As obesity and obesity-associated diseases become more prevalent in western societies, new methods to promote weight-loss and protect patients from the dangerous consequences of excess adipose tissue are needed. While both researchers and clinicians previously turned to chemical uncouplers for many decades to create a negative energy balance and thus promote weight-loss, these compounds proved to be extremely dangerous treatment options, even when taken in mild dosages. Substances like 2-4 dinitrophenol (DNP), were able to significantly induce weight loss, however many life-threatening conditions such as fatal hyperthermia are commonly attributed to these uncoupling agents. Recently, with the discovery of natural brown/beige fat reservoirs in humans, many members of the medical community have become heavily invested in the targeting of more localized, less systemic uncoupling tissues. The action of UCP-1 in human thermogenic adipose introduces an opportunity to harness a natural, yet futile cycle, and hence boost a patient’s basal metabolism without ultimately compromising their long-term health. Many challenges remain before such a treatment is viable, including deciphering the biochemical pathways that induce brown fat thermogenesis. It appears that several uncoupling signals may govern the genetic programs that lead to this thermogenic activity, and the "browning" of white adipose stores in humans. Particularly in the last ten years, many studies have uncovered new components of the thermogenic program by ablating target genes in mice. While a direct pathway of thermogenic activation does exist when subjects are placed in a cold environment, a successful, high-adoption, anti-obesity treatment through a thermogenic regimen will likely involve a gene-therapy or protein-based biopharmaceutical intervention. It is conceivable that thermogenic manipulation could play a significant role in the battle against obesity and obesity-associated diseases, however a significant intellectual breakthrough in appetite suppression and/or appetite management (i.e. a successful intervention of the orexigenic and anorexigenic physiological pathways) could in theory supplant this approach.

Introdução: É indiscutível a importância da alimentação adequada na manutenção do peso corporal e na saúde humana. Estudos epidemiológicos recentes mostram um elevado índice de obesidade e síndrome metabólica na população mundial. O consumo de alimentos termogênicos, dentre eles os capsinóides, tem demonstrado efeitos na redução de gordura corporal, melhora na tolerância à glicose, propriedades anti-inflamatórias, atividades antihiperlipidêmica e antioxidante. Objetivo: O objetivo do presente trabalho foi investigar o efeito termogênico dos capsinóides e sua influência na adiposidade corporal em ratos Wistar adultos. Métodos: Avaliou-se 24 animais e estes foram separados em quatro grupos: Padrão (P), Padrão + Capsinóides (PC), Dieta Hiperlipídica (H) e Dieta Hiperlipídica + Capsinóides (HC). Durante um período de 6 semanas os grupos PC e HC receberam suplementação diária, adicionada à dieta, de capsinóides na dosagem de 0,18mg/Kg de peso do animal. Durante o experimento foram avaliados o peso corporal semanalmente, a ingestão alimentar e calórica diária e, ao final do estudo, os animais foram sacrificados, sendo coletados sangue total e tecidos: hepático, adiposo epididimal, marrom e retroperitoneal. Foi realizada avaliação da glicemia inicial, final, triglicérides, colesterol e HDL-colesterol. Calculou-se ainda eficiência alimentar e energética além de HOMA-? e HOMA-IR. Todos os testes de hipóteses desenvolvidos nesse trabalho consideraram uma significância de 5%, ou seja, a hipótese nula foi rejeitada quando p-valor foi menor ou igual a 0,05. Foram feitas análises por ANOVA, ANOVA Two Way e Tukey. Resultados: Não observou-se diferença significativa com uso de capsinóides e também com a dieta hiperlipídica para ganho de peso, triglicérides, HDL-colesterol e colesterol sérico. O tecido adiposo marrom e o tecido adiposo epididimal apresentaram valores significativamente menores nos grupos