非傳染性疾病是目前全球最常見的疾病之一。不健康的食相信是導致非傳染性疾病增加的主要因素之一。因此，我們就食對乳腺癌的形成和膽固醇代謝調控的影響進行了研究。 / 在去除卵巢的祼鼠模型中，我們研究了長期和短期熱量限制對乳腺癌腫瘤增殖的影響。14週齡的小鼠被隨機分為5組：自由攝食組 (AL)；熱量攝入控制在AL80% 的20%CCR組；熱量攝入控制在AL的70% 的30%CCR組；熱量攝入控制在AL的65% 的35%CCR組和短期熱量限制 （SCR）組 (前3.5週熱量攝入控制在AL的65%，之後的13.5週自由攝食)。10週後，熱量限制組的腫瘤體積明顯較AL組小 (P < 0.05)。排除攝食對體重的影響，SCR組的腫瘤重量明顯較AL組小 (P < 0.05)。本實驗結果表明，在此動物模型中，短期熱量限制能有效抑制乳腺癌細胞的增殖。 / 此外，我們還研究了芹菜素在肝細胞中對膽固醇代謝的影響。芹菜素是一種常見的黃酮類化合物。研究發現，在WRL-68細胞中，芹菜素能夠劑量依賴性的抑制3 - 羥基-3 - 甲基 - 戊二酸單酰輔酶還原酶 (HMGCR)和固醇調節元件結合蛋白-2 (SREBP-2) 信使RNA和蛋白的表達及其啟動子的轉錄活性。綜上所述，在肝細胞中，芹菜素能有效抑制HMGCR和SREBP-2的表達，從而達到降低膽固醇的效果。 / 總括而言，本研究表明在去除卵巢的祼鼠模型中，短期熱量限制能有效抑制乳腺癌細胞的生長和芹菜素能有效抑制HMGCR和SREBP-2的表達。 / Non-communicable diseases (NCD) are one of the leading causes of mortality in the developed and under-developing countries. Diet is a major risk factor of NCD. In the present study, effects of diet modification on breast cancer development and cholesterol metabolism were investigated. / In the first part of this study, the effect of chronic and short-term calorie restriction (CR) on breast tumor growth in ovariectomized nude mice was investigated. The calorie-restricted dietary regimen limited the total fat intake only. 14 week-old ovariectomized female nude mice were randomly assigned to ad libitum fed (AL), 20%CCR (17-week 80% of AL), 30%CCR (17-week 70% of AL), 35%CCR (17-week 65% of AL) and short-term CR (3.5-week 65% of AL followed by 13.5-week 100% AL consumption) groups. Starting from 10 weeks after transplant of cells, the tumor volumes in all calorie-restricted groups were significantly smaller (P < 0.05) than that in ad libitum control. At sacrifice, the tumor weight in short-term CR was significantly smaller (P < 0.05) than that in ad-libitum control after normalized with body weight. This indicated that short-term CR could suppress tumor in this model. / In the second part of this study, the effect of apigenin on cholesterol metabolism was investigated. Apigenin is one of the most abundant flavonoids. In the present study, we investigated the effect of apigenin on several cholesterol-related gene expression in hepatic cells. In WRL-68 cells treated with apigenin, promoter transcription activity, mRNA and protein expression of HMGCR and SREBP-2 were significantly decreased in a dose-dependent manner. Taken together, we concluded that apigenin inhibited HMGCR and SREBP-2 gene expressions in hepatic cells, which might elicit the hypocholesterolemic effects. / In conclusion, our study has demonstrated that short-term CR could significantly block the breast tumor growth in a mice model and apigenin could inhibit the expression of HMGCR and SREBP-2 in liver cell lines. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Wong, Tsz Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 83-99). / Abstracts also in Chinese. / ACKNOWLEGEMENTS --- p.i / ABSTRACT --- p.ii / 摘要 --- p.iv / list of abbreviations --- p.v / list of figures --- p.vii / list of tables --- p.IX / TABLE of CONTENTS --- p.X / Chapter 1 --- CHAPTER 1 --- p.1 / General Introduction --- p.1 / Chapter 1.1 --- Calorie Restriction and the Prevention of Postmenopausal Breast Cancer --- p.2 / Chapter 1.1.1 --- Breast Cancer --- p.2 / Chapter 1.1.2 --- Epidemiology of Excess Body Weight and Cancer Risk --- p.3 / Chapter 1.1.3 --- Calorie Restriction and Cancer Prevention --- p.7 / Chapter 1.1.4 --- Mechanistic Targets of Calorie Restriction --- p.8 / Chapter 1.1.4.1 --- Effect of Calorie Restriction on Estrogen --- p.8 / Chapter 1.1.4.1 --- Effect of Calorie Restriction on Cell Cycle Regulation --- p.12 / Chapter 1.1.4.1 --- Effect of Calorie Restriction on Apoptosis --- p.14 / Chapter 1.2 --- Effect of Apigenin on Cholesterol Homeostasis --- p.17 / Chapter 1.2.1 --- Cardiovascular Disease and Blood Cholesterol --- p.17 / Chapter 1.2.2 --- Molecular Regulation of Cholesterol Metabolism --- p.21 / Chapter 1.2.2.1 --- HMG-CoA Reductase --- p.21 / Chapter 1.2.2.2 --- CYP7A1 --- p.24 / Chapter 1.2.2.3 --- Apolipoprotein A-1 --- p.26 / Chapter 1.2.2.4 --- Low Density Lipoprotein Receptor --- p.29 / Chapter 1.2.2.5 --- Sterol Regulatory Element Binding Proteins --- p.31 / Chapter 1.2.3 --- Flavonoid and its Association with Cholesterol Metabolism --- p.36 / Chapter 1.2.4 --- Apigenin: A Potential Alternative --- p.39 / Chapter 2 --- CHAPTER 2 --- p.41 / MATERIALS AND METHODS --- p.41 / Chapter 2.1 --- Chemicals and Materials --- p.41 / Chapter 2.1.1 --- Chemicals --- p.41 / Chapter 2.1.2 --- Plasmids --- p.41 / Chapter 2.2 --- Cell Culture --- p.41 / Chapter 2.2.1 --- Maintainance of Cells --- p.41 / Chapter 2.2.2 --- Preparation of Cell Stock --- p.42 / Chapter 2.2.3 --- Cell Recovery from Liquid Nitrogen Stock --- p.42 / Chapter 2.3 --- Measurement of Cell viability --- p.43 / Chapter 2.4 --- Semi-Quantitative and Quantitative RT-PCR Assay --- p.43 / Chapter 2.4.1 --- RNA Isolation and cDNA Synthesis --- p.43 / Chapter 2.4.2 --- Quantitative Real Time PCR Assay --- p.43 / Chapter 2.4.2.1 --- Real Time PCR Using TaqMan Probe --- p.43 / Chapter 2.4.2.2 --- Real Time PCR Using SYBR Green Dye --- p.44 / Chapter 2.4.2.3 --- Statistical Analysis of 2⁻ΔΔ{U+A7F0}{U+1D40} Comparative Gene Expression --- p.44 / Chapter 2.5 --- Western Blot Analysis --- p.46 / Chapter 2.6 --- Measurement of Promoter Activity --- p.46 / Chapter 2.6.1 --- Plasmid Preparation --- p.46 / Chapter 2.6.2 --- Transient Transfection and Dual-Luciferase Assay --- p.47 / Chapter 2.7 --- Animal Experiment Design --- p.47 / Chapter 2.7.1 --- Animal Model and Dietary Regimens --- p.47 / Chapter 2.7.2 --- Tissue Sample Collection --- p.50 / Chapter 2.7.3 --- Plasma Estradiol Determination --- p.50 / Chapter 2.7.4 --- Protein and RNA extraction --- p.50 / Chapter 2.8 --- Statistical Analysis --- p.50 / Chapter 3 --- Chapter 3 --- p.51 / EFFECT OF CHRONIC AND short-term calorie restriction on breast tumor growth in ovariectomized nude mice --- p.51 / Chapter 3.1 --- Introduction --- p.51 / Chapter 3.2 --- Objectives --- p.52 / Chapter 3.3 --- Results --- p.53 / Chapter 3.3.1 --- Food Intakes, Body, Liver and Uterus Wet Weights of the Mice --- p.53 / Chapter 