vii, 203 leaves : tables, graphs ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.1980) from the Dept. of Obstetrics and Gynaecology, University of Adelaide

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph.D.)--Medical University of Ohio, 2004. / "In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Medical Sciences." Major advisor: Sonia M. Najjar. Includes abstract. Document formatted into pages: v, 217 p. Title from title page of PDF document. Bibliography: pages 158-216.

Thesis (Ph.D. in Microbiology) -- University of Colorado, 2006. / Typescript. Includes bibliographical references (leaves 145-167). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Dissertation (Ph.D.) -- University of Texas Southwestern Medical Center at Dallas, 2006. / Vita. Bibliography: pp.107-116

Introdução Os feijões comuns, da espécie Phaseolus vulgaris, são amplamente produzidos e consumidos no Brasil. As variedades, carioca e preto ganham destaque na região Sudeste do país. Encontra-se descrita na literatura a ação hipocolesterolemizante de algumas leguminosas, tais como, soja, tremoço e feijão caupi, que podem estar associados à redução do risco de doenças cardiovasculares. Objetivo Avaliar o potencial efeito da adição de farinhas de feijões carioca e preto (Phaseolus vulgaris) no metabolismo lipídico de hamsters alimentados com dieta contendo gordura saturada e colesterol. Métodos A produção das farinhas dos feijões envolveu as etapas de autoclavagem, congelamento, liofilização e moagem. As propriedades hipocolesterolemizantes destas farinhas foram avaliadas por meio de dois ensaios biológicos. Foram utilizados hamsters Golden Syrian, machos com 21 dias, pesando 60 ± 4g, que receberam as dietas experimentais ad libitum. No Ensaio A, os animais foram separados em 3 grupos, diferenciados pela dieta. Todas as dietas eram hipercolesterolemizantes [13.5 por cento de gordura de coco e 0.1 por cento colesterol] e tinham as mesmas quantidades de proteínas, carboidratos, fibras, vitaminas e minerais. O Grupo Controle (C) tinha como fonte protéica a caseína; no Grupo Feijão Carioca (FC) a farinha de feijão carioca representou 15 por cento do peso total da dieta e no Grupo Feijão Preto a farinha de feijão preto representou 15 por cento do peso total da dieta. No Ensaio B, os animais foram separados em três grupos novamente. Desta vez, a única diferença entre os grupos foi quanto a fonte protéica, para o grupo controle (C) somente caseína, para o grupo feijão carioca (FC), 67 por cento de feijão e 7,5 por cento de caseína e para o grupo feijão preto (FP), 62 por cento de feijão e 7,5 por cento de caseína. Nos dois ensaios, após 21 dias de experimento, foi realizada coleta de materiais biológicos (plasma, fígado e fezes). Resultados O processo de produção das farinhas de feijões cozidas liofilizadas não alterou a composição centesimal das matérias-primas. A análise de fibras alimentares revelou que não há diferenças entre os cultivares Pérola e Uirapuru. No Ensaio A, as concentrações de colesterol não HDL e HDL colesterol foram maiores nos grupos que receberam feijão de maneira significativa. Quanto aos demais parâmetros plasmáticos não foram observadas diferenças entre os grupos. No Ensaio B as concentrações plasmáticas de triglicerídeos foram maiores no grupo FP. As concentrações de HDL colesterol foram maiores nos grupos FP e FC, sendo estatisticamente significativa para o feijão carioca em relação ao grupo controle. As excreções fecais de ácidos biliares foram maiores no grupo FC e a de colesterol no grupo C. A determinação de lipídeos totais no fígado não revelou diferenças entre os grupos, dados que corroboraram com a análise do grau de esteatose nos fígados, a qual demonstrou desenvolvimento de acúmulo de lipídeos nos hepatócitos dos animais dos três grupos. O teste qui quadrado mostrou que as variáveis grau de esteatose e tipo de dieta, assim como tipo de dieta e grau de inflamação portal hepática são independentes. Já o grau de inflamação parenquimatosa hepática está associado ao tipo de dieta e o feijão carioca mostrou-se capaz de reduzir em 30 por cento o risco de desenvolver esteatoepatite severa. Conclusões Os feijões não foram capazes de proteger contra o aumento do colesterol total, triglicérides e colesterol não HDL no plasma, mas mesmo na presença de gordura saturada e colesterol na dieta, o feijão carioca foi capaz de aumentar a HDL, mostrando que o mecanismo de remoção do colesterol plasmático foi preservado. O feijão carioca mostrou-se eficaz na proteção contra a inflamação parenquimatosa hepática severa. / Carioca and black beans are the varieties of Phaseolus vulgaris most consumed on Brazil Southwest. It is well described that some legumes, as soy and cowpea beans, have hypocholesterolaemic effects. To test cholesterol-lowering properties of carioca and black beans, two biological assays were conducted. Golden Syrian hamsters, 21 days old, were housed individually under 12 h light-dark cycle and temperature-controlled environment, with free access to food and water. There was a adaptation period of 6 days, before the start of experimental period. In Assay A, the animals (n=19) were randomly assigned to three distinct groups. All groups received a hypercholesterolaemic diet (13.5 per cent coconut oil and 0.1 per cent cholesterol) and similar amounts of proteins, carbohydrates, fiber, vitamins and minerals to suit the animal requirements. Control group received casein as the only protein source; Carioca bean group received 15 per cent of carioca bean flour and casein to complement protein requirement and Black bean group received 15 per cent of black bean flour and casein to complement protein requirement. After 21 days, the experimental period was over and liver, blood and feces were collected. In Assay B, all groups also received a hypercholesterolaemic diet (13.5 per cent coconut oil and 0.1 per cent cholesterol). In this assay the only difference between groups (n=27) was protein source: casein for control group, and the others received carioca (67 per cent ) or black bean whole seed flour (62 per cent ) plus 7,5 per cent of casein. The beans flours obtained showed no differences in chemical composition. In Assay A, plasma HDL cholesterol and non-HDL cholesterol were higher in Carioca bean group and Black bean group. The other plasma parameters had no differences. In assay B, plasma triglyceride was higher in Black bean group. The HDL cholesterol was increased in both beans groups, and was significant in Carioca group. Fecal excretion of bile acids was higher in animals of Carioca bean group. Fecal excretion of cholesterol was higher in Control group. There were no differences between groups in total liver lipid concentration, data supporting the steatosis analysis in livers. The chi-square test showed that the type of experimental diet and steatosis grade were independents, also the portal hepatic inflammation was not associated with the experimental diets. The parenchymal inflammation of the liver was associated with Carioca bean group, which showed that the chance of developing severe inflammation was 30 per cent lower in carioca bean group compared with Control group. Beans had no cholesterol-lowering effect, but the HDL increases in plasma and lower inflammation in Carioca bean group deserves further investigation.

