG5 Q604E, ABCG8 T400K, were associated with changes in CS because of WtL in Trial A; however, the association is no longer seen in combined analysis. In conclusion, cardio-protective changes in LP due to weight loss were mediated by reductions in CS. Additionally, polymorphisms in ABCG8 were associated with amelioration in LP after WtL. Thus, the benefits in CVD risk subsequent to weight loss vary across individuals due to genetic factors associated with cholesterol trafficking.

The primary objective of this PhD program was to investigate the impact of training at a constant-load moderate-intensity (FATmax) compared to work-matched high-intensity intervals (HIIT) on the metabolic, physiological and psychosocial health profiles of sedentary overweight and obese men. This study was unique in that it was the first time the effect of exercise intensity had been investigated to examine concurrently the components of whole-body energy metabolism and body composition as measured using gold standard techniques. Based upon the positive alterations in blood lipids, body composition, cardiorespiratory fitness and substrate oxidation, it appears that training at FATmax can positively impact health parameters as well as, or if not better than, high-intensity training. Furthermore, there are ramifications for public health messages and obesity management strategies arising from these findings, primarily attributable to the increased exercise adherence and the reduction in health risks stemming from the significant loss of abdominal visceral adipose tissue after FATmax training.

This thesis describes two approaches for studying of lipoprotein metabolism in sheep. The first approach involves the assay of lipoprotein lipase (LPL) activity to determine the role of lipoprotein-triacylglycerol fatty acids in fat deposition in sheep. This enzyme is the rate limiting enzyme in the hydrolysis of fatty acids from lipoprotein-triacylglycerol. The second approach was to characterize and quantify in vivo lipoprotein metabolism using iodinated very low density lipoprotein (¹²⁵I-VLDL) and low density lipoprotein (¹³¹I-LDL). Cross-bred lambs were divided into two treatment groups and either weaned early at 5 weeks of age or remained suckling. Lambs were slaughtered at 12 or 23 weeks at which time the body composition and adipose tissue LPL activity were determined. The differences in rearing led to differences in body composition. The suckled lambs were larger and fatter than weaned lambs. The increased fatness in the suckled lambs was associated with increased LPL activity (U/mg protein) in subcutaneous adipose tissue and was reflected in higher LPL activity in post-heparin plasma (PHP) taken 2 days prior to slaughter. The role of insulin in the regulation of LPL activity was investigated by either infusing a subset of the weaned and suckled lambs with insulin for 7 or 18 weeks or using the euglycemic clamp technique to study the effect of short insulin infusions. The long term infusion of insulin had no significant effect on PHP LPL or on adipose tissue LPL (U/g tissue). However, after infusing insulin for 6h at 6.3 mU.kg⁻·⁷⁵.h⁻¹ during the euglycemic clamps, a two fold increase in LPL activity in biopsied subcutaneous adipose tissue was observed. In the second approach, in vivo lipoprotein metabolism was investigated in 4 lambs using apolipoprotein B as a marker. Following the simultaneous injection of ¹²⁵I VLDL and ¹³¹I VLDL, the specific activities of apoB in VLDL, IDL and LDL fractions were determined. ApoB specific activity curves demonstrated that VLDL is metabolised to IDL and subsequently to LDL. The turnover of VLDL-B (3.45mg.d⁻¹.kg⁻¹) and LDL-B (4.8mg.d⁻¹.kg⁻¹) was calculated by fitting the VLDL-¹²⁵I-B and LDL-¹³¹I-B specific activity data to a mono-exponential equation. The metabolism of lipoproteins, inferred from the study of apoB, was shown to be similar in sheep to that reported in other animals although the amount of lipoprotein synthesised was low. A model to describe the kinetics of apoB metabolism in sheep was developed using SAAM. The proposed model features a three pool delipidation chain for VLDL, and subsystems containing two pools for IDL and LDL. IDL may be catabolised to LDL or cleared directly from the plasma. The developed model can now be used to compare the metabolism of lipoproteins in different physiological states and to design new experiments to study lipoprotein metabolism further.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

