Hydroxytyrosol (HT) has been found to be a potent antioxidant and hypocholesterolemic agent in various animal models of disease including dyslipidemia, atherosclerosis, and diabetes. Therefore, the purpose of this study was to examine the effects of hydroxytyrosol (HT) supplementation on the lipid profile and metabolic risk markers in recreationally active men. Sixty-one (n = 61) subjects (21.46 ± 0.22 yrs, 179.46 ± 0.79 cm, 78.91 ± 1.19 kg) consumed HT in either a high dose (HI, 150 mg HT; n = 22), a low dose (LO, 50 mg HT; n = 20), or a placebo (PLA; n = 19) every day for 6 weeks. Blood draws were obtained at baseline, 14, 28, and 39 days under fasting conditions. Analyzed were the components of the plasma lipid profile: total cholesterol (TC), high density lipoprotein cholesterol (HDLc), the TC:HDLc fraction, low density lipoprotein cholesterol (LDLc), very low density lipoprotein cholesterol (VLDLc), and triglycerides (Tg); and markers of metabolic risk: uric acid, lipase, hemoglobin (Hb), glycated hemoglobin (HbA1c), and blood glucose (BG). The primary finding was that HT, in either HI or LO dosages did not cause clinically meaningful changes in the blood lipid profile or markers of metabolic risk. Subjects in the HI group experienced a small big significant increase in fasting blood glucose, while those in the PLA group experienced a significant increase in VLDLc concentration. In both cases, however, the mean values remained within their respective healthy reference ranges. Whether these changes would persist beyond the 6-week course of this study is not known. While no improvements were seen in any of our selected measures, these results indicate that HT supplementation, ranging from 50 to 150 mg/day, is safe to consume for durations up to 6 weeks in healthy young men. By maintaining the lipid profile and metabolic risk markers within a healthy range, it is possible that HT may impart a degree of protection against cardiovascular and metabolic disease risk, but such an effect may only be apparent when the plasma lipid and/or metabolic risk profile is abnormal. / text

The aim of this thesis was to describe the relationships between energy expenditure and body composition in healthy adults and children and in patients with metabolic disorders. In a healthy population resting energy expenditure (REE) is highly influenced by body composition, specifically lean mass (LM). Prediction equations can therefore accurately predict REE from body composition in healthy individuals. However, application of these equations to clinical patients, in whom metabolism is disordered, risks miscalculation of energy metabolism due to their dissociation between body composition and energy expenditure. Therefore new prediction equations were derived based on precise body composition measurements in healthy adults and children. Then, in patients with metabolic disorders, differences between their measured and equation-predicted REE and LM were presented as standardised Z scores. REE in healthy adults was predicted by the coefficients: age, fat mass and fat-free mass. LM in healthy adults was predicted by the coefficients: bone mineral content and height2 in men; and by fat and height2 in women. In healthy children, REE was predicted using gender specific models: by fat and LM in boys; and by solely LM in girls. REE and LM were then measured in adult and paediatric patients with metabolic disorders (Lipodystrophy, Thyrotoxicosis and Resistance to Thyroid Hormone β or α), and Z scores were calculated to highlight their deviations from the healthy populations. In adults, thyrotoxicosis patients displayed the highest REE Z scores (5.8), followed by lipodystrophy (2.9) and RTHβ cases (1.8), with RTHα demonstrating the lowest REE Z scores (-2.3). For LM, lipodystrophy patients exhibited with the highest Z scores (4.2), followed by RTHα patients (2.1), with RTHβ patients showing normal LM Z scores (-0.2) and thyrotoxicosis patients presenting with the lowest LM Z scores (-1.2). In the paediatric patients, RTHβ patients demonstrated REE Z scores similar to healthy controls (males; -0.15, females; 0.15), but RTHα patients displayed lower REE Z scores (male; -0.82, female; -2.2) compared to RTHβ patients and healthy controls. These studies highlight the disassociation between REE and body composition in patients with metabolic disorders. The application of a prediction equation for REE to calculate Z scores between measured and predicted values allows quantification of the differences between patients with metabolic disorders and healthy populations, and is a new and important concept.

No description available.

