Energy balance includes energy intake and energy expenditure. Either excessive food intake or insufficient physical activity will increase the body mass and cause obesity, a worldwide health problem. In the US, more than two-thirds of people are obesity or overweight. Conversely, it is well accepted that reducing energy intake can increase the life span and the resistance to age-related diseases. MicroRNAs are highly conserved non-coding RNA molecules with a length of 21-23 nucleotides. Recent studies show that numerous microRNAs are associated with the regulation of oxidative stress, inflammation, insulin signaling, apoptosis, and angiogenesis that relate to obesity. However, the role of microRNAs in the regulation of energy balance in central nervous system remains unknown, especially within the hypothalamus, a primary site of energy balance control. In this project, microRNA, and mRNA were profiled using microarray technology. Furthermore, quantitative proteomics were used to identify differential protein levels during fasting, and in a genetically obese mouse model, Mice were given either a 24-hour fast, or ad libitum access to food. Hypothalamic RNA and microRNA samples were analyzed by microarray, using both the Affymetrix and Toray 3D mRNA and microRNA platforms. No microRNAs were found to be differentially expressed between two treatments, whereas numerous mRNAs were significantly regulated by fasting, including 7 cell cycle related genes. Hypothalamic protein samples from WT and N2KO mice treated either to ad lib feeding or 24-hour fasting were analyzed by MSE quantitative proteomics. Over 650 proteins were identified with some proteins showing significantly different abundances between or among the four groups. Between ad lib fed WT and N2KO mice, 53 proteins were differentially expressed, with some of these linked to neurodegeneration, NAD synthesis, and the citrate acid cycle (TCA). Overall, the results of this study suggest that while microRNA-mediated mechanisms are not significant modulators of hypothalamic gene expression upon a 24 hour fast, cell cycle gene expression changes represent a major contributor to the fasting response. Moreover, Nlhl2 might play an important role in the neurodegeneration and mitochondrial metabolism. / Ph. D.

Background: In 2014, there were nearly 2 billon overweight people around the world. This causes excessive costs for the society and is also a threat to the human condition. In recent time, there has been an increase of understanding the individual parts of the body composition. One method to measure body composition is using a bioelectrical impedance analyzer. The current recommendation is to measure during fasting conditions. However, there are few studies that have investigated a meal’s effect on body composition measured with bioelectrical impedance analysis, and those studies have presented varying results. If a bioelectrical impedance analyzer could be used without previous fasting, it would increase the use and utility of bioelectrical impedance analyzers. This could in turn, for example, reduce waiting lists in hospitals where bioelectrical impedance analyzers are used. Aim: The main aim of this study was to investigate a meal’s effect on body composition when measured with a bioelectrical impedance analyzer. The secondary aim was to investigate the correlation between skeletal muscle mass and hand grip strength when using a bioelectrical impedance analysis and a hand-held dynamometer respectively, during fasting conditions. Methods: In this present study, 27 subjects in the age of 21-59 years old participated. The subjects arrived at the laboratory in the morning during fasting conditions. Firstly, a bioelectrical impedance analyze and a hand grip strength test were completed. Thereafter, all subjects ate a meal containing at least 500 kcal. The following bioelectrical impedance analysis were completed 60, 90 and 120 minutes’ post meal intake. The data was then analyzed in SPSS version 20 through a paired T-test and a Pearson correlation test respectively. Results: The results showed that all body composition parameters investigated in this present study, except for minerals, not were statistically different 90 minutes after a meal intake containing at least 500 kcal, compared to the fasting condition, when measured with a bioelectrical impedance analyzer. Furthermore, a moderate correlation was found between hand grip strength and skeletal muscle mass for women. The same correlation was found weak for men. Conclusion: The results from this present study indicates that it is possible to measure body composition with a bioelectrical impedance analyzer 90 minutes’ post meal intake, except for minerals. Also, it indicates that a hand grip strength test is not a valid test for measuring skeletal muscle mass.