3.3.2 --- Tumor Development --- p.57 / Chapter 3.3.3 --- Plasma Estradiol Level --- p.62 / Chapter 3.3.4 --- Estradiol Responsive Gene expression in Tumors --- p.63 / Chapter 3.3.5 --- Cell Apoptotic and Cell Cycle-Regulated Protein expression in Tumors --- p.65 / Chapter 3.4 --- Discussion --- p.67 / Chapter 4 --- CHAPTER 4 --- p.69 / Apigenin inhibits the expression of hmg-coa reductase and srebp-2 in hepatic cells --- p.69 / Chapter 4.1 --- Introduction --- p.69 / Chapter 4.2 --- Objectives --- p.70 / Chapter 4.3 --- Results --- p.70 / Chapter 4.3.1 --- Effect of Apigenin on Cell Viability --- p.70 / Chapter 4.3.2 --- Effect of Apigenin on HMGCR, CYP7A1, LDLR, ApoA-1, SREBP-1 and SREBP-2 mRNA expressions --- p.72 / Chapter 4.3.3 --- Effect of Apigenin on HMGCR, LDLR, ApoA-1 and SREBP-2 Promoter Transcription Activity --- p.75 / Chapter 4.3.4 --- Effect of Apigenin on HMGCR, SREBP-1 and SREBP-2 Protein Expression --- p.77 / Chapter 4.3.5 --- Role of Estrogen Receptor in Apigenin induced SREBP-2 Inhibition --- p.79 / Chapter 4.4 --- Discussion --- p.80 / Chapter 5 --- CHAPTER 5 --- p.82 / SUMMARY --- p.82 / References --- p.83

Obesity is a disease of major proportion in the United States. The Surgeon General has identified obesity as a national health problem that affects approximately 34 million Americans. The aim of this study was to investigate the very-low-calorie diet, Optifast 70. Measurements for resting energy expenditure (REE} and body composition via circumference measurements (CBF} and infrared photospectromerty (NIR} with a Futrex 5000 were collected at weeks 1, 7, 13, 19, and 25. Biochemical data, including serum chemistry panel (SMA-12} and complete blood count (CBC}, were collected on weeks 1, 5, 9, 13, 17, 21, and 25. Lipid profiles were drawn on weeks 1 and 25. Participants ranged in age from 27 to 64. Subjects' mean body mass loss was -20.4 kg ± 6.6 kg with a maximum body mass loss of -33.23 kg and minimum body mass loss of -9.770 kg. Mean loss in body fat mass using infrared photospectrometry as a measurement was -13.4 kg; mean loss of lean body mass was -4.2 kg. A significant change was noted in resting energy expenditure over the course of the diet, and a positive correlation was identified between loss of body mass and resting energy expenditure. No significant correlation was identified between the loss of lean body mass or body fat mass and its relationship to resting energy expenditure. Both circumference and infrared body fat measurements showed a positive correlation as the loss in body mass increased, making their reliability better as subjects approached desirable weight. In examining biochemical data, only cholesterol showed a significant change over the course of the diet; all other parameters remained within normal limits. Variations in patients' lipid profiles were identified, but no significant changes were noted.

Thesis (M.S.)--University of Alabama at Birmingham, 2008. / Title from PDF of title page (viewed July 10, 2009). Includes bibliographical references (p. 32-39).

Mudanças no hábito alimentar têm sido descritas como prováveis causas da obesidade. Estudos mostram que o peso depende do balanço energético definido pela relação entre a energia ingerida e o gasto energético. Sugere-se que o padrão alimentar, levando em consideração a freqüência de refeições e sua distribuição durante o dia, possa estar relacionado com a obesidade. Um efetivo programa de perda de peso tem como objetivo a perda do excesso da gordura corporal e a manutenção da massa livre de gordura apropriada para manutenção da saúde. O cortisol é um dos principais hormônios secretados pelo córtex supra-renal com ação predominante no metabolismo intermediário, incluindo a regulação das proteínas, carboidratos, lipídeos e ácidos nucléicos.O presente estudo teve como objetivos determinar se a ingestão alimentar hipocalórica em pacientes obesas grau III, feita exclusivamente no período das 9:00 às 11:00 h em contraposição à mesma dieta oferecida das 18:00 às 20:00 h, é capaz de alterar a perda de peso, a composição corporal, o ritmo de cortisol, o gasto energético e o balanço nitrogenado. As pacientes foram internadas na Unidade Metabólica da Divisão de Nutrologia do Departamento de Clínica Médica do Hospital das Clínicas de Ribeirão Preto USP durante um período de 64 dias, sendo divididos em 3 internações de 18 dias. Na 1ª fase receberam dieta fracionada em 5 refeições /dia, considerada controle. Na 2ª fase, receberam a mesma dieta, no período das 9:00 às 11:00 h. E na 3ª fase receberam, também, a mesma dieta no período das 18:00 às 20:00 h. Entre uma internação e outra, as pacientes tiveram alta hospitalar por 5 dias, recebendo dieta domiciliar usual. Durante cada fase realizou-se dosagem de nitrogênio urinário e de cortisol salivar. Além disto, as pacientes foram submetidas à avaliação nutricional incluindo: antropometria, bioimpedância e calorimetria indireta. O cortisol salivar obedeceu ao mesmo ritmo nas 3 fases, tanto no 1º quanto no 18º dias de internação, apresentando o pico máximo às 8:00 h, diminuindo progressivamente até atingir o nadir às 21:00 h. Não houve alteração no ritmo do cortisol quando se alterou o horário da alimentação. Houve uma diminuição significativa (p< 0,05) para todos os parâmetros antropométricos, exceto para o índice cintura/quadril durante as três fases, não havendo diferença entre as 3 fases. Houve, nas 3 internações, uma diminuição significativa tanto na quantidade de nitrogênio ingerido quanto na quantidade de nitrogênio excretado a partir do 4º dia de internação. No 10º dia de internação, o balanço nitrogenado estava negativo nas 3 fases da dieta. Não houve diferença entre as fases para ingestão, excreção ou balanço nitrogenado. Mudanças no padrão do horário da ingestão alimentar por períodos de 18 dias não foram estímulo suficiente para provocar diferentes alterações de peso, da composição corporal, da ritmicidade e níveis de produção de cortisol, da taxa metabólica de repouso e balanço nitrogenado em mulheres grau III. / Changes in dietary habits have been implicated as potential causes of obesity. Studies have suggested that weight depends on the energetic balance, which is the relation between energy intake and energy expenditure. Dietary behavior, specially eating frequency and temporal distribution of eating events during the day, may be related to obesity. An effective weight loss program should reduce body fat and preserve lean body mass. Cortisol is an important corticosteroid produced by the adrenal. It exerts metabolic effects on intermediary metabolism, regulating protein, carbohydrates, lipids and nucleic acids metabolism. The present studys goals were: compare differences in weight loss, body composition, energy expenditure and nitrogen balance using hypo caloric diet offered in two different time intervals, first from 9:00 to 11:00, second from 18:00 to 20:00; determinate if there is difference on urinary nitrogen when food is offered on different time intervals, comparing with salivary cortisol levels, and show salivary cortisol secretion rhythm of obese females undergoing hypo caloric diet in different day times. The patients were under hospital regimen in the Metabolic Unit of the Nutrology Division of the Internal Medicine Department of the HCFMRP USP for a 64 days period, divided in 3 periods of 18 days each. On phase 1, the patients received food five times a day. On phase 2, they received the same diet, but the meals were between 09:00 and 11:00. On phase 3, the same diet was offered between 18:00 and 20:00. After each 18 day period, patients went home for a 5 day wash-out period, eating their regular home food and respecting their usual dietary behavior. On each phase urinary nitrogen and salivary cortisol were measured. Also a nutritional evaluation, including anthropometry, bioimpedance and indirect calorimetry were done. There were a reduction (p< 0,05) in all parameters, except the Waist/ Hip Ratio during all phases, but there were no difference between the phases. On the 3 phases there were a reduction on both, nitrogen intake and excretion. After the 10th in hospital day, nitrogen balance was negative on the 3 phases. There are no differences on nitrogen intake, excretion or balance between the 3 phases of food intake. Salivary cortisol followed the same rhythm on all 3 phases, both on the 1st and on the 18th in hospital days, having the peak salivary level at 08:00 h and the nadir level at 21:00 h. Changing meal times for 18 days did not change salivary cortisol circadian rhythm and did not promote changes in weight loss, body composition and rest energy expenditure in grade III obese females.