L’obésité est caractérisée par un état inflammatoire chronique dit « à bas bruit », se traduisant par l’augmentation des taux plasmatiques de facteurs inflammatoires qui contribuent au développement des complications métaboliques telles que le diabète de type 2 et la résistance à l’insuline.L’inflammation chronique est initiée par l’accumulation séquentielle et finement régulée de cellules immunes dans le tissu adipeux blanc, contribuant à créer un microenvironnement inflammatoire qui altère la physiologie et l’homéostasie du tissu. Une meilleure compréhension : 1) des mécanismes contrôlant les altérations de la composition en cellules immunes du tissu adipeux blanc et 2) du rôle de ces cellules dans la fonction des principaux tissus métaboliques, pourrait, à terme, permettre de proposer de nouvelles voies thérapeutiques d’immuno-intervention dans le traitement des complications métaboliques associées à l’obésité. Durant mon parcours de thèse, j’ai étudié les conséquences métaboliques et immunologiques du traitement de souris obèses par un agent immuno-modulateur : la rapamycine, ainsi que par des probiotiques ayant des propriétés anti-inflammatoires.Partie 1 : Etude des effets de la rapamycine sur la réponse inflammatoire et l’homéostasie énergétique chez la souris obèse.Cette étude représente la partie principale de mon travail de thèse. L’objectif de mon projet de thèse était de définir les conséquences de l’administration prolongée de rapamycine (ou Sirolimus) sur l’inflammation du tissu adipeux blanc et le métabolisme glucidique de souris obèses. La rapamycine est un inhibiteur spécifique de la voie du mechanistic target of rapamycin (mTOR) possédant des propriétés immunosuppressives et antiprolifératives et qui est fréquemment utilisé chez les patients transplantés afin d’éviter le rejet du greffon. Cependant, la rapamycine a été décrite comme possédant un potentiel diabétogène et pro-inflammatoire : en effet, certains patients traités développent un diabète post-transplantation et sont plus susceptibles de présenter des pathologies inflammatoires et ceci, malgré une perte de poids. Les objectifs de notre étude étaient de : 1) Déterminer les conséquences métaboliques (bénéfiques ou délétères) de l’administration de rapamycine et 2) Définir le profil inflammatoire des souris obèses traitées, notamment dans le tissu adipeux blanc.Partie 2 : Etude des effets des probiotiques sur le développement de l’obésité et la résistance à l’insuline chez la souris obèse.Les effets des probiotiques sur le développement de l’obésité et ses complications métaboliques et immunologiques associées sont contradictoires et restent donc à clarifier. Certaines études ont montré des effets obésogènes de certains probiotiques tandis que d’autres travaux décrivent des effets bénéfiques sur l’homéostasie énergétique. Les objectifs de notre étude étaient de : 1) Déterminer les conséquences métaboliques et immunologiques de l’ingestion prolongée de certaines souches (ou combinaison de souches) de probiotiques dans un modèle de souris obèses et 2) Définir les mécanismes cellulaires et moléculaires sous-tendant les effets de probiotiques sur le développement de l’obésité et de l’inflammation associée. / Obesity is characterized by a low-grade chronic inflammation reflected by increased blood levels of inflammatory factors, which are known to contribute to the development of metabolic complications such as insulin resistance and type 2 diabetes.Obesity-related inflammation is initiated by the accumulation of inflammatory immune cells within the adipose tissue as observed in obese subjects, contributing to alteration of the physiology and the metabolic homeostasis of the tissue. A better understanding of the mechanisms controlling the balance between adipose tissue immune cells and the interaction of these cells with the metabolic tissues (e.g. white adipose tissue) could lead to the development of immune-based new therapeutic strategies to treat metabolic complications associated with obesity.During my PhD thesis, we worked on two projects that both aimed at studying the link between immunity and metabolism. We studied the consequences of the treatment of obese mice with the immunomodulatory drug rapamycin (Part 1) and with probiotics having anti-inflammatory properties (Part 2).Part 1: Beneficial Metabolic Effects of Rapamycin are Associated with Enhanced Regulatory Cells in Diet-Induced Obese MiceThis part corresponded to my main project. We aimed to analyze the effect of rapamycin (or Sirolimus), on the inflammatory response and the metabolic status of high-fat diet fed mice. Rapamycin is an immunosuppressive drug commonly used in transplanted patients to prevent graft rejection. However, the effects of rapamycin on metabolism remain elusive and it has been reported that rapamycin may have pro-inflammatory and prodiabetic properties since some transplanted patients can develop diabetes and inflammatory diseases. Rapamycin is a specific inhibitor of mTOR (mechanistic Target Of Rapamycin), a highly conserved kinase which play a key role in both metabolism and immunity. Our aims were: 1) to define the metabolic consequences of long-term rapamycin administration and 2) to analyze the immune profile of treated animals.Part 2: A Probiotic Mixture Alleviates Diet-Induced Obesity and Insulin Resistance in Mice through Adipose Tissue Cell-RemodelingThe effects of probiotics on the development of obesity and its associated-metabolic complications are contradictory and thus remain to be clarified. In our study, we evaluated the consequences of the consumption of different strains of probiotics (or a combination of strains) selected for their anti-inflammatory properties, on the development of obesity and inflammation. We thus defined the metabolic and immune profile of probiotic-treated obese mice, mostly focusing on the adipose tissue. Finally, we attempted to identify the cellular and molecular mechanisms by which our selected probiotics exerted their metabolic and immune protective effects.