O excesso de gordura corporal esta associado a diversas doenças de ordem metabólica, psicológica e estrutural. É indicado que a adolescência é o período crítico para o desenvolvimento de hábitos associados ao acúmulo de gordura como a inatividade física, má alimentação e sedentarismo. Desta forma, esta é uma fase crítica para o monitoramento da população visando a redução de casos de obesidade e doenças associadas. A técnica padrão-ouro para avaliação da gordura corporal é a absorciometria de raios-X de dupla-energia. Porém seu caráter laboratorial impede o uso amplo. Desta forma, técnicas mais simples, como a medição de dobras cutâneas devem ser modeladas a partir de técnicas mais exatas para este monitoramento. Os modelos existentes foram desenvolvidos com populações estrangeiras que não se assemelham aos habitantes da Região Metropolitana de Curitiba o que pode levar a erros de avaliação e diagnóstico. Desta forma o objetivo deste estudo é produzir um modelo de análise da gordura corporal apropriado a crianças e adolescentes da Região Metropolitana de Curitiba. Foram selecionadas duas amostras, uma composta por 567 adolescentes hígidos com idade entre 10 e 18 anos; e outra composta por 63 crianças com paralisia cerebral entre 3 e 10 anos. Os dois grupos possuíam indivíduos de ambos os sexos. Foram coletados dados de massa, estatura, idade e espessura de dobras cutâneas, além da avaliação de composição corporal por densitometria radiológica. O percentual de gordura obtido por diferentes equações de dobras cutâneas e demais medidas antropométricas entre os adolescentes foi comparado com o obtido por densitometria indicando associações abaixo do indicado (CCC<0,900). Foi encontrada também uma tendência de subestimação pelas dobras cutâneas, o que resultava em elevados valores de especificidade e baixos de sensibilidade (sendo especificidade á quantidade relativa de verdadeiros negativos entre quem não possui a condição clínica, e a sensibilidade a relação de verdadeiros positivos entre quem possui a condição considerada). Isto indica uma grande quantidade de falsos negativos o que leva muitos adolescentes com excesso de gordura a serem classificados como eutróficos. O modelo classificatório desenvolvido para adolescentes obteve um ajuste de R2 Negelkerke=0,829, sensibilidade de 99,0% e especificidade de 82,7% apresentando indicadores diagnósticos acima do obtido por equações de dobras cutâneas e IMC. Para as crianças com paralisia cerebral foi desenvolvido um modelo estimativo da massa de gordura com ajuste de R2 =0,950 com erro padrão de estimativa de 1,039. As equações utilizadas para converter as dobras cutâneas em medições da gordura corporal demonstraram-se inadequadas para aplicação em adolescentes da região metropolitana de Curitiba. A aplicação de técnicas de regressão logística e linear apresentou resultados positivos, mesmo a partir da modelagem na amostra de crianças com paralisia cerebral. / The overfat is associated with many methabolic, psycological and structural diseases. The adolescence is indicated as the critical period for the development of habits associated with fat accumulation like physical inactivity, poor diet and sedentarism. Thus, this is a important moment to monitorig the population aiming the reduction of obesity and associated disease. The golden standard to evaluate the body fatness is the dual-energy x-ray absorptiometry. However, its laboratorial aspect prevents a wide use. This way, simpler techniques as the skinfold measurement should be model from more exact techniques for this monitoring. The existing models were developed with foreign populations that don't resemble the Curitiba Metropolitan Region habitants. This could lead to evaluation and diagnostic errors. Thus, the aim of this study is to product a model of body fatness analysis appropriate to children and adolescents from the Curitiba Metropolitan Region. Two sample were selected, the first one composed by 567 healthy adolescents aged between 10 and 18 years; the other one composed by 63 children with cerebral palsy between 3 and 10 years. The groups have both genders. The data of weight, height, age and skinfold thickness were collected, beyond the body composition evaluation by radiologic densitometry. The fatness percentage obtained by different skinfold and other anthopometric mesures equations among the adolescents was compared with the obtained by densitometry presenting associations below indicated (CCC<0,900). A tendency of underestimation by the skinfold equations was found, that resulted in higher specificity values and low sensitivity (being specificity the relative quantity of true negatives among those who do not have de clinical condition, and the sensitivity the relations of true positives amons those who have the considered condition). This indicates a major quantitaty of false negatives, that leads many overfat adolescents to be classify as eutrophic. The developed classificatory model for adolescents obtained an adjustment of R2 Negelkerke=0,829, sensitivity of 99,0% and specificity of 82,7% presenting diagnostic's indicators above that obtained by skinfold equations and BMI. For the children with cerebral palsy was developed a fat mass estimation model with adjustment of R2 =0,950 and standard error of estimative of 1,039. The equations used to convert the skinfold in body fatness measures were found to be inadequate for aplication in adolescents from Curitiba Metropolitan Region. The aplication of logistic and linear regression techniques have presented positive results, even from modeling in the children with cerebral palsy sample.

No description available.