Heat exposure causes several physiological and metabolic alterations. Although lipids are vital in sustaining energy production, heat-induced alterations in lipid metabolism have not been clearly established. CHAPTER 1 reviews the known metabolic alterations resulting from heat stress, with a specific focus on changes in whole-body lipid utilization and plasma lipids. CHAPTER 1also outlines the physiological changes caused by heat stress, and their role in reducing exercise performance. The study presented in CHAPTER 2 has shown that, compared to thermoneutral conditions, NEFA concentrations were 37% higher following passive heating and 34% higher following exercise in the heat, without significant changes in whole-body lipid utilization. In addition, the level of hyperthermia attained during passive pre-heating and exercise in the heat resulted in a 13% decrease in total external work and a significantly higher rate of perceived exertion. CHAPTER 3 summarizes the study results and presents the limitations and applications of the study.

Adipose tissue plays a central role in the regulation of lipid storage and mobilization. A tight control between adipose tissue lipid storage and mobilization functions must be exerted to prevent an overload of lipids at other organs such as the heart, liver and skeletal muscles, and favor the risk of developing metabolic disorders, such as Type 2 diabetes and cardiovascular diseases (CVD). There is strong evidence from animal studies that low oxygen levels (hypoxia) are noted in adipose tissue as the mass of the organ excessively expands and, in turn, exacerbates some adipose tissue functions. Whether hypoxia exposure, which could be derived from reduced environmental oxygen availability, disease or a combination of both, affects adipose tissue lipid storage and mobilization functions in humans is not well known. Using in vitro and in vivo approaches, this thesis aimed at characterizing the effects of hypoxia on human adipose tissue lipid storage and lipid mobilization functions. Study I investigated how hypoxia can modulate human adipose functions such as lipid storage and lipid mobilization in vitro. Study II examined whether acute intermittent hypoxia, which simulates obstructive sleep apnea, affects adipose tissue lipid storage/mobilization functions and triglyceride levels in healthy young men in postprandial state. Study III tested the effect of an acute 6-hour continuous exposure to hypoxia (fraction of inspired oxygen (FIO2) = 0.12)) on plasma triglyceride levels in healthy young men in the fasting state. Study I indicates that both acute (24h) and chronic (14d) hypoxia (3%, and 10% O2) modulate human adipose tissue lipid storage and mobilization functions in a different manner. Study II demonstrates that acute exposure to intermittent hypoxia (6h) is sufficient to increase plasma non-esterified fatty acids (NEFA) levels, as well as insulin levels, but does not alter circulating triglyceride or subcutaneous adipose tissue lipid storage and/or mobilization capacity ex vivo in healthy men. Study III shows that acute exposure to normobaric hypoxia increases circulating NEFA and glycerol concentrations but did not translate in altering circulating triglycerides in fasting healthy men. In conclusion, our observations suggest that an exposure to reduced oxygen levels impairs human adipose tissue storage and/or mobilization functions, a phenomenon known in the development of metabolic disorders, such as Type 2 diabetes and CVD.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21959号 / 医博第4501号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 横出 正之, 教授 小杉 眞司, 教授 長船 健二 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21993号 / 医博第4507号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長船 健二, 教授 竹内 理, 教授 横出 正之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM