This thesis investigates the relationship between smallholder farm household networks for food acquisition and agricultural production, food security and dietary quality in the Mount Elgon region of western Kenya and eastern Uganda. Food security and dietary quality were measured through calorie consumption of the female household head in a 24 hour dietary recall, the calculation the World Food Program Food Consumption Score (WFP FCS), and the calculation of the percentage of energy sourced from staples in the diet. Correlations between these indicators support that the WFP FCS is capturing elements of both sufficiency and quality of diet. Subsequent application of Ordinary Least Squares regression determines that both food acquisition networks and technology networks for agricultural production have a statistically significant positive impact upon calorie procurement across the sites included in the study. However, networks for agricultural production appear to operate differently in different locations with regard to dietary quality. Interpretation of qualitative data gathered through interviews with agricultural service sector providers and focus groups regarding these local networks for agricultural production suggests that this might be due to differences in the types of crops promoted and attitudes held regarding food security and dietary quality prevalent in these different localities. Overall, the results suggest that both food acquisition networks and agricultural production networks are important avenues through which gains in food security may be realized. However, development efforts need to be mindful of the crops and attitudes promoted by these networks to secure gains in both caloric sufficiency and dietary quality. / Master of Science / CCRA-8 (Technology Networks for Sustainable Innovation)

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

Master of Science / Department of Human Nutrition / Weiqun Wang / Weight control through either dietary calorie restriction (DCR) or exercise is associated with cancer prevention in animal models. However, the underlying mechanisms are not fully defined. Bioinformatics approaches using genomics, proteomics, and lipidomics were employed to elucidate the profiling changes of genes, proteins, and phospholipids in response to weight loss by DCR or exercise in a mouse skin cancer model. SENCAR mice were randomly assigned into 4 groups for 10 weeks: ad lib-fed sedentary control, ad lib-fed exercise (AE), exercise but pair-fed isocaloric amount of control (PE), and 20% DCR. Two hours after topical TPA treatment, skin epidermis was analyzed by Affymetrix for gene expression, DIGE for proteomics, and lipidomics for phospholipids. Body weights were significantly reduced in both DCR and PE but not AE mice versus the control. Among 39,000 transcripts, 411, 67, and 110 genes were significantly changed in DCR, PE, and AE, respectively. The expression of genes relevant to PI3K-Akt and Ras-MAPK signaling was effectively reduced by DCR and PE as measured through GenMAPP software. Proteomics analysis identified ~120 proteins, with 22 proteins significantly changed by DCR, including upregulated apolipoprotein A-1, a key antioxidant protein that decreases Ras-MAPK activity. Of the total 338 phospholipids analyzed by lipidomics, 57 decreased by PE including 5 phophatidylinositol species that serve as PI3K substrates. Although there were many impacts that we still need to characterize, it appears that both Ras-MAPK and PI3K-Akt signaling pathways are the key cancer preventive targets that have been consistently demonstrated by three bioinformatics approaches.

Doctor of Philosophy / Department of Human Nutrition / Weiqun Wang / Weight control via dietary caloric restriction and/or exercise has been demonstrated for cancer prevention. However, the underlying mechanisms are not clear. Previous studies in our lab showed that IGF-1 and IGF-1-dependent signaling were reduced by weight control. To confirm the requirement of IGF-1 reduction for cancer prevention, we restored IGF-1 in the exercised mice, which partially reversed the reduction of TPA-induced PI3K expression and PI3K-related 38:4 PI substrate. To explore the overall mechanistic impact, we further studied the effect of weight control on the profiles of lipid, gene and protein expression in TPA treated skin tissues. The mice were randomly assigned into 4 groups: ad libitum-fed sedentary control (control), ad libitum-fed exercise (AL+Exe), exercise but pair-fed at the amount of control (PF+Exe), and 20% of dietary calorie restriction (DCR). At the end of 10 weeks, the mice were treated with TPA topically for two hours. The body weights were significantly reduced in DCR and PF+Exe but not AL+Exe mice when compared with the control. Plasma and skin tissue triacylglycerides were significantly decreased in PF+Exe and DCR groups but not AL+Exe. Similar impact was found for the diacylglyceride profile in both plasma and skin tissue accordingly. Using Affymetrix microarray, 784, 223, and 152 probe sets were respectively found significantly changed by DCR, PF+Exe, and AL+Exe. PF+Exe and DCR showed similar impact on signaling pathways-related gene expression as analyzed by GenMAPP. Of the total 86 proteins identified by 2D-DIGE proteomics, 20 proteins were significantly changed by DCR. Overall, our results showed weight control via DCR or pair-fed exercise rather than exercise with ad libitum feeding significantly reduced body weight and body fat, resulting in reduction of IGF-1 and IGF-1-induced signaling such as PI3K and PI-related pathway. The overall impact upon lipid profiling and gene and protein expression by weight loss suggests many other mechanistic targets. Although we could not ambitiously clarify all the changes were related to anticancer mechanisms in the scope of this study, understanding of the relationship between weight control and TPA-induced skin cancer risk as well as IGF-1-dependent signaling pathways may reveal intrinsic mechanisms and provide novel approaches to prevent cancer in the future studies.

