bjetivo. Evaluar la asociación entre síndrome metabólico (SM) y carga glicémica (CG) de la ingesta alimentaria en niños y adolescentes obesos atendidos en consulta endocrinológica de un hospital de referencia pediátrica en Lima, Perú. Población y método. Estudio transversal en niños y adolescentes obesos (índice de masa corporal ≥ percentil 95) de 10 a 15 años. Se clasificó como SM según los criterios de la International Diabetes Federation. Se aplicó un recordatorio de 24 horas y se calculó la CG total y por comida. Se evaluó la asociación entre los terciles de CG (comparación con el inferior) y SM usando razones de prevalencia ajustadas (RPa) por variables demográficas, antecedentes familiares, de actividad física y consumo total de carbohidratos en modelos de regresión de Poisson con varianza robusta. Resultados. De 273 niños y adolescentes obesos, 52,4% fueron varones y 94,9% fueron físicamente inactivos. La mediana de CG fue de 213 (164,8- 287,4) y la de ingesta calórica diaria fue 2275 (1851-3024) kcal, dada principalmente por carbohidratos (62%). La prevalencia de SM fue de 22,3%; los componentes con mayor prevalencia fueron la obesidad abdominal (81,7%) y los valores de lipoproteínas de alta densidad (HDL, del inglés high density lipoprotein) bajos (63,7%). Por último, se encontró una asociación entre el consumo elevado de CG y el riesgo de presentar SM (RPa 4,5; IC 95%: 1,3-15,3). Conclusiones. Existe una asociación entre el alto consumo de CG y la presencia de SM en niños y adolescentes con obesidad. / Objective. To study the association between the metabolic syndrome (MS) and the glycemic load (GL) of food intake among obese children and adolescents seen in consultation by the endocrinology team in a pediatric referral hospital in Lima, Peru. Population and Method. Cross-sectional study among obese children and adolescents (body mass index ≥ 95 percentile), 10-15 years old. The MS was classified according to criteria of the International Diabetes Federation. A 24 hour reminder was used, and the overall and per meal GL was calculated. The association between the GL tertiles (comparison with the lower tertile) and the MS was assessed using prevalence ratios adjusted by demographic outcome measures, family history, physical activity and total carbohydrate consumption in Poisson regression models with a robust variance. Results. Out of 273 obese children and adolescents, 52.4% were male and 94.9% did not engage in any physical activity. Glycemic load median value was 213 (164.8-287.4) and the daily calorie intake value was 2275 (1851-3024) kcal, consisting mainly of carbohydrates (62%). MS prevalence was 22.3%; the most prevalent components were abdominal obesity (81.7%) and low values of high density lipoprotein (HDL) (63.7%). Lastly, an association was observed between a high consumption of GL and the risk of developing MS (aRP 4.5; 95% CI: 1.3-15.3). Conclusions. There is an association between a high consumption of GL and the presence of MS among obese children and adolescents.

Emerging evidence suggests that sedentary behaviour is independently associated with cardiometabolic disease risk in school-aged children and youth. This thesis includes 4 related studies in the pursuit of 2 objectives: 1) To determine the cross-sectional association of sedentary time, interruptions in sedentary time, sedentary bout length, and total movement variability with markers of cardiometabolic disease risk among children and youth, and 2) To examine the impact of 1-day of prolonged sedentary behaviour, with and without interruptions or structured physical activity, on markers of cardiometabolic disease risk, hunger, food intake and spontaneous physical activity levels in children and youth. In Study 1, we found that interruptions in sedentary time and short bouts of sedentary time were beneficially associated with clustered cardiometabolic disease risk in boys and girls aged 8-11 years, independent of total sedentary time, moderate-and-vigorous physical activity (MVPA), and other confounders (all p<0.05), while the opposite was true for screen based sedentary behaviours. In Study 2, we found that movement variability (minute-to-minute changes in movement intensity) was negatively associated with clustered cardiometabolic disease risk and systolic blood pressure independent of MVPA, sedentary time and other covariates in a representative sample of American children and youth aged 12-17 years (all p<0.05). In Studies 3 and 4, we found that prolonged sitting, with or without interruptions and structured MVPA did not result in acute changes in markers of cardiometabolic disease risk, nor subsequent ad libitum food intake or physical activity levels in healthy children aged 10-14 years (all p ≥0.05). Taken together, the studies that make up this thesis suggest that optimal levels of cardiometabolic disease risk are most likely to be seen in children who limit their time engaging in screen-based sedentary behaviours, who frequently interrupt their sedentary time, and who have high levels of variability in their movement behaviours.