Background: Generating evidence to inform care for pediatric medium-chain acyl-CoA dehydrogenase (MCAD) deficiency requires sustainable and integrated measurement of priority outcomes. Methods: From an existing Canadian cohort study, we evaluated the quality of metabolic clinic chart-abstracted data for measuring core outcomes for pediatric MCAD deficiency. We then modelled variation in emergency department (ED) use, in association with disease severity, child age, and distance to care. Results: Children with MCAD deficiency visit the metabolic clinic at least annually on average but we identified data quality challenges related to inconsistent definitions of core outcomes and missing information in patient charts. Rates of ED use were highest among children aged 6 to 12 months, with more severe disease, and living closest to care. Conclusion: While measuring core outcomes through the metabolic clinic for children with MCAD deficiency is feasible, harmonized data collection is needed to evaluate care and further understand ED use.

BACKGROUND: Periodontal disease is a major chronic disease worldwide and one of the most prevalent oral pathologies. Some factors that may lead to periodontal disease include poor nutrition, chronic illness, poor lifestyle choices, smoking, and excessive alcohol consumption. Previous studies have also revealed a biological link between diabetes or obesity and periodontal health status. Because physical activity can reduce the risk of diabetes and obesity, it would follow that physical activity may also lead to improved periodontal health. However, to date, there has been limited research on the effects of physical activity on periodontal disease risk. Our investigation answers the following question: Do people who are more physically active have better periodontal health than those who are inactive? OBJECTIVE: The purpose of our research initiative was to evaluate the prevalence of periodontal disease among people who are physically inactive versus those who are physically active using data from NHANES. METHODS: In this study, we utilized the publicly available NHANES 2011-2012 datasets of 9756 observations before exclusions. Our study included individuals (30-80 years of age) consisting of 49.4% male and 50.6% female who provided demographic data, periodontal and dentition examination data, and self-reported smoking and physical activity data (Table 3). There were a total of 3327 observations meeting our inclusion criteria. Weighted prevalence estimates and odds ratios (OR) were calculated for physical activity adjusted by age, gender, race, education level, and economic status. Physical activity was categorized by domains of transportation physical activity, occupation physical activity, leisure time physical activity, and sedentary behavior. Physical activity was also categorized into a dichotomous total amount of physical activity by adding the three major physical activity domains. RESULTS: We observed higher rates of periodontal disease in men, in older adults, smokers, and individuals with diabetes mellitus. We also observed that individuals with higher total physical activity and leisure time physical activity and lower amount of total sedentary activity had lower periodontal disease rates. After adjusting for confounders, lower sedentary time was associated with lower periodontal disease rates (OR 1.18; 95% CI (Confidence Interval) 1.01,1.38; p=0.0416), but total physical activity and leisure time was not significantly associated with periodontal disease (OR 1.00; 95% CI 0.79,1.28; p=0.98) (OR 1.14; 95% CI 0.81,1.61; p=0.42) (Table 5). CONCLUSION: Our findings indicate sedentary time is associated with higher rates of periodontal disease. Future prospective longitudinal studies and strategies are needed to investigate implications further and define the magnitude of the association between physical activity and periodontal disease.

No description available.

No description available.

