Obesity is one the few modifiable risk factors for breast cancer. Hence, an evaluation of the metabolic and cancer inhibitory effects of the obesity reversing strategies, calorie restriction (CR) and exercise, is important for breast cancer prevention. Additionally, a better understanding of the mechanisms underlying the effects of these interventions on cancer will provide scientific basis for therapeutic recommendations, and facilitate the identification of therapeutic agents for breast cancer treatment in obese patients. We found that CR is more effective than exercise in reversing the metabolic and cancer enhancing effects of obesity. Even at comparable levels of adiposity, CR effects on insulin resistance, energy balance related hormones levels, and metabolic genes expression in adipose tissue were more profound than those of exercise. The mechanism by which CR influences tumor progression is thought to involve molecules that respond to energy balance changes and control cell growth, such as the insulin-like growth factor-1 (IGF-1) and the mammalian target of rapamycin (mTOR). The mTOR inhibitor rapamycin decreased mammary tumor burden to levels comparable to CR. While established tumors did not display decreased mTOR activity, constitutively active mTOR was capable of overcoming some of the inhibitory effects of CR on tumor cells invasion and migration. Effects of increasing levels of CR on gene expression indicate that 30% and 40% CR, but not 20% CR, induce beneficial metabolic changes in the liver. However, 40% CR also increases apoptosis of hepatic cells which appears to be detrimental for the liver. IGF-1 infusion partially overcame the beneficial effects of CR on expression of tumor-related genes in the mammary fat pad and on mammary tumor growth. Taken together, our data show that CR, but not exercise, is able to reverse the metabolic and tumorigenic effects of obesity. Furthermore, the IGF-1 and mTOR pathways may mediate, at least in part, many of the beneficial effects of CR on metabolism and tumor progression. / text

Obesity is an established risk and progression factor for many types of cancer, including pancreatic and colon cancer, and is characterized by abnormal metabolic hormone production and a chronic low-grade state of inflammation. However, the links between obesity, hormones, inflammation and tumorigenesis in colon and pancreatic tissue are poorly understood. Calorie restriction (CR), an anti-obesity dietary regimen with potent anticancer effects, reduces serum metabolic hormones and protumorigenic cytokines. Insulin-like growth factor (IGF)-1 is a metabolic hormone that activates NF-[kappa]B, a key regulator of inflammation. NF-[kappa]B is a transcription factor that mediates transcription of many cancer- and inflammation-related genes and is upregulated in both colon and pancreatic cancer. We hypothesized that CR inhibits colon and pancreatic tumor cell growth through modulation of hormone-stimulated NF-[kappa]B activation and protumorigenic gene expression. To test this hypothesis, we used CR and ad libitum feeding to generate a lean and overweight (control) phenotype, respectively; in C57BL/6 mice transplanted with MC38 colon cancer cells or Panc 02 pancreatic cancer cells, and analyzed the effect of diet on circulating hormone levels, markers of inflammation, and tumor growth. We also investigated the in vitro effects of IGF-1 on NF-[kappa]B activation and downstream protumorigenic gene expression in MC38 and Panc 02 cells. CR, relative to control diet, reduced body weight, circulating IGF-1 levels, and transplanted MC38 and Panc 02 tumor growth, as well as protumorigenic gene expression in the MC38 and Panc 02 tumor microenvironment. IGF-1 increased cell viability, NF-[kappa]B nuclear translocation and DNA binding, transcriptional activation, and downstream gene expression of inflammation and other protumorigenic genes in MC38 colon cancer cells and Panc 02 pancreatic cancer cells in vitro. Knockdown studies of NF-[kappa]B in Panc 02 cells using si-RNA established that the IGF-1-induced increase in protumorigenic gene expression is mediated, at least partially, through an NF-[kappa]B-dependent mechanism. In conclusion, these findings in models of pancreatic and colon cancer help clarify the links between obesity, IGF-1, NF-[kappa]B-mediated inflammation, and cancer. This work provides the underpinnings for several new molecular targets and strategies to test in model systems and translational studies for preventing or controlling obesity-related cancer. / text

Thesis (M.A.)--Mahidol University, 1982.

Calorie restriction (CR) is one of the few treatments that has been observed to significantly extend life in a wide variety of species. While its life-extending properties are still being investigated in primates, there is general agreement that it reduces oxidative stress and inflammation. Interestingly, there is some evidence that it may ameliorate or delay the onset of a number of neurodegenerative diseases, including age-related white matter degeneration. The processes underlying its neuroprotective effects in non-human primates are unknown, but oxidative stress and inflammation are potential contributors to age-related white matter pathologies that characterize aging in the monkey brain and correlate with cognitive decline. To determine if CR reduces damage due to oxidative stress and inflammation in the monkey brain, brains from four calorie restricted monkeys and four matched controls brains were processed for immunohistochemical analysis using an antibody against the pro-inflammatory protein S100b. S100b is a widely expressed calcium-binding cytoplasmic protein associated with neurological insults like ischemia, atrophy, and neurofibrillary tangles and plaques in Alzheimer's disease. It is primarily expressed in astrocytes, but is also expressed to a lesser extent in microglia, oligodendrocytes, and some neuronal populations. Stereology was used to estimate density of S100b labeling in the cingulum, corpus callosum and visual cortex. No significant difference between calorie restricted animals and controls was found. More specific markers of oxidative stress and inflammation may be more effective in revealing any significant differences between CR and control brains. Potential alternatives include antibodies against 4-hydroxynonenal, a lipid peroxidation product, and encephalitogenic peptides of myelin basic protein, which are only exposed to the extracellular environment when myelin is damaged.

