Thesis (M.Med.Sc.) -- University of Adelaide, School of Paeddiatrics and Reproductive Health Research, Discipline of Obstetrics and Gynaecology, 2008. / "January 2008" Includes bibliographical references. Also available in print form.

Thesis (M.S.)--Florida State University, 2005. / Advisor: J. Michael Overton, Florida State University, College of Human Sciences, Dept. of Nutrition, Food, and Exercise Sciences. Title and description from dissertation home page (viewed Jan. 26, 2006). Document formatted into pages; contains vii, 34 pages. Includes bibliographical references.

Thesis (M.Sc.)--York University, 2008. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 84-103). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR51577

Made available in DSpace on 2014-06-11T19:22:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-02-10Bitstream added on 2014-06-13T20:09:53Z : No. of bitstreams: 1 santos_aca_me_prud.pdf: 682652 bytes, checksum: 7cab7fec0b1c9d2daea0c0b0a9dfa178 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente estudo objetiva investigar o efeito de um protocolo de treinamento aeróbio periodizado em natação durante seis semanas sobre o perfil biométrico, o desempenho e a morfometria cardíaca de ratos alimentados com dieta hiper e normocalórica com duração de 6 e 16 semanas. Para tanto, 103 Ratos Wistar (90 dias; 361,18 ± 34,18 g) foram divididos em duas fases de experimento. Num primeiro momento, quatro grupos (N=12) foram submetidos a seis semanas de aplicação da dieta seguida pela avaliação de parâmetros bioquímicos, adaptação ao meio líquido, avaliação da capacidade aeróbia (CA), protocolo de treinamento periodizado em natação (TPN) durante seis semanas; nova determinação da CA e por fim a eutanásia, obtendo-se o coração dos animais. Na segunda fase do experimento, outros quatro grupos (N=12) passaram pelo mesmo processo, adicionando-lhes dez semanas de administração da dieta, totalizando-se 16 semanas, e uma avaliação dos parâmetros bioquímicos antes da adaptação ao meio líquido. Os corações foram então submetidos à análise histomorfométrica... / This study investigates the effect of an aerobic swimming training periodized protocol for six weeks on biometric profile, performance and cardiac morphology in rats fed with hyper and normocaloric diets during 6 and 16 weeks. For this purpose, 103 Wistar rats (90 days; 361,18 ± 34,18 g) were divided into two stages of the experiment. Initially, four groups (N=12) underwent six weeks of diet application followed by biochemical parameters assessment, adaptation to the water, aerobic capacity assessment (AC), swimming training periodized protocol (STP) during six weeks; another AC determination and finally euthanasia, obtaining the animals hearts. In the second phase of the experiment, four groups (N=12) went through the same process by adding them ten weeks of diet administration, totaling 16 weeks, and another biochemical parameters assessment before adaptation to the water. Hearts were then submitted to histomorphometric... (Complete abstract click electronic access below)

The purpose of this study was to determine the plasma lipid variations during periods of low calorie diet and low calorie diet plus increased physical activity. Four male graduate students, with above normal activity levels, volunteered for the 10 week study which was divided into five experimental periods. The first, or control condition involved a two week period during which the subjects received a regular diet of normal foods equivalent to approximately 3600 calories per day. During this period 'normal' activity was maintained. The second treatment condition involved a 10 day period of a low calorie diet, with continued 'normal' activity. The low calorie diet was equivalent to approximately 1800 calories daily, of natural foods, plus one multiple vitamin pill. The third experimental period was similar to the control period; a two week period during which the subjects received approximately 4000 calories, per day, of the regular diet. Again, 'normal' activity was maintained. The fourth treatment condition was identical to the second experimental period with the additional requirement of increased daily energy expenditure, per subject, of 500 calories. The final experimental period consisted of a two week period of the regular diet with 'normal' activity. Blood samples were taken, following an overnight fast, twice during each experimental period: once mid-way through the period and again at the end. Plasma triglyceride and free fatty acid concentrations were measured in duplicate in each sample. The results of orthogonal comparisons among treatment means showed a statistically significant increase in the plasma free fatty acid concentration during the low calorie diet and the low calorie diet plus exercise treatment conditions. Increased mobilization of free fatty acids from adipose tissue triglycerides in response to the insufficient dietary supply of substrates for metabolism was cited as the mechanism responsible for the rise in free fatty acid concentration. Neuman-Keuls method was used to examine the effect of the increased physical activity during the low calorie diet periods; the results showed that the increased physical activity had no significant effect on the plasma free fatty acids. Similar statistical procedures applied to the plasma triglyceride values showed a significant decrease in the plasma triglyceride concentration during the low calorie diet and the low calorie diet plus increased physical activity periods. The stress of the low calorie diet on the habitually active subjects was responsible for the decreased levels. The lipid and carbohydrate content of the normal and the low calorie diets, as well as increased peripheral uptake of triglycerides, were suggested as possible explanations for the plasma triglyceride changes. The additional daily output of 500 Calories during the second stress condition was not of sufficient magnitude to elicit a further decrease in plasma triglyceride concentration. / Education, Faculty of / Curriculum and Pedagogy (EDCP), Department of / Graduate