A obesidade é considerada uma doença multifatorial e pode envolver, em sua gênese, aspectos genéticos, metabólicos, ambientais, psicológicos e socioeconômicos. O crescimento expressivo da incidência mundial da obesidade desencadeia o surgimento contínuo de novas pesquisas em relação a esse tema e, nesse contexto, estudos recentes sugerem que a microbiota intestinal é um fator que pode contribuir com o desenvolvimento desta doença. Assim, existe a premissa que a alteração da composição da microbiota intestinal pode ser influenciada pelo estado nutricional (obesidade x eutrofia) e pela qualidade da alimentação. O presente estudo teve como objetivos: i. comparar a proporção dos filos predominantes da microbiota intestinal Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia e a razão Firmicutes/Bacteroidetes entre mulheres com obesidade grau III e mulheres eutróficas, e ii. investigar o impacto de uma dieta hipocalórica para perda de peso na composição da microbiota intestinal. Estudo prospectivo longitudinal, no qual foram selecionadas 20 mulheres com média de idade 33±3,1 anos, as quais foram divididas em dois grupos: Grupo Intervenção (GI): 10 mulheres com obesidade grau III (Índice de Massa Corporal (IMC) >40 kg/m2) que foram submetidas à intervenção nutricional (dieta hipocalórica) durante 8 semanas e Grupo Controle (GC):10 mulheres eutróficas (IMC entre 18,5 a 24,9 kg/m2). No GI, as coletas foram realizadas antes e após oito semanas da intervenção (GI) e, no GC em um único momento. Em cada momento, foram aferidos o peso e estatura; realizado o cálculo do IMC, análise composição corporal, taxa metabólica de repouso, consumo alimentar, glicemia e lipidograma, e coleta de amostra fecal. A análise da composição da microbiota intestinal em relação à abundância relativa dos Filos foi realizada por reação em cadeia da polimerase em tempo real (qPCR). Após oito semanas de dieta hipocalórica, houve redução do peso (119,5±10,3 para 114,9±10,2 kg), IMC (43,6±2,4 para 41,9±2,6 kg/m2), massa corporal gorda (MG) (62,4±7,5 para 58,9±7,7 kg), triglicérides (TG) (143,2±60,9 para 117,94±48,3 mg/dL). Evidenciou-se que mulheres com obesidade apresentam menor abundância dos filos pesquisados em relação às eutróficas. Ainda, a dieta hipocalórica promoveu diminuição da abundância relativa do filo Proteobacteria, o qual apresentou correlações positivas com a ingestão de lipídio total (%), ômega 6 (g). Conclui-se que a intervenção com dieta hipocalórica foi eficaz na redução de peso, IMC, MG e TG e na modulação da microbiota intestinal, com a diminuição do filo Proteobacteria / Obesity is considered a multifactorial disease and it may involve, in its genesis, genetic, metabolic, environmental, psychological and socioeconomic aspects. The expressive growth of a worldwide incidence of obesity triggers the continual emergence of new researches on this subject and, in this context, recent studies have suggested that the intestinal microbiota is a factor that may contribute to the development of this disease. Thus, there is the premise that the changes in the composition of the intestinal microbiota can be influenced by the nutritional status (obesity x eutrophy) and by the diet quality.The present study aimed at: i. comparing the proportion of the predominant phyla of the intestinal microbiota Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia and ratio Firmicutes/Bacteroidetes among degree III obese women and eutrophic women, and ii. investigating the impact of a low-calorie diet for weight loss on the intestinal microbiota composition. This was a longitudinal prospective study in which 20 women at the average age of 33 ± 3.1 years old were selected and divided into two groups: Intervention Group (IG): 10 women with grade III obesity (Body Mass Index (BMI) > 40 kg / m2) who were submitted to a nutritional intervention (a low-calorie diet) for 8 weeks, and the Control Group (CG): 10 eutrophic women (BMI from 18.5 to 24.9 kg / m2) who were not submitted to any intervention. In the IG, sampling was carried out before and after the eight-week intervention (IG) and in the CG it was carried out only in a single moment. At each sampling, weight and height were checked; BMI was calculated, body composition was analyzed, resting metabolic rate, food intake, fasting