Watching television or listening to music during exercise has been shown to increase the enjoyment of the activity and decrease fatigue for some people. However, it is currently unknown how these stimuli during an exercise session play a role in postexercise energy intake and/or physical activity energy expenditure (PAEE). The purpose of this thesis was to examine the effects of watching television or listening to music while exercising on post-exercise energy intake and expenditure in male adolescents. The study consisted of a randomized crossover design involving 24 male adolescents aged 12 to 17 years. The participants completed three experimental sessions that included walking/jogging on a treadmill at 60% of their heart rate reserve for 30 minutes while watching television, listening to music, or exercising with no other stimulus (control). Following the exercise sessions participants were given an ad libitum lunch and were asked to record their food intake for the remainder of the day. An Actical accelerometer was used to assess PAEE until bedtime. The primary outcome measure was post-exercise energy intake and energy expenditure. Results showed that exercising while watching television or listening to music did not significantly affect postexercise energy intake or energy expenditure. Walking/jogging on a treadmill was found to be more enjoyable while watching television than with no stimulus present (p=0.03). Ratings of perceived exertion were not significantly different between conditions. Overall, our results suggest that watching television or listening to music while exercising does not impact post-exercise energy intake or expenditure in male adolescents, which may have positive implications for adolescents who may need additional motivation to exercise.

京都大学 / 0048 / 新制・論文博士 / 博士(人間健康科学) / 乙第13064号 / 論人健博第3号 / 新制||人健||3(附属図書館) / (主査)教授 高桑 徹也, 教授 三谷 章, 教授 横出 正之 / 学位規則第4条第2項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM

No description available.

No description available.

No / Bariatric surgery has emerged as an increasingly popular weight loss intervention, with larger and more endurable weight loss compared to pharmacological and behavioural interventions. The degree of weight loss patients experience varies, between individuals, surgeries and over time. An explanation as to why differing weight loss trajectories exist post-surgery could be due to the complex interplay of individual differences in relation to eating behaviours and appetite. Thus the aim of this narrative review is to explore literature between 2008 and 2018, to assess the impact of impact of bariatric surgery on food selection and nutrient status, on eating behaviour traits and on disturbed and disordered eating behaviour, to determine their impact of weight loss success and weight loss trajectories. Immediately post-surgery, up until 1–2 years post-surgery, there is a reliance upon the surgery's alteration of the gastrointestinal tract to control food intake and subsequently lose weight. Energy intake is reduced, dietary adherence is higher, supplement intake is higher, appetite ratings are lower, there is a reduction in psychopathology, and an increase in wellbeing. After this point, patients become more susceptible to weight regain, as this is the point where passive observation of the weight reducing action of surgery, moves into more cognitive effort, on the part of the individual, to control energy intake. There are various factors which influence an individual's ability to successfully regulate their energy intake post-surgery, such as their level of Disinhibition, Restraint, Hunger, Emotional Eating, Uncontrolled Eating, psychopathology and wellbeing. The need for continued psychological and nutritional support post-surgery is necessary to reduce weight regain susceptibility.