No description available.

Thesis advisor: Thomas N. Seyfried / Dietary therapy has been used since ancient times to treat the symptoms of disease and disorder. Dietary therapy has long captured the interest of the public in modern times, dating back to the mid-nineteenth century with Englishman William Banting's "Letter on Corpulence, Addressed to the Public", which addressed Banting's anecdotal use of a high-fat diet to treat obesity. High-fat diets became popular in the United States in the early twentieth-century to treat epilepsy. The utility of dietary therapy to treat diseases and disorder has not been embraced widely, as there is a paucity of standardized clinical trials that demonstrate robust safety and therapeutic efficacy for specific diseases and disorders. Additionally, preclinical studies of dietary therapy do not adhere to standardized guidelines, which can hinder cross-study interpretation and reproducibility. To that end, my dissertation updates diet implementation guidelines for preclinical studies that adhere to standardized experimental design and biomarker monitoring in mouse models in order to maximize therapeutic efficacy, diet regimen safety, and cross-study interpretability. With these guidelines, I explored the effect of various diets on circulating glucose and ketone bodies in mice, a measure of glycolytic flux, along with biomarkers of health. I found that calorie-restricted diets, regardless of macronutrient composition, lowers circulating glucose and increases circulating ketone levels, along with improving biomarkers of health, including lowering circulating triglyceride levels. In demonstrating the utility of dietary therapy to treat disease, I also explored the mechanisms on how dietary therapy can be used to treat epilepsy in a preclinical mouse model. I showed that reduced glucose utilization underlies the seizure-protective effects of dietary therapy in EL mice, a mouse model of idiopathic epilepsy. Lastly, I developed a novel tool, the Glucose Ketone Index Calculator, to track the progress of dietary therapy in brain cancer patients through a ratio of circulating glucose to circulating ketone bodies. Evidence is presented that demonstrates a low ratio of glucose to ketone bodies is associated with improved prognosis of brain cancer management in humans and mice. Overall, this dissertation demonstrates the utility of dietary therapy in treating disease using standardized guidelines, and suggests the use of a novel tool to apply and track the progress of dietary therapy in the clinical brain cancer population. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Ageing is accompanied by numerous metabolic changes and age-related diseases. Calorie restriction (CR) is a well-established non-invasive method that reduces the rate of ageing and increases lifespan in a wide range of taxa. Previous studies have highlighted a relationship between the extent of restriction and the extent to which lifespan is increased. However, the mechanisms by which CR mediates its beneficial effects on ageing are yet to be fully understood. I therefore tested three hypotheses which examined the role of metabolic changes in the hypothalamus, the epididymal white adipose tissue and liver on the beneficial effects of CR. A three month graded CR study was performed on 5 month old male C57BL/6 mice. Six different treatments were used: 24 hours ad libitum (AL) feeding, 12 hours AL feeding, 10% CR, 20% CR, 30% CR and 40% CR. Behavioural, physiological and molecular information from each tissue of individual mice were collected. Using this comprehensive data set, I analysed the changes in the transcriptome when exposed to graded CR at both the individual gene level and also using network inferential approaches in the three tissues. My results suggest that CR leads to an overall reduction in the state of inflammation in adipose tissue which may be signalled via secreted cytokines leading to a corresponding reduction in signalling to other tissues. Signal molecules, including those from the adipose tissue, activated the hunger signalling pathway via receptors in the hypothalamus during CR. Responses to CR in the liver were consistent with several current theories reported in the literature and are likely to reflect the combined role of multiple ageing related processes. By constructing multitissue, multi-gene networks I was able to identify potential mechanisms underpinning CR. In conclusion, CR affected multiple biological processes across several different organs in a way consistent with increased healthspan.