suplementados com capsinóides (HC e PC). Os grupos que receberam dieta hiperlipídica (H+HC) tiveram a adiposidade corporal significativamente maior do que os grupos com dieta padrão (P+PC), porém quando suplementados com capsinóides, não apresentaram diferenças significativas na adiposidade corporal. A ingestão alimentar (g) e ingestão calórica nos grupos suplementados com capsinóides (PC+HC) foram significativamente maiores em relação aos grupos não suplementados (H+P), porém tiveram o mesmo ganho de peso, ou seja a dieta suplementada com capsinóides apresentou menor eficiência. Os grupos suplementados com capsinóides (PC+HC) apresentaram também menor diferença entre glicemia final menos a inicial em relação ao grupo não suplementado (H+P). Conclusão: Os capsinóides preveniram o ganho de peso corporal dos animais suplementados, pois tiveram significativamente maior consumo alimentar e calórico, porém ganharam peso similar aos não suplementados, e ainda o uso dos capsinóides não reduziram a adiposidade corporal significativamente. A importância de tais achados e a sua relação com o potencial efeito termogênico relacionado aos capsinóides precisam ser confirmados através de novos estudos. / Introduction: There is no doubt regarding the diet\'s role in weight maintenance and human health. Recent epidemiological studies show a high rate of obesity and metabolic syndrome in the world population. The consumption of thermogenic foods, among them capsinoids, has shown efficacy in reducing body fat, improved glucose tolerance, anti-inflammatory properties, antihyperlipidemic and antioxidant activities. Objective: The aim of this study was to investigate the thermogenic effect of capsinoids and its influence on body adiposity in adult Wistar rats. Methods: It was evaluated 24 animals and these were divided into four groups: Standard (P), standard + capsinoids (PC), high-fat diet (H) and high-fat diet + capsinoids (HC). Over a period of 6 weeks, the PC and HC groups received daily supplementation of capsinoids in dosage 0,18mg / kg of animal weight added to their diet. During the experiment weekly body weight, food intake and daily calorie were evaluated, and at the end of the study, the animals were sacrificed, being collected whole blood and tissues: liver, epididymal adipose, brown and retroperitoneal. It was conducted an evaluation of initial and final glycemia, triglycerides, cholesterol and HDL-cholesterol. It was also calculated feed and energy efficiency as well as HOMA-? and HOMA-IR. All statistical tests developed in this study considered a significance of 5%, i.e., the null hypothesis was rejected when p-value was less than or equal to 0.05. Analyses were performed by ANOVA, Two Way ANOVA and Tukey. Results: No significant difference was observed with the use of capsinoids and also with the high-fat diet to gain weight, triglycerides, HDL-cholesterol and serum cholesterol. The brown adipose tissue and the epididymal adipose tissue were significantly lower in the groups supplemented with capsinoids (HC and PC). The group that received high-fat diet (H + HC) had a significant higher body adiposity than with standard diet groups (P + PC), but when supplemented with capsinoids, no significant differences in body adiposity were presented. Food intake (g) and caloric intake in the groups supplemented with capsinoids (PC + HC) were significantly higher in the groups unsupplemented (H + P), but had the same weight gain, i.e., the diet supplemented with capsinoids presented lower efficiency. The groups supplemented with capsinoids (PC + HC) also had a lower difference between the final blood glucose less the initial compared to unsupplemented group (H + P). Conclusion: Capsinoids prevented the weight gain of supplemented animals, because they had significant higher food and calorie intake, but gained weight similar to the unsupplemented. Besides, the use of capsinoids did not significantly reduce body adiposity. The importance of these findings and their relationship with the potential thermogenic effect related to capsinoids need to be confirmed by further studies.