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-09T13:37:10Z No. of bitstreams: 1 Jobson Filipe de Paula Cajueiro.pdf: 767324 bytes, checksum: 776ab3e5c28585de71b32d4d723d5483 (MD5) / Made available in DSpace on 2017-02-09T13:37:10Z (GMT). No. of bitstreams: 1 Jobson Filipe de Paula Cajueiro.pdf: 767324 bytes, checksum: 776ab3e5c28585de71b32d4d723d5483 (MD5) Previous issue date: 2014-02-07 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / Hypocalcemia in dairy cows has been studied around the world, mainly due to its impact on animal production and productivity, will be related to various diseases. However, few studies have been conducted on this disease in small ruminants, especially in dairy goats. Therefore , the aim of this study was to determine the concentrations of calcium during the transition period in dairy goats in order to differentiate groups of hypocalcemic animals (G1) and normal calcium (G2), in order to infer the influence of subclinical hypocalcemia in profile metabolic thereof. For this, 35 goats, otherwise healthy, pregnant, primiparous and multiparous, crossbred or purebred dairy breeds used. Blood samples were collected by jugular venipuncture before delivery [30 , 20 and 10 days before parturition (dap)] , on the day of partum and post -partum [10,20,30,40,50 and 60 days later parturition (dpp)]. The variables measured were: glucose, non-esterified fatty acids (NEFA), β - hydroxybutyrate (BHB), cholesterol, triglycerides, amylase, total protein (TP), albumin, urea, creatinine, aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), creatine kinase (CK), total calcium, phosphorus (P), magnesium (Mg), chlorides, hormones cortisol and insulin, as well as ions Ca++, Na+ and K+. Were considered to have subclinical hypocalcemia goats showed that Ca++≤ 0.72mmol/L. The statistical model used for analysis was ANOVA . In G1 concentrations of Ca++ remained below that of G2 and the biggest difference ( P < 0.001 ) occurred at parturition . The highest concentrations of NEFA were observed at birth in both groups, but were higher in G1 (P< 0.03) than the G2 at delivery and during the pre -partum. The BHB had a slight growth from beginning to 40dpp in both the G1 and G2 and there were no differences between them. The behavior of amylase was increased in antepartum reaching their highest values to 10dpp and remained stable postpartum in both groups, did not return to their initial values. A decrease in the values of triglycerides 20dap until 10dpp and differences (P<0.05) were found between the pre-and postpartum in both groups occurred. Cholesterol remained slight growth in postpartum, a little more evident in G2 than in G1, however these did not differ. Reduction in the concentration of insulin to 10dap in both groups, but in this G1 was greater (P˂0.001) that some times postpartum. The highest values of cortisol and glucose occurred at delivery and there were no differences between groups. The PT values were rising delivery to 30dpp not returning to baseline values in both G1 and G2. Albumin fell to 20dap and grew from birth up to 30dpp when returned to its initial value in both groups. The lower (P<0.05) values of total calcium is given at birth and the G1 was lower than G2 in almost the entire period. It is concluded that in subclinically goats hypocalcemic serum concentrations of Ca++ fall before the normocalcêmicas goats and remain lower throughout the transition period and that some variables of the metabolic profile as NEFA, glucose, insulin and total calcium are strongly influenced by the Ca++. Furthermore, the lower food intake by goats with subclinical hypocalcemia is one of the main factors affecting the metabolic profile and probably the productivity of these animals. However, other studies should be conducted to measure the effects of this disease in its subclinical form , the production rates and the emergence of other diseases in the transition period in dairy goats. / A hipocalcemia em vacas leiteiras tem sido objeto de estudos ao redor do mundo, principalmente em função de seu impacto na produção e produtividade animal, por estar relacionada á diversas enfermidades. Entretanto, poucos trabalhos sobre esta enfermidade foram realizados em pequenos ruminantes, sobretudo em cabras leiteiras. Portanto, o objetivo deste trabalho foi determinar as concentrações de cálcio durante o período de transição em cabras leiteiras, afim de, diferenciar grupos de animais hipocalcêmicos (G1) e normocalcêmicos (G2), com o objetivo de inferir a influência da hipocalcemia subclínica no perfil metabólico destes. Para tanto, 35 cabras, hígidas, gestantes, primíparas e multíparas, mestiças ou puras de raças leiteiras foram utilizadas. Amostras de sangue foram colhidas por venopunção jugular no pré-parto [30, 20 e 10 dias antes do parto (dap)], no dia do parto e no pós-parto [10, 20, 30, 40, 50 e 60 dias depois do parto (dpp)]. As variáveis mensuradas foram: glicose, ácidos graxos não esterificados (AGNE), β-hidroxibutirato (BHB), colesterol, triglicerídeos, amilase, proteínas totais (PT), albumina, uréia, creatinina, aspartato aminotransferase (AST), gama glutamiltransferase (GGT), creatina quinase (CK), cálcio total, fósforo (P), magnésio (Mg), cloretos, os hormônios cortisol e insulina, bem como os íons Ca++, Na+ e K+. Foram considerados com hipocalcemia subclínica as cabras que apresentaram Ca++≤0,72mmol/L. O modelo estatístico empregado para análise dos resultados foi a ANOVA. No G1 as concentrações de Ca++ mantiveram-se sempre abaixo do G2 e a maior diferença (P<0,001) ocorreu no dia do parto. As maiores concentrações de AGNE foram verificadas no parto, em ambos os grupos, porém no G1 foram maiores (P<0,03) que no G2 no parto e durante o pré-parto. O BHB teve um discreto crescimento do início até o 40dpp, tanto no G1 quanto no G2 e não houve diferenças entre eles. O comportamento da amilase foi crescente no pré-parto alcançando seus maiores valores aos 10dpp e manteve-se estável no pós-parto, em ambos os grupos, não retornando aos seus valores iniciais. Ocorreu uma queda nos valores dos triglicerídeos dos 20dap até os 10dpp e diferenças (P<0,05) foram verificadas entre o pré e o pós-parto, em ambos os grupos. O colesterol manteve discreto crescimento no pós parto, um pouco mais evidente no G2 que no G1, entretanto estes não diferiram. Houve redução na concentração da insulina aos 10dap em ambos os grupos, porém no G1 esta foi mais expressiva (P˂0,001) que alguns momentos do pós-parto. Os maiores valores do cortisol e da glicose ocorreram no parto e não ocorreram diferenças entre os grupos. Os valores de PT foram crescentes do parto aos 30dpp não retornando aos valores iniciais tanto no G1 quanto no G2. A albumina caiu aos 20dap e apresentou crescimento a partir do parto até aos 30dpp quando retornou ao seu valor inicial em ambos os grupos. Os menores (P<0,05) valores do cálcio total se deram no parto e o G1 foi menor que o G2 em quase todo o período. Conclui-se então que em cabras subclinicamente hipocalcêmicas as concentrações séricas do Ca++ caem antes que nas cabras normocalcêmicas e permanecem mais baixas durante todo o período de transição e que algumas variáveis do perfil metabólico como AGNE, glicose, insulina e o cálcio total sofrem forte influência do Ca++. Além disso, a menor ingestão alimentos pelas cabras com hipocalcemia subclínica é um dos principais fatores de interferência no perfil metabólico e provavelmente na produtividade destes animais. Contudo, outros trabalhos devem ser realizados a fim de mensurar os efeitos desta doença, na sua forma subclínica, nos índices produtivos e no surgimento de outras enfermidades no período de transição em cabras leiteiras.