blood glucose, and lipidogram tests were performed, and fecal sample collected. The analysis of the intestinal microbiota composition in relation to a relative abundance of every phila was performed by real-time polymerase chain reaction (qPCR). After eight weeks of a low-calorie diet, some of the observed results were weight reduction (119.5 ± 10.3 to 114.9 ± 10.2 kg), BMI (43.6 ± 2.4 to 41.9 ± 2.6 kg / m2), fat body mass (FM) (62.4 ± 7.5 to 58.9 ± 7.7 kg), triglycerides (TG) (143.2 ± 60.9 to 117.94 ± 48.3 mg / dL). It was evidenced that obese women present a lower abundance of the studied phyla in relation to the eutrophic ones. Moreover, the lowcalorie diet promoted a decrease in the relative abundance of Proteobacteria phylum, which presented positive correlations with the intake of total lipid (%) and omega 6 (g). It was concluded that the intervention with a low-calorie diet was effective in reducing BMI, FM and TG and in modulating the intestinal microbiota, by reducing Proteobacteria phylum

In the general population, one in five couples experiences difficulty in conceiving a child. The role of obesity on women’s fecundity has become a focus of attention in recent years. Successful treatment of infertility through Assisted Reproductive Technology (ART) is also compromised by the presence of obesity, which occurs in 30 % of women seeking treatment. A negative correlation exists between increased body mass index (BMI) and the number of collected oocytes and a lower birth rate after ART. Furthermore, a number of studies have established that weight loss improves natural conception rates in overweight women. Whether weight management can improve success rates in overweight / obese women undergoing in vitro fertilisation (IVF) has not been studied. The purpose of this project was to explore the role of short–term weight loss on potential pregnancy outcomes in overweight / obese women undergoing IVF programme. However, to establish this relationship, we proposed to carry out two studies to assess the following: (I) The feasibility of very low calorie diet (VLCD) during IVF treatment with respect to duration, level of restriction and tolerability of the diet during hormonal down regulation in women (Chapter 2). (II) How energy restriction may affect the quality of an early embryo in diet - induced obese mice with respect to various body weight and caloric intake (Chapter 3). In study (I), women preferred a shorter dietary intervention with greater energy restriction (456 kcal per day) to gradual energy restriction (1200 kcal / day for the first week, and afterward, 456 kcal / day) prior to oocyte transfer. Women were able to comply with the VLCD during IVF treatment and both dietary groups achieved a significant weight loss (mean 6.3 %). In study (II), by using obese mice, the effect of rapid weight loss (mean 12 %) was observed after 5 days of energy restriction. Ovulation rate was greater in the Obese group (HFD) (55.6%) and equal in both Control (CD) and Energy Restricted (HF / ER) (44.4 %) groups. The HF / ER group showed higher fertilisation rate (80 %) than HFD and CD (55% and 45.5%, correspondingly). The blastocyst stage was reached by half of the cultured embryos in both HF / ER and HFD groups and 33 % in the CD group. The quality of embryos that completed blastocyst formation did not differ between groups. However, postfertilisation development in females fed a high fat diet was slower compared to CD and HF / ER groups. In conclusion, this work illustrated a weight management prior conception and use of VLCD during IVF treatment in clinical study needs further investigation with regard to the dietary duration, level of energy restriction and how this combination will influence IVF treatment outcomes. Furthermore, as we were unable to determine the question of how the dietary intervention affects the quality of oocytes and the animal study illustrated a promising result, thus further studies are required. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311579 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