Carbon isotope analyses of gases extracted from drilling muds while drilling in the Western Canada Sedimentary Basin (WCSB) can be used to create carbon isotopic depth profiles. These profiles provide essentially continuous data through the stratigraphic section, offering a unique opportunity to study the in-situ gases in various rock matrices. Carbon isotope and molecular compositions of Jurassic - Cretaceous mud gases have been examined from ten depth profiles in the undisturbed WCSB. The isotopic profiles are surprisingly complex, showing numerous inflections and deviations towards increasing and decreasing carbon isotope values (13C) and wetness index with depth that suggest a correlation with the stratigraphic framework and can be explained in terms of the origin and alteration of the gases. However, the gas isotope geochemistry must be incorporated and applied in a multidisciplinary approach in order to gain a better understanding of causes of variations. The discernible degree of correlativity of carbon isotope trends between the WCSB wells are likely to be related to the presence of major gas compartments bounded by stratigraphic surfaces, compartmentalization of the gas being strongly influenced by stratigraphic variations. The majority of these boundaries act as effective barriers to gas migration. Mudgas geochemistry is best employed in conjunction with petrophysical analysis and conversion into mineralogy, for defining details of transition zones and reservoir compartments. Combined evidence suggests that isotopic variability of WCSB gases is only partly induced by source maturity at one single location. The main shifts of carbon isotope ratios are likely to be related to the physical properties of the rocks, differences between organic precursors (type II versus type III kerogen), total organic carbon (TOC) content, gas biodegradation and mixing. The present thesis demonstrates that the carbon isotopic mud gas profiles represent a powerful tool that provide information about the compartmentalization of the gas, the effectiveness of low permeability barriers, the origin, alteration and maturity of gases, and the regional gas dynamics. Mudgas geochemistry proves to be one part of the puzzle in the investigation of regional gas dynamics, and should be integrated with geological information, lithostratigraphic-, and sequence stratigraphic information, petrographic information and geophysical data.

This contribution aims to publicize the efforts made in the identification of gas hydrates in the Uruguayan continental shelf, analyze the most outstanding aspects related to its energy potential, as well as include this topic in other areas of knowledge for a comprehensive understanding of the subject. The hydrates, crystalline solid formed mainly by water and natural gas, are reservoirs of carbon that occur naturally in the continents in permafrost areas, and at sea, in the offshore basins of continental margins. They contain more than twice the total carbon in the world, surpassing the conventional hydrocarbon reserves. Principal energy programs foresee its commercial exploitation by 2015. International research programs include not only the energy aspect, but studying such systems considering their participation in the global carbon cycle, climate change and benthic communities associated with them. In our country, several seismic surveys showed evidence of the presence of gas hydrates in continental shelf and the surrounding area. The first survey was carried out by Brazil in the south of the Brazilian continental shelf, ANCAP then showed the continuity of the hydrate layer on the Uruguayan continental shelf and estimated the gas potential of the mineralized layer (87 TCF). Finally, the BGR survey verified the existence of seismic evidence of gas hydrates layer and the presence of free gas below these. The typical seismic response of gas hydrate and free gas is the BSR (Bottom Simulating Reflector) and is interpreted as a positive intensity reflection, followed by a negative intensity, showing the wave passage from a high acoustic impedance zone to a low acoustic impedance zone.

No description available.