Type 2 diabetes (T2D) is one of the fasting growing chronic diseases, caused by insulin resistance and pancreatic β-cell dysfunction. While over thirty medications were approved to treat T2D in the United States, less than one in four patients treated with anti-diabetic drugs achieved the glycemic target. Thus, identifying more effective anti-diabetic drugs is still needed for improving glycemic control in T2D patients. Incretins are gut hormones that possess potent insulinotropic action, which have drawn considerable attention in research and developing treatment strategy for T2D. Specifically, glucagon like peptide 1 (GLP-1), the most important incretin that is secreted from enteroendocrine L-cells in response to food ingestion, plays a vital role in maintaining glycemic homeostasis via potentiating glucose stimulated insulin secretion (GSIS) and promoting pancreatic β-cell proliferation and survival. Therefore, targeting L-cells to induce GLP-1 secretion would be an alternative strategy for treating T2D. The goal of this research was to identify low-cost and safe naturally occurring agents as a primary or adjuvant treatment for T2D. Here, I found that a small molecule, elenolic acid (EA), which was generated in our lab but is also present in mature olive and extra virgin olive oil, dose-dependently stimulated GLP-1 secretion in mouse clonal L-cells and isolated mouse ileum crypts. EA induced a rapid increase in intracellular [Ca2+]i and the production of inositol trisphosphate in L-cells, indicating that EA activates phospholipase C (PLC)-mediated signaling. Consistently, inhibition of (PLC) ablated EA-stimulated increase of [Ca2+]i and GLP-1 secretion in L-cells. In addition, EA-triggered GLP-1 secretion from L-cells was blocked by YM-254890, a Gαq inhibitor. Consistent with our in vitro study, a single dose of EA acutely stimulated GLP-1 secretion in mice, accompanied with an improved oral glucose tolerance. Chronic administration of EA restored the impaired glucose and lipid homeostasis in DIO mice, which may be partially due to promoting GLP-1 secretion and reduced hepatic gluconeogenesis. In addition, EA suppressed appetite, reduced food intake and gastric emptying rate, as well as promoted weight loss in obese mice, demonstrating that it is also an anti-obesity agent. Further, EA treatment reduced lipid absorption, and promoted hepatic fatty acid oxidation, and reversed abnormal plasma lipid profiles in DIO mice. Consistently, EA exerted potent anti-diabetic action in db/db mice, and its blood glucose-lowering effect is comparable with that of liraglutide in blood glycemic control but is better than that of metformin in this overt diabetic model. Collectively, I have identified for the first time, as to the best of our knowledge, that EA could be a dual-action compound that exerts anti-diabetic effects via activation of the GLP-1 mediated metabolic pathway and suppression of hepatic gluconeogenesis, leading to effective control on food intake, body weight gain, and glycemia in T2D mice. / Doctor of Philosophy / Type 2 diabetes (T2D) is one of the fasting growing chronic diseases, which results from insulin resistance and pancreatic β-cell dysfunction. Even though there have been over thirty drugs approved to treat T2D in the United States, less than 25% of patients treated with anti-diabetic drugs achieved the glycemic target. Thus, more effective anti-diabetic drugs are still needed for improving glycemic control in patients with T2D. Incretins are a group of gut hormones and responsible for over 50% postprandial insulin secretion in humans, which have drawn considerable attention in research and developing a treatment strategy for T2D. Specifically, glucagon-like peptide 1 (GLP-1), the most important incretin that is secreted from enteroendocrine L-cells in response to food ingestion, plays a vital role in controlling blood glucose via potentiating glucose-stimulated insulin secretion (GSIS) and promoting pancreatic β-cell proliferation and survival. Therefore, targeting L-cells to induce GLP-1 secretion would be an alternative strategy for treating T2D. The goal of this research was to identify low-cost and safe naturally occurring agents as a primary or adjuvant treatment for T2D. Here, I found that a small molecule, elenolic acid (EA), which was synthesized in our lab but is also present in mature olive and extra virgin olive oil, dose-dependently stimulated GLP-1 secretion in mouse clonal L-cells and isolated mouse ileum crypts (containing L-cells). Further experiments showed that EA induced a rapid increase in intracellular [Ca2+]i and the production of inositol trisphosphate (IP3) in L-cells, indicating that EA activates phospholipase C (PLC)-mediated signaling, as IP3 is a direct product of PLC. Consistently, inhibition of PLC ablated EA-stimulated increase of [Ca2+]i and GLP-1 secretion in L-cells. In addition, EA-triggered GLP-1 secretion from L-cells was blocked by YM-254890, a Gαq inhibitor. In line with the in vitro study, a single dose of EA acutely elevated plasma GLP-1 concentration in mice, accompanied by improved oral glucose tolerance. Chronic administration of EA restored the impaired glucose and lipid homeostasis in diet-induced obese (DIO) mice, which may be partially due to promoting GLP-1 secretion and reduced hepatic gluconeogenesis. In addition, EA suppressed appetite, reduced food intake, and gastric emptying rate, as well as promoted weight loss in the DIO mice, demonstrating that it is also an anti-obesity agent. Further, EA treatment reduced lipid absorption and promoted hepatic fatty acid oxidation, as well as reversed abnormal plasma lipid profiles in the DIO mice. Consistently, EA exerted potent anti-diabetic action in predisposed diabetic mice (db/db), and its blood glucose-lowering effect is comparable with that of liraglutide, a commercial GLP-1 receptor agonist, in blood glycemic control but is better than that of metformin, a widely used first-line anti-diabetic drug, in this overt diabetic model. Collectively, I have identified for the first time, as to the best of our knowledge, that EA could be a dual-action compound that exerts anti-diabetic effects via activation of the GLP-1 mediated metabolic pathway and suppression of hepatic gluconeogenesis, leading to effective control on food intake, body weight gain, and glycemia in T2D mice.