Graduation date: 1995

Dietary manipulations and their pharmacological outcomes have been increasingly studied in neurodegenerative diseases. However, a systematic comparison among different methods in validated animal models of Alzheimer's disease is made necessary due to several different approaches applied in recent studies. Moreover, despite the large body of evidence on the effects of calorie restriction (CR) and ketogenic diets (KDs) on amyloid pathology, no consistent data is available on the effects of calorie restriction, ketogenic diet or ketone supplements on tau pathology in transgenic models of AD. Moreover, the ketogenic diet used in our studies was custom made with low carbohydrate content and rich in medium chain triglyceride (MCT) oils, known to be rapidly metabolized in the liver, resulting in sustained peripheral ketosis. Chapter 1 tested the ability of KD to induce significant ketosis in a mouse model of amyloid deposition. We showed that, despite the mild ketosis induced, KD fed APP mice presented subtle behavioral improvement shown as faster learning in the radial arm water maze, making less errors than APP mice kept on a control diet. Additionally, we observed decreased Aβ immunoreactivity in the anterior cortex of KD fed versus control fed APP mice, despite the lack of changes in congophilic deposits. Due to the mild ketosis induced, a modified ketogenic diet was devised with decreased maltodextrin content and showed greater peripheral levels of β-hydroxybutyrate. Chapter 2 investigated the effects of a ketogenic diet in two transgenic mouse models of Alzheimer's pathology. Interestingly, we found that both transgenic lines, regardless of diet, weighed less than nontransgenic mice, despite their elevated food intake. The reduced body weight may, in part, be explained by the increased locomotor activity shown by both transgenic lines in both the open field and y-maze. Moreover, KD fed mice performed significantly better on the rotarod compared to mice on the control diet independent of genotype. We did not observed KD-induced changes in spatial or associative memory in the radial arm water maze or contextual fear conditioning, respectively. Furthermore, immunohistochemical levels of amyloid, tau, astrocytic and microglial markers showed no differences between animals fed KD or the control diet. Chapter 3 studied the effects of calorie restriction on a mouse model of tau deposition. We show here that 35% body weight reduction in Tg4510 mice did not prevent increased locomotor activity in the open field, previously reported in chapter 2. Similarly, CR did not affect motor performance or spatial memory assessed by the rotarod and radial arm water maze, respectively. Interestingly, CR Tg4510 mice showed improved short-term memory tested by the novel object recognition despite spending a minimal percentage of the trial time interacting with the objects presented. However, this improvement was not observed when the test was modified to replace the objects with mice. In this case, we noticed that nontransgenic mice spent most of the trial time interacting with the novel mouse whereas Tg4510 mice spent roughly the same amount of time at any of the areas in the test chamber. Moreover, no changes in histopathological or biochemical levels of tau, astrocytic, microglial or synaptic markers were observed. Chapter 4 sought to investigate alternative approaches to inducing ketosis in the brain by either administering BHB intracerebroventricularly (i.c.v.) or by using the acetoacetate (AcAc) diester as a dietary supplement in mice. We observed that i.c.v administration of BHB in 20 months old APP mice did not affect body weight or food intake. Consistent with the lack of effects on behavioral performance, amyloid and congophilic load were not different between APP mice infused with either saline or BHB. We also found that enteral administration of AcAc diester was well tolerated and induced peripheral ketosis for at least 3 hours. Acute ketosis, however, was not sufficient to attenuate behavioral deficits in old APP mice. Chronic dietary supplementation with AcAc was tested in control tet mice and was shown to effectively induce ketosis in mice fed a diet with normal contents of carbohydrates. Nonetheless, we observed that AcAc-induced ketosis was not significantly greater than levels induced by the ketogenic diet tested in our lab. Considering that KD did not rescue behavioral or histopathological features of either amyloid or tau depositing mouse models, we anticipated that dietary supplementation with AcAc would not likely modify the phenotype of the same mouse models tested previously. Taken together, our findings show that our custom made ketogenic diet was effective in inducing and sustaining ketosis and may play an important role in enhancing motor performance in mice. However, the lack of changes on the cognitive and histopathological phenotype of the models studied suggests that KD may not be a disease modifying therapeutic approach to AD. Moreover, calorie restriction showed inconsistent effects on behavioral and histopathological outcomes of a mouse model of tauopathies. Furthermore, dietary supplementation with acetoacetate diester was successful in inducing peripheral ketosis to the same extend as a ketogenic diet even in the context of normal carbohydrate intake, suggesting that it may be of therapeutic interest for diseases of hypometabolism but not a disease modifying therapy in mouse models of Alzheimer's pathology.