Introdução: É indiscutível a importância da alimentação adequada na manutenção do peso corporal e na saúde humana. Estudos epidemiológicos recentes mostram um elevado índice de obesidade e síndrome metabólica na população mundial. O consumo de alimentos termogênicos, dentre eles os capsinóides, tem demonstrado efeitos na redução de gordura corporal, melhora na tolerância à glicose, propriedades anti-inflamatórias, atividades antihiperlipidêmica e antioxidante. Objetivo: O objetivo do presente trabalho foi investigar o efeito termogênico dos capsinóides e sua influência na adiposidade corporal em ratos Wistar adultos. Métodos: Avaliou-se 24 animais e estes foram separados em quatro grupos: Padrão (P), Padrão + Capsinóides (PC), Dieta Hiperlipídica (H) e Dieta Hiperlipídica + Capsinóides (HC). Durante um período de 6 semanas os grupos PC e HC receberam suplementação diária, adicionada à dieta, de capsinóides na dosagem de 0,18mg/Kg de peso do animal. Durante o experimento foram avaliados o peso corporal semanalmente, a ingestão alimentar e calórica diária e, ao final do estudo, os animais foram sacrificados, sendo coletados sangue total e tecidos: hepático, adiposo epididimal, marrom e retroperitoneal. Foi realizada avaliação da glicemia inicial, final, triglicérides, colesterol e HDL-colesterol. Calculou-se ainda eficiência alimentar e energética além de HOMA-? e HOMA-IR. Todos os testes de hipóteses desenvolvidos nesse trabalho consideraram uma significância de 5%, ou seja, a hipótese nula foi rejeitada quando p-valor foi menor ou igual a 0,05. Foram feitas análises por ANOVA, ANOVA Two Way e Tukey. Resultados: Não observou-se diferença significativa com uso de capsinóides e também com a dieta hiperlipídica para ganho de peso, triglicérides, HDL-colesterol e colesterol sérico. O tecido adiposo marrom e o tecido adiposo epididimal apresentaram valores significativamente menores nos grupos suplementados com capsinóides (HC e PC). Os grupos que receberam dieta hiperlipídica (H+HC) tiveram a adiposidade corporal significativamente maior do que os grupos com dieta padrão (P+PC), porém quando suplementados com capsinóides, não apresentaram diferenças significativas na adiposidade corporal. A ingestão alimentar (g) e ingestão calórica nos grupos suplementados com capsinóides (PC+HC) foram significativamente maiores em relação aos grupos não suplementados (H+P), porém tiveram o mesmo ganho de peso, ou seja a dieta suplementada com capsinóides apresentou menor eficiência. Os grupos suplementados com capsinóides (PC+HC) apresentaram também menor diferença entre glicemia final menos a inicial em relação ao grupo não suplementado (H+P). Conclusão: Os capsinóides preveniram o ganho de peso corporal dos animais suplementados, pois tiveram significativamente maior consumo alimentar e calórico, porém ganharam peso similar aos não suplementados, e ainda o uso dos capsinóides não reduziram a adiposidade corporal significativamente. A importância de tais achados e a sua relação com o potencial efeito termogênico relacionado aos capsinóides precisam ser confirmados através de novos estudos. / Introduction: There is no doubt regarding the diet\'s role in weight maintenance and human health. Recent epidemiological studies show a high rate of obesity and metabolic syndrome in the world population. The consumption of thermogenic foods, among them capsinoids, has shown efficacy in reducing body fat, improved glucose tolerance, anti-inflammatory properties, antihyperlipidemic and antioxidant activities. Objective: The aim of this study was to investigate the thermogenic effect of capsinoids and its influence on body adiposity in adult Wistar rats. Methods: It was evaluated 24 animals and these were divided into four groups: Standard (P), standard + capsinoids (PC), high-fat diet (H) and high-fat diet + capsinoids (HC). Over a period of 6 weeks, the PC and HC groups received daily supplementation of capsinoids in dosage 0,18mg / kg of animal weight added to their diet. During the experiment weekly body weight, food intake and daily calorie were evaluated, and at the end of the study, the animals were sacrificed, being collected whole blood and tissues: liver, epididymal adipose, brown and retroperitoneal. It was conducted an evaluation of initial and final glycemia, triglycerides, cholesterol and HDL-cholesterol. It was also calculated feed and energy efficiency as well as HOMA-? and HOMA-IR. All statistical tests developed in this study considered a significance of 5%, i.e., the null hypothesis was rejected when p-value was less than or equal to 0.05. Analyses were performed by ANOVA, Two Way ANOVA and Tukey. Results: No significant difference was observed with the use of capsinoids and also with the high-fat diet to gain weight, triglycerides, HDL-cholesterol and serum cholesterol. The brown adipose tissue and the epididymal adipose tissue were significantly lower in the groups supplemented with capsinoids (HC and PC). The group that received high-fat diet (H + HC) had a significant higher body adiposity than with standard diet groups (P + PC), but when supplemented with capsinoids, no significant differences in body adiposity were presented. Food intake (g) and caloric intake in the groups supplemented with capsinoids (PC + HC) were significantly higher in the groups unsupplemented (H + P), but had the same weight gain, i.e., the diet supplemented with capsinoids presented lower efficiency. The groups supplemented with capsinoids (PC + HC) also had a lower difference between the final blood glucose less the initial compared to unsupplemented group (H + P). Conclusion: Capsinoids prevented the weight gain of supplemented animals, because they had significant higher food and calorie intake, but gained weight similar to the unsupplemented. Besides, the use of capsinoids did not significantly reduce body adiposity. The importance of these findings and their relationship with the potential thermogenic effect related to capsinoids need to be confirmed by further studies.