Recently, Magnetic Resonance Imaging (MRI) has found great traction in monitoring the effects of Caloric Restriction (CR) on the brain, specifically gray matter. However, there are no streamlined, simple pipelines in existence to analyze data generated from these kinds of MRI studies. Therefore, my hypothesis is two-fold: the first part being the development of a dynamic and straightforward image processing pipeline, which I have tailored to fit the unique needs of the CR data involved in this study. This data brings me to the second part of my hypothesis, which is to use that pipeline to highlight the decreased attenuation in grey matter induced by long-term CR. In order to test the second portion of my hypothesis, T1/MPRAGE scans were collected from 17 male Rhesus Macaques, half of which were maintained on a 30% reduced calorie diet for an average of 22 years, starting around age 3. Using this basis, the inherent properties of the MR images were exploited by the novel pipeline, and used to analyze whether or not CR reduces the attenuation of grey matter atrophy, with regards to aging

This thesis investigates self-tracking practices of users of MyFitnessPal calorie counting app. The thesis researches everyday self-trackers users who have started using the app on their own and are not part of any self-tracking community and focuses on the practices of self-tracking. The thesis responds to the literature on self-tracking that has often neglected everyday self-trackers and practices of self-tracking. First, many studies, whether sociological investigations or human-computer interaction research, focus on members of Quantified Self (QS) community (Choe, Lee, Lee, Pratt, & Kientz, 2014; Li, Dey, & Forlizzi, 2010; Neff & Nafus, 2015; Sharon & Zandbergen, 2016). QS is a community of individuals who are interested in learning more about themselves through, oftentimes unusual and complex, self-tracking, which involves modification of existing technologies or even creation of new ones. Thus, focusing on QS members neglects the individual everyday self-trackers, their experiences and practices. Second, existing studies have mainly focused on health or social implications of self-tracking (Lupton, 2012b, 2013d, 2014a, Swan, 2012b, 2013). These include, but are not limited to, potential of self-tracking to assist diagnosis (Wile, Ranawaya, & Kiss, 2014), or behaviour change (Chiauzzi, Rodarte, & Dasmahapatra, 2015), self-tracking increasing surveillance, public pedagogy (Rich & Miah, 2014) and subjection to neoliberal values and promotion of healthism (Lupton, 2012b, 2013a) or leading to monetisation of exercise (Till, 2014). While these studies have yielded important insights, they do not help us to understand what people actually do when they self-track, i.e. what practices self-tracking involves and how people engaged in self-tracking manage them. Guided by the STS approach that highlights the importance of observing the mundane practices and need to focus on technology users, this thesis explores the practices of everyday self-trackers. The exploration of the practices of self-tracking among the everyday self-trackers is based on 31 interviews with early mid-life individuals, who were mainly recruited from gyms and shared their self-tracking experience of using the MyFitnessPal calorie counting app. The analytical chapters answer three questions: What is self-tracking by calorie counting in the everyday like? How is self-tracking by calorie counting done? What are the practices through which self-tracking affects those engaged in it? To answer the first question, I juxtapose self-tracking goals, use and effects as they are represented in the literature on the QS to those of my participants. Doing this reveals that self-tracking in the everyday is perceived and done quite differently than the QS metaphor would allow us to believe. The goals of the participants are mundane (weight loss), they do not use the sophisticated features of the app and are not interested in the historical data, the effects of the app are not life-changing and temporary closely tied to the use of the app. This stands in contrast to QS metaphor where self-tracking is geared towards continuous self-improvement, driven by intricate data analysis and biohacking. To answer the second question, I focus on self-tracking by calorie counting with MyFitnessPal as a dieting practice. I explore how self-tracking affects the daily practices as well as is incorporated in participants lives. The users, thus, aim to find an approach to temporal aspects of tracking and precision that would fit most conveniently with their other daily practices. They manipulate their use of the app to accommodate any meals that are not in their usual dieting routine. This highlights that dieting through self-tracking is not a straightforward data collection and involves practical strategies and negotiations, and can both influence and be influenced by other everyday practices. The third question focuses on quantification, that is the production and communication of numbers (W. N. Espeland & Stevens, 2008, p. 402). Quantification has usually been discussed at institutional levels, in terms of government, science or, in the case of Espeland and Sauder s (W. N. Espeland & Sauder, 2007) seminal work, in terms of academic rankings. I adopt the insights from these studies to make sense of the quantification at the individual level using MyFitnessPal. I draw out two features of individual quantification that distinguish it from institutional one, mainly that quantification is done for oneself only and it relies on self-governance. Further, I outline how quantification affects such decisions as whether to eat, what to eat and how much to eat. Quantification also works as commensuration as participants compared different foods referring to their calorie value. However, unlike in the case of institutional quantification, individual quantification did not have to be accepted unquestionably and often other values of food would be weighted in relation to calories when participants made choices what to eat. Ultimately, this thesis contributes a new perspective on self-tracking as it explores the mundanity of it. It adds fine-grained insights into the everyday practices of self-tracking by adopting a novel analytical angle that centres on practices and by exploring a neglected user group of everyday self-trackers.