In the general population, one in five couples experiences difficulty in conceiving a child. The role of obesity on women’s fecundity has become a focus of attention in recent years. Successful treatment of infertility through Assisted Reproductive Technology (ART) is also compromised by the presence of obesity, which occurs in 30 % of women seeking treatment. A negative correlation exists between increased body mass index (BMI) and the number of collected oocytes and a lower birth rate after ART. Furthermore, a number of studies have established that weight loss improves natural conception rates in overweight women. Whether weight management can improve success rates in overweight / obese women undergoing in vitro fertilisation (IVF) has not been studied. The purpose of this project was to explore the role of short–term weight loss on potential pregnancy outcomes in overweight / obese women undergoing IVF programme. However, to establish this relationship, we proposed to carry out two studies to assess the following: (I) The feasibility of very low calorie diet (VLCD) during IVF treatment with respect to duration, level of restriction and tolerability of the diet during hormonal down regulation in women (Chapter 2). (II) How energy restriction may affect the quality of an early embryo in diet - induced obese mice with respect to various body weight and caloric intake (Chapter 3). In study (I), women preferred a shorter dietary intervention with greater energy restriction (456 kcal per day) to gradual energy restriction (1200 kcal / day for the first week, and afterward, 456 kcal / day) prior to oocyte transfer. Women were able to comply with the VLCD during IVF treatment and both dietary groups achieved a significant weight loss (mean 6.3 %). In study (II), by using obese mice, the effect of rapid weight loss (mean 12 %) was observed after 5 days of energy restriction. Ovulation rate was greater in the Obese group (HFD) (55.6%) and equal in both Control (CD) and Energy Restricted (HF / ER) (44.4 %) groups. The HF / ER group showed higher fertilisation rate (80 %) than HFD and CD (55% and 45.5%, correspondingly). The blastocyst stage was reached by half of the cultured embryos in both HF / ER and HFD groups and 33 % in the CD group. The quality of embryos that completed blastocyst formation did not differ between groups. However, postfertilisation development in females fed a high fat diet was slower compared to CD and HF / ER groups. In conclusion, this work illustrated a weight management prior conception and use of VLCD during IVF treatment in clinical study needs further investigation with regard to the dietary duration, level of energy restriction and how this combination will influence IVF treatment outcomes. Furthermore, as we were unable to determine the question of how the dietary intervention affects the quality of oocytes and the animal study illustrated a promising result, thus further studies are required. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311579 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

In the general population, one in five couples experiences difficulty in conceiving a child. The role of obesity on women’s fecundity has become a focus of attention in recent years. Successful treatment of infertility through Assisted Reproductive Technology (ART) is also compromised by the presence of obesity, which occurs in 30 % of women seeking treatment. A negative correlation exists between increased body mass index (BMI) and the number of collected oocytes and a lower birth rate after ART. Furthermore, a number of studies have established that weight loss improves natural conception rates in overweight women. Whether weight management can improve success rates in overweight / obese women undergoing in vitro fertilisation (IVF) has not been studied. The purpose of this project was to explore the role of short–term weight loss on potential pregnancy outcomes in overweight / obese women undergoing IVF programme. However, to establish this relationship, we proposed to carry out two studies to assess the following: (I) The feasibility of very low calorie diet (VLCD) during IVF treatment with respect to duration, level of restriction and tolerability of the diet during hormonal down regulation in women (Chapter 2). (II) How energy restriction may affect the quality of an early embryo in diet - induced obese mice with respect to various body weight and caloric intake (Chapter 3). In study (I), women preferred a shorter