hjlahgih / Thesis (DPhil (Human Movement Science))--University of Pretoria, 2005. / Biokinetics, Sport and Leisure Sciences / unrestricted

No description available.

PhD Dissertation / Obesity is a major risk factor for type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD), and is attributed to excess energy intake in comparison to energy expenditure. Therapeutics that reduce energy intake in obesity have limited efficacy, with weight loss typically reaching less than 10% of initial body mass, leading to efforts to uncover new therapies that may increase energy expenditure. Unlike lipid-storing white adipose tissue, brown and beige adipose tissues undergo futile cycling, oxidizing lipids and carbohydrates thereby increasing energy expenditure. With obesity, the metabolic activity of brown and beige adipose tissue is reduced, suggesting that restoring adipose tissue thermogenesis may represent a new means to enhance energy expenditure. Previous studies in mice have shown that peripheral serotonin synthesis by the enzyme tryptophan hydroxylase 1 (Tph1) inhibits adipose tissue thermogenesis and contributes to the development of obesity, insulin resistance and NAFLD. However, the primary Tph1 expressing tissue(s) inhibiting adipose tissue futile cycling is not known. In this thesis, we genetically removed Tph1 in mast cells of mice and discovered that this elevated beige adipose tissue activity protecting mice from developing high-fat diet induced obesity, insulin resistance and NAFLD. In contrast to these findings, genetic deletion of Tph1 in adipocytes did not result in protection from obesity, suggesting that mast cells are the primary source of serotonin that inhibits white adipose tissue thermogenesis. Lastly, to determine the importance of adipose tissue thermogenesis in mediating the beneficial metabolic effects of reduced Tph1, mice were housed at thermoneutrality, blocking the requirement for adipose tissue thermogenesis. Under these conditions, mice lacking Tph1 had comparable brown and beige adipose tissue metabolic activity, energy expenditure and adiposity, however, surprisingly, were still protected from insulin resistance and NAFLD. The studies in this dissertation have discovered that mast cell Tph1 is critical for inhibiting adipose tissue thermogenesis and that serotonin plays an important role in promoting NAFLD, independently of its inhibitory effects on adipose tissue thermogenesis. Collectively, these findings further define the roles of serotonin in regulating whole-body energy metabolism, providing critical clues and mechanistic insights for potential therapies to mitigate metabolic diseases. / Dissertation / Doctor of Philosophy (Medical Science) / Obesity, type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) can develop when caloric intake exceeds expenditure. In contrast to lipid-storing white fat, brown and beige fat burn calories. Serotonin is a hormone that reduces the burning of calories in fat, therefore finding ways to inhibit its effects on fat tissue without altering serotonin in the brain may lead to new therapies for obesity and other related diseases. In this thesis, we examined potential sources of serotonin that might inhibit the burning of calories in adipose tissue of mice. By reducing the synthesis of serotonin in a white blood cell called mast cells, but not fat cells, mice were protected from obesity, pre-diabetes and NAFLD due to increased activity of beige fat. Moreover, when we kept mice in a warm environment, thus reducing the need for mice to burn calories in brown and beige fat, this eliminated the effects of serotonin to promote obesity, but not pre-diabetes and NAFLD. These studies have identified how serotonin generated from mast cells inhibits the burning of calories in adipose tissue, a finding that may lead to new therapies for obesity, T2D and NAFLD.