Orientador: José Carlos Silva Camargo Filho / Banca: Luiz Carlos Marques Vanderlei / Banca: Francis da Silva Lopes / Resumo: 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... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: 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) / Mestre

Obesity is considered to be a worldwide epidemic disease characterized by an accumulation of AT. Increased adiposity can perturb normal metabolic functions and lead to the development of diseases like insulin resistance and other metabolic disorders. A large amount of clinical studies have been shown that changes in inflammatory signaling in adipose tissue cells, increased infiltration of immune cells into AT as well as stress of endoplasmic reticulum belong to the key molecular steps leading to the development of metabolic disturbances associated with this disease. Adverse metabolic effects of AT accumulation can be diminished by calorie restriction resulting in weight loss. In addition, stress of endoplasmic reticulum could be alleviated by chemical chaperones including bile acids. These two approaches for the treatment of obesity or the obesity-associated disturbances were basis for this PhD thesis. In the first part of this work, we studied inflammation status of gluteal in comparison with abdominal AT and differentiation and secretory capacity of adipocytes after weight loss in obese patients. We revealed that inflammatory profile of gluteal AT, estimated by mRNA level of macrophages and cytokines as markers of inflammatory status of the body, did not explain the different clinical impact of...

abstract: The increase in obesity since the 1980's has been associated with fast-food consumption. In hopes that calorie labeling will be an effective tool to combat obesity, congress included a provision in the Patient Protection and Affordable Care Act of 2010 (ACA) that will require all restaurants with twenty or more locations to post calorie information for each menu item. Current research has provided mixed results regarding the effectiveness of calorie labeling, but overall seems to suggest that calorie labeling may only be effective among certain populations. In September, 2012 McDonald's began to post calorie labels on their menu boards before it was federally mandated under the ACA. This policy provided the opportunity to study the impact of calorie labeling on the purchasing behavior of McDonald's patrons. This cross-sectional study was designed to determine if self-perception of diet, self-perception of health, smoking, physical activity, fruit and vegetable intake, or knowledge of daily calorie requirements is associated with the likelihood of noticing or using calorie labels, or total calories purchased. In addition, relationships between noticing or using calorie labels with total calories purchased were also examined. Receipts and survey responses were collected from 330 participants who purchased food and beverage items from 27 different McDonald's locations within a 20 mile radius of downtown Phoenix, Arizona. Results indicated that only 16.1% of the sample reported using calorie labels, and those who reported using calorie labels purchased an average of 136 fewer calories. Multivariate analysis indicated there were no statistically significant relationships between self-perception of diet, self-perception of health, smoking, physical activity, fruit and vegetable intake, or knowledge of daily calorie requirements with the likelihood of noticing or using calorie labels, or total calories purchased. However, it is possible that the small sample size of participants using calorie labeling precluded any statistically significant relationships among these variables from emerging. Further research with larger sample sizes should be conducted, to investigate individual level factors that may be associated with use of calorie labeling. / Dissertation/Thesis / M.S. Nutrition 2013

Although calorie information at the point-of-purchase at fast food restaurants is proposed as a method to decrease calorie choices and combat obesity, research results have been mixed. Much of the supportive research has weak methodology, and is limited. There is a demonstrated need to develop better techniques to assist consumers to make lower calorie food choices. Eating at fast food restaurants has been positively associated with weight gain. The current study explored the possibility of adding exercise equivalents (EE) (physical activity required to burn off the calories in the food), along with calorie information as a possible way to facilitate lower calorie choice at the point-of-choice in fast food restaurants. This three-group experimental study, in 18-34 year old, overweight and obese women, examines whether presenting caloric information in the form of EE at the point-of-choice at fast food restaurants, will lead to lower calorie food choices compared to presenting simple caloric information or no information at all. Methods: A randomized repeated measures experiment was conducted. Participants ordered a fast food meal from Burger King with menus that contained only the names of the food choices (Lunch 1). One week later (Lunch 2), study participants were given one of three menus that varied: no information, calorie information, or calorie information and EE. Study participants included 62 college aged students. Additionally, the study controlled for dietary restraint by blocking participants, before randomization, to the three groups. Results: A repeated measures analysis of variance was conducted. The study was not sufficiently powered, and while the study was designed to determine large effect sizes, a small effect size of .026, was determined. No significant differences were found in the foods ordered among the various menu conditions. Conclusion: Menu labeling alone might not be enough to reduce calories at the point-of-choice at restaurants. Additional research is necessary to determine if calorie information and EE at the point-of-choice would lead to fewer calories chosen at a meal. Studies should also look at long-term, repeated exposure to determine the effectiveness of calories and or EE at the point-of-choice at fast food restaurants.