Genome-wide associations studies (GWASs) have identified hundreds of loci that are strongly associated with coronary artery disease and its risk factors. However, the causal variants and genes remain unknown for the vast majority of the identified loci. Zebrafish model systems coupled with clustered regularly interspaced short palindromic repeats-C–associated 9 (CRISPR Cas-9) mutagenesis have enabled the possibility to systematically characterize candidate genes in GWAS-identified loci. In this thesis, canonical correlation analysis (CCA) was used to identify putative causal genes in multiplexed genetic screens for atherogenic traits in zebrafish larvae in an efficient manner. The two datasets used in this thesis contained genes and phenotypes obtained through sequencing and high-throughput imaging of fish larvae. Dataset 1 contained (7 genes, 11 phenotypes, n = 384) and dataset 2 (4 genes, 11 phenotypes, n = 384). CCA’s multiple genes vs. multiple phenotype analysis in dataset 1 identified the genes met, pepd, timd4 and vegfa to have an association with the total cholesterol, triglycerides, glucose, corrected lipid disposition, as well as co- localization of (macrophage and lipid deposition,) (neutrophils and lipid deposition) and (macrophage and neutrophils). In dataset 2, CCA found previously reported correlation of genes apobb1 and apoea with total cholesterol, low-density lipoprotein and triglycerides as well as co localization of neutrophils and lipids. In comparison with hierarchical linear model, CCA represents a powerful and promising tool to identify causal genes for cardiovascular diseases in data from zebrafish model systems.