This study investigated the effects of exercise and dietary iron on iron status in 19-month-old female rats. Fifty-seven female Sprague-Dawley rats were randomly assigned to one of five experimental groups: baseline (BL); iron sufficient-exercise (HE); iron sufficient-sedentary (HS); moderate iron deficient- exercise (LE) and moderate iron deficient-sedentary (LS). The six-week exercise protocol involved swimming 5 days/week beginning at 10 minutes/day and ending at I hour/day by the fifth and sixth week. The results indicated a significant effect of exercise on food intake and on body weight, with higher levels of intake and body weight in the LS group compared to the exercised groups. Soleus muscle weight was significantly lower than BL in the HS, LE and LS groups. Gastrocnemius muscle weight was significantly higher in the HS than in the LE group. Cardiac weights were comparable in the1LE, LS and HE groups but significantly higher than the HS group. Cardiac citrate synthase activities were not significantly different among the groups. No significant effects of diet, activity or an interaction effect were noted on hemoglobin, serum iron and total iron binding capacity. Hematocrit concentrations demonstrated a significant effect of activity, with elevated levels in the exercised groups compared with baseline. Serum iron levels were significantly lower in the LE group than the iron sufficient groups. The TIBC levels were significantly lower in the LE group than in the baseline. Liver iron concentrations showed a significant effect of diet, with higher concentrations in the iron sufficient groups compared to the LE group. Iron concentrations in the spleen and soleus muscle were unchanged however spleen iron concentrations were significantly higher in BL than in the experimental groups. Exercise had a significant effect on the gastrocnemius muscle with lower iron concentrations in the sedentary groups than in the exercised groups. These results suggest a trend towards redistribution of iron stores as a result of exercise as evidenced by alterations in iron concentrations in some tissues and a trend towards elevated hemoglobin and hematocrit levels. Thus, dietary iron deficiency and exercise adversely affected various components of iron metabolism in the aged female rat although it was not manifested as iron deficiency. / Master of Science

Understanding the central nervous systems role in appetite regulation is crucial to cure the obesity epidemic, which is more prevalent than any disease in the United States. Central appetite regulators, known as neuropeptides, are pivotal in understanding appetite regulation. Neuropeptide Y (NPY), a 36 amino acid peptide, plays a major role in regulating the hunger signals from the brain. In all vertebrates studied, it is a strong orexigenic neurotransmitter located throughout multiple nuclei of the hypothalamus. Peripheral hormones associated with hunger are able to activate NPY neurons in the arcuate nucleus, which leads to a cascade of events that activate orexigenic neurons throughout the hypothalamus. Although extensive research has gone into understanding the role of NPY in appetite regulation, the effects of macronutrient composition of diets on NPY function have not been elucidated in non-mammalian species. This research investigates how food intake is affected by dietary macronutrient composition in broiler type chickens that are fed three varying macronutrient diets: high carbohydrate (22% CP, 3000kcal/kg) a broiler starter diet, high fat (60% ME from lard), high protein 30%CP). All diets were formulated to be isocaloric. When chicks are fed the high fat diet central NPY administration has a greater effect on feed intake compared to both the basal and high protein diet. Regardless of what diet the chick is fed from hatch, if they are switched to one of the other two diets post central administration of NPY the high fat diet stimulated feed intake for the longest duration. Although, NPY had the strongest orexigenic effect on chicks fed the high fat diet, in a choice diet situation broiler chicks chose the high protein diet, independent of central NPY administration. / Master of Science