The strong advertising appeal, the search for a good physique, and the improvement in physical performance, has risen the popularity of food supplements and other therapies with slimming supplements based on plant extracts. Since the law exempts food supplements from registration, they are easy targets for importation, commercialization e consumption by the population, which worsens malpractice cases of adulterations. Thus, the objectives of the present work were: research the presence of stimulants in food supplements for both slimming and weight gain; study the addition of synthetic caffeine in natural products based on plants used for weight loss; develop chromatographic methods using HPLC with photodiode detection to detect caffeine, salicin, ephedrine, hordenine, tyramine, octopamine and synephrine (including the L and D enantiomers). The stimulants were separated by reverse phase chromatography using octadecylsilane columns (C18). For L and D synephrine, chromatography with chiral phase of β-cyclodextrin was used. Detection limits varied from 0.02 mg L-1 to 0.35 mg L-1, while quantification limits ranged from 0.07 mg L-1 to 1.16 mg L-1 for the separation of stimulants in food supplements. For analyses of caffeine in herbal products, the LOD and LOQ were 0.048 mg L-1 and 0.16 mg L-1, respectively. For the anlysis of the enantiomers of p-synephrine, the L enantiomer presented a detection limit of 0.11 mg L-1 and quantification limit of 0.36 mg L-1, while the D enantiomer exhibited a detection limit of 0.41 mg L-1 and a quantification limit of 1.36 mg L-1. Each method developed was then applied to the sample, which were, dietary supplement samples (n = 47), herbal products (n = 100), and fruits of Citrus aurantium. Caffeine was the most frequent of the studied stimulants, often exceeding the labeled content and the maximum dose per day recommended (420 mg). The food supplements presented caffeine, synephrine and ephedrine as main stimulants in 53% of the studied samples. / O forte apelo do mercado publicitário, aliado à busca por um corpo padrão e à melhora no desempenho físico faz com que a popularidade dos suplementos alimentares e a associação destes com outras terapias envolvendo compostos emagrecedores a base de plantas seja cada vez maior. A lei que isenta de registro os suplementos alimentares, os torna alvo de fácil importação, comercialização e consumo pela população em geral, agravando ainda a prática de adulteração sobre os mesmos. Logo, este trabalho teve como objetivos: pesquisar a presença de estimulantes em suplementos alimentares para fins de emagrecimento, estudar a incidência de cafeína sintética adicionada em produtos naturais à base de plantas utilizadas para perda de peso; desenvolver métodos cromatográficos emplregando HPLC com detecção com arranjo de fotodiodos (DAD) para a determinação de cafeína, salicina, efedrina, hordenina, tiramina, octopamina e sinefrina (incluindo seus enantiômeros L e D). Os estimulantes foram separados por cromatografia de fase reversa em colunas de octadecilsilano (C18) e os enantiômeros por cromatografia de par iônico com fase quiral de β ciclodextrina. Os limites de detecção (LD) variaram de 0,02 mg L-1 a 0,35 mg L-1, já os limites de quantificação (LQ) ficaram na faixa de 0,07 mg L-1 e 1,16 mg L-1 na separação dos estimulantes em suplementos alimentares. Para as análises de cafeína em produtos naturais a base de plantas, os LD e LQ foram 0,048 mg L-1 e 0,16 mg L-1 respectivamente. Para os enantiômeros da p-sinefrina, o enantiômero L apresentou LD de 0,11 mg L-1 e LQ de 0,36 mg L-1, já o enantiômero D exibiu um LD de 0,41 mg L-1 e LQ de 1,36 mg L-1. Cada método desenvolvido foi posteriormente aplicado em amostras de suplementos alimentares (n=47), produtos naturais à base de plantas (n=100) e fruto de Citrus aurantium. Dos compostos estudados, a cafeína foi a que se apresentou mais frequente, muitas vezes excedendo os teores rotulados nos produtos, ou então a dose máxima recomendada por dia (420 mg). Já os suplementos alimentares apresentaram cafeína, sinefrina e efedrina como principais estimulantes em 53% das amostras estudadas.