Call number: LD2668 .T4 1986 N47 / Master of Science / Human Nutrition

Thesis advisor: Thomas N. Seyfried / Epilepsy is a prevalent disabling chronic and socially isolating neurological disorder that involves recurrent abnormal discharges of neurons. Despite seizures afflicting about 10% of people worldwide, antiepileptic drugs (AEDs) are largely unable to manage seizures in many persons with epilepsy. As an alternative to AEDs, dietary therapies possess a broad therapeutic potential in both humans and animals models of various neurological and neurodegenerative disease etiologies. My research focus was to identify the therapeutic efficacy and potential mechanism(s) of action of calorie restriction (CR) and the ketogenic diet (KD) in both the epileptic EL mouse model and the Mecp2<super>308/y<super/> mouse model of Rett syndrome. My findings indicate that both the KD and CR can reduce seizure susceptibility in EL mice, a natural model for multifactorial idiopathic generalized epilepsy. CR and circulating glucose and ketone levels significantly influence the therapeutic efficacy of the KD. A concurrent reduction in circulating plasma glucose levels and elevation in circulating plasma &beta-hydroxybutyrate levels was predicted to associate with the anticonvulsant effect of these diets in EL mice. For the first time, I was able to show that a KD fed in unrestricted amount is able to reduce seizure threshold in EL mice. Interestingly, supplementation of calories in the form of carbohydrate in the water of calorie-restricted EL mice results in a diminished anticonvulsant efficacy of the KD. In my effort to elucidate the neuroprotective mechanism(s) associated with these changes in metabolite availability, I started investigating the complex alterations occurring in multiple integrated neural and metabolic processes. Furthermore, I showed that a restricted KD diet improves aspects of the behavioral abnormalities seen in Rett mice, in particular with respect to anxiety. Finally, for the first time, I provide a standardized protocol for the implementation of diet therapies in the management of an array of neurological and neurodegenerative diseases, which ultimately may help elucidate the complex neuroprotective mechanism(s) of CR and the KD. This research overall has provided a new understanding in the therapeutic efficacy of diets in epilepsy and Rett Syndrome. / Thesis (PhD) — Boston College, 2010. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

O envelhecimento envolve um progressivo declínio na eficiência metabólica dos sistemas biológicos ao longo do tempo. Embora não possa ser evitado, o envelhecimento pode ter seus fenótipos típicos mitigados em organismos submetidos à restrição calórica, um regime dietético que consiste em uma oferta diminuída de calorias. Ao longo do tempo, a levedura Saccharomyces cerevisiae mostrou-se um importante organismo modelo para o estudo de importantes marcas relacionadas ao envelhecimento, sobretudo por ser responsiva à restrição calórica. Através de uma abordagem do metabolismo energético e do estado de óxido-redução celular, nós temos buscado identificar quais são os fatores imprescindíveis para a exibição do aumento do tempo de vida cronológico dessa levedura. Nós verificamos que defeitos específicos na síntese de nicotinamida adenina dinucleotídeo aumentam a geração mitocondrial de espécies reativas de oxigênio pela enzima dihidrolipoil desidrogenase, porém não suprimem o aumento da do tempo de vida cronológico de S. cerevisiae. Por outro lado, os mutantes dessa levedura irreponsíveis à restrição calórica são aqueles que possuem defeitos no metabolismo aeróbico, mais especificamente na montagem da cadeia de transporte de elétrons. Também verificamos que diferentes mutações em enzimas do ciclo dos ácidos tricarboxílicos alteram a taxa de perda do DNA mitocondrial de S. cerevisiae numa forma dependente da concentração inicial de glicose nos meios de cultura e também do tempo de cultivo. Também observamos que a eficiência energética em S. cerevisiae cultivada sob restrição calórica é aumentada em relação à levedura cultivada em condição controle. Finalmente, também observamos que a morfologia mitocondrial é alterada pelo estado metabólico celular e se correlaciona com a geração de espécies reativas de oxigênio nesse organismo. Assim sendo, em conjunto, esses dados revelam importantes modificações metabólicas e no estado de óxido redução proporcionadas pela restrição calórica e como os fenótipos típicos do envelhecimento podem ser mitigados em S. cerevisiae, assim como quais são os fatores imprescindíveis para a resposta dessa levedura à restrição calórica. / Aging involves a progressive decline in metabolic efficiency of biological systems over time. Although it cannot be avoided, aging phenotypes are delayed in organisms undergoing caloric restriction, a dietary regimen consisting of a reduced availability of calories. The yeast Saccharomyces cerevisiae has proved to be an important model organism for studying important characteristics related to aging, and is responsive to caloric restriction. We sought to identify factors essential for increased chronological lifespan in yeast by investigating changes in energy metabolism and redox state. We found that defects in the synthesis of nicotinamide adenine dinucleotide increased mitochondrial generation of reactive oxygen species by the enzyme dihidrolipoil dehydrogenase, but did not suppress the increase in chronological life span. On the other hand, mutants of this yeast which do not respond to caloric restriction are those that have defects in aerobic metabolism, specifically in the assembly of the electron transport chain. We also found that different mutations in enzymes of the citric acid cycle alter the rate of loss of mitochondrial in a manner dependent on the initial concentration of glucose in culture media and culture time. We also observed that energy efficiency in S. cerevisiae grown under caloric restriction is increased compared to yeast grown under control conditions. Finally, we also observed that mitochondrial morphology is altered by the cellular metabolic state and correlates with the generation of reactive oxygen species in this organism. Thus, altogether, these data reveal significant changes in metabolism and redox state promoted by caloric restriction, how phenotypes typical of aging can be prevented in S. cerevisiae, as well as what factors are required for the response of yeast to caloric restriction.