dietary intervention with greater energy restriction (456 kcal per day) to gradual energy restriction (1200 kcal / day for the first week, and afterward, 456 kcal / day) prior to oocyte transfer. Women were able to comply with the VLCD during IVF treatment and both dietary groups achieved a significant weight loss (mean 6.3 %). In study (II), by using obese mice, the effect of rapid weight loss (mean 12 %) was observed after 5 days of energy restriction. Ovulation rate was greater in the Obese group (HFD) (55.6%) and equal in both Control (CD) and Energy Restricted (HF / ER) (44.4 %) groups. The HF / ER group showed higher fertilisation rate (80 %) than HFD and CD (55% and 45.5%, correspondingly). The blastocyst stage was reached by half of the cultured embryos in both HF / ER and HFD groups and 33 % in the CD group. The quality of embryos that completed blastocyst formation did not differ between groups. However, postfertilisation development in females fed a high fat diet was slower compared to CD and HF / ER groups. In conclusion, this work illustrated a weight management prior conception and use of VLCD during IVF treatment in clinical study needs further investigation with regard to the dietary duration, level of energy restriction and how this combination will influence IVF treatment outcomes. Furthermore, as we were unable to determine the question of how the dietary intervention affects the quality of oocytes and the animal study illustrated a promising result, thus further studies are required. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1311579 / Thesis (M.Med.Sc.) -- University of Adelaide, School of Paediatrics and Reproductive Health, 2008

(EN) Obesity and type 2 diabetes mellitus (T2DM) are among metabolic disease with increasing incidence and prevalence. Last decade has been devoted to intensive research focused on pathophysiological mechanisms underlying development of these diseases. Besides environmental factors, lifestyle and amount and composition of food, adipose tissue is a key player in the pathogenesis of obesity and its metabolic complications including insulin resistance (IR) and T2DM. Primary aim of our work was to evaluate the role of recently discovered adipokine omentin and the role of mitochondrial dysfunction in subcutaneous adipose tissue (SCAT) and in peripheral monocytes (PM) in patients with obesity and T2DM with respect to the development of insulin resistance and diabetes. A total number of 118 subjects enrolled in the study were divided into three groups: patients with obesity and T2DM (T2DM group), obese non-diabetics (OB) and healthy lean subjects as a control group (KO). Study subjects underwent several types of interventions - 2 to 3 weeks of very-low calorie diet (VLCD, energy intake 600 kcal per day), regular physical activity program or bariatric surgery (laparoscopic sleeve gastrectomy, LSG). Results indicate that low serum omentin concentrations may contribute to development of obesity-associated...

(EN) GH/IGF-1 axis components (GH, growth hormone receptor (GH-R), IGF-1, IGF-1 receptor (IGF-1R), IGF-binding proteins (IGFBPs)) participate in the control of glucose metabolism, inflammatory processes as well as cell proliferation and differentiation, including adipocytes and monocytes. The aim of the present study was to evaluate the role of local mRNA expression of GH/IGF-1 axis components in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) in the development of insulin resistance and differences of adipose tissue mass in following groups of patients: obese females with and without type 2 diabetes mellitus and subjects with active untreated acromegaly. A total number of 66 subjects were included in the study: obese females without type 2 diabetes mellitus (OB), obese females with type 2 diabetes mellitus (T2DM), acromegalic patients (AC) and healthy lean control subjects (C). T2DM underwent 2 weeks of very-low- calorie diet (VLCD - energy content 2500 kJ/day). According to our results we suggest that decreased mRNA expression of IGF-1, IGF-1R, IGFBP-2 and IGFBP-3 in adipose tissue of T2DM subjects may contribute to changes of fat differentiation capacity and the increased IGF-1R mRNA expression in peripheral monocytes in these patients may play a role in the regulation of...