Neste estudo, avaliamos o efeito da restrição calórica e do treinamento resistido na massa corporal e na sensibilidade à insulina de ratas ovariectomizadas. 80 ratas fêmeas da linhagem Holtzman foram distribuídas em 8 grupos (n=10 cada): ovariectomizado (OVX), ovariectomizado com restrição calórica (OVX RC), ovariectomizado com treinamento resistido (OVX TR), ovariectomizado com restrição calórica e treinamento resistido (OVX TR+RC), Sham operado (SHAM), Sham com restrição calórica (SHAM RC), sham com treinamento resistido (SHAM TR), sham com restrição calórica e treinamento resistido (SHAM TR+RC). Após 13 semanas de intervenção, foram analisados: massa corporal, gordura corporal; concentrações sanguíneas de glicose, insulina e adiponectina; conteúdo de AKT total e fosforilada, pi3k e Glut 4 (nos tecidos adiposos subcutâneo e retroperitoneal). As ratas ovariectomizadas (OVX, OVX RC, OVX TR e OVX TR+RC) apresentaram maior massa corporal e gordura corporal quando comparadas ao grupo SHAM. As concentrações de glicose e insulina foram semelhantes em todos os grupos experimentais, porém a concentração de adiponectina foi menor nos grupos ovariectomizados (OVX, OVX RC, OVX TR e OVX TR+RC), quando comparados ao grupo SHAM. A RC e o TR aumentaram a concentração de adiponectina quando comparado ao grupo OVX. Não houve diferença entre os grupos em relação à via de sinalização da insulina nos tecidos adiposos subcutâneo e retroperitoneal. Concluímos que a ovariectomia causa aumento de massa e gordura corporal, levando à menor concentração de adiponectina, e que a RC e o TR alteram estas modificações. / In this study, we evaluated the effect of calorie restriction and strength training on the body weight and insulin sensitivity of ovariectomized rats. Eighty female Holtzman rats were divided into eight groups (n=10 per group): ovariectomized (OVX), ovariectomized plus calorie restriction (OVX-CR), ovariectomized plus strength training (OVX-ST), ovariectomized plus strength training and calorie restriction (OVX-ST+CR), sham operated (SHAM), sham plus calorie restriction (SHAM-CR), sham plus strength training (SHAM-ST), and sham plus strength training and calorie restriction (SHAM-ST+CR). The following variables were analyzed after 13 weeks of intervention: body weight; body fat; blood concentrations of glucose, insulin and adiponectin; total and phosphorylated AKT content; pi3k and Glut 4 (in subcutaneous and retroperitoneal adipose tissues). Ovariectomized rats (OVX, OVX-CR, OVX-ST, and OVX-ST+CR) had a higher body weight and body fat than SHAM animals. Glucose and insulin concentrations were similar in all experimental groups, but adiponectin concentration was lower in the ovariectomized groups (OVX, OVX-CR, OVX-ST, and OVX-ST+CR) when compared to the SHAM group. Calorie restriction and ST increased the concentration of adiponectin when compared to the OVX group. There was no difference between groups in terms of insulin signaling in subcutaneous or retroperitoneal adipose tissue. We conclude that ovariectomy increases body weight and body fat, reducing adiponectin concentration, and that CR and ST alter these modifications.