The purpose of the present study was to objectively verify psychological and behavioral changes in a group of identifiably susceptible patients who were treated for environmental sensitivities in a highly controlled environment. The subjects were 71 Environmental Control Unit (ECU) patient volunteers and 16 nonpatient volunteers for a total of 87. The patients were divided into a short-treatment (fasting 3-4 days) group (n = 35) and a long-treatment (fasting 5-7 days) group (n = 36). A third group, consisting of the 16 nonpatients, formed a nonpatient/no-treatment control group. All subjects were administered tests for assessment of intellectual/cognitive functioning, neurological/cerebral functioning, perceptual-motor skills, mood states, and general psychopathology.

abstract: ABSTRACT Background. College students’ modifiable health behaviors, including unhealthful eating patterns, predispose them to risk for future cardiometabolic conditions. Purpose. This novel 8-week randomized control parallel-arm study compared the effects of a daily 18-hour Time-Restricted Feeding protocol vs. an 8-hour fast on diet quality in college students. Secondary outcomes were resting morning blood pressure, biomarkers of glucose regulation, biomarkers of lipid metabolism, and anthropometric measures. Methods. Eighteen healthy college students (age = 23 ± 4 years; BMI = 23.2 ± 2.3 kg/m2; MET = 58.8 ± 32.9 min/wk) completed this study. Participants were randomized to a daily 18-hour fasting protocol (Intervention; n = 8) or a daily 8-hour fasting protocol (Control; n = 10) for eight weeks. One ‘cheat’ day was permitted each week. Outcomes were measured at weeks 0 (baseline), 4, and 8. A non-parametric Mann Whitney U test was used to compare the week 4 change from baseline between groups. Statistical significance was set at p≤0.05. Results. Diet quality (p = 0.030) and body weight (p = 0.016) improved from baseline to week 4 for the INV group in comparison to the CON group. The data suggest these improvements may be related to reductions in snacking frequency and increased breakfast consumption. Fasting blood glucose and hip circumference tended to improve for the INV group in comparison to the CON group (p = 0.091 and p = 0.100). However, saturated fat intake tended to increase in the INV group in comparison to the CON group (p = 0.064). Finally, there were no treatment differences between groups (p>0.05) for the 4-week change in total calories, dietary vitamin C, added sugars, resting systolic blood pressure, resting diastolic blood pressure, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, waist circumference, or MET. Conclusion. These data, although preliminary, suggest that the 18-hour fasting protocol was effective for improving diet quality and reducing weight in comparison to the 8-hour fasting protocol in healthy college students. Future intervention trials will need to confirm these findings and determine the long-term relevance of these improvements for health outcomes. / Dissertation/Thesis / Doctoral Dissertation Nutrition 2020

Weight loss maintenance and emotional and physical problems were investigated in subjects on a protein-sparing modified fast. Four months following a weight reduction program using the protein-sparing modified fast, twenty of the forty-two subjects were contacted. Each was asked to complete a questionnaire related to emotional and physical effects of the diet and a diet history checksheet. Each subject was weighed to determine if weight loss had been maintained. Results of the questionnaire, diet history, and blood chemistry analysis indicate that for these subjects, the modified fast may be safe and effective in reducing and maintaining weight loss over a short time period under close supervision by a physician.

Ketosis is a metabolic condition that occurs during heat stress, prolonged exercise, fasting, and in obese and diabetic individuals. The major ketone body, β-OH butyrate, affects cellular signaling pathways in a hormone-like manner through its receptor GPR109a. While physiological ketosis is often adaptive, chronic hyperketonemia may contribute to the metabolic dysfunction of diabetes. To understand how β-OH butyrate signaling affects hepatic metabolism we compared the fasting response in control and 3-hydroxy-3-methylglutaryl-CoA Synthase II (HMGCS2) knockdown mice that are unable to elevate β-OH butyrate production, and in GPR109a +/+ and -/- mice. To directly assess the response to ketone signaling we gave intraperitoneal injections of the GPR109a agonists niacin (0.8mmol/kg) and β-OH butyrate (5.7mmol/kg) to HMGCS2 knockdown mice over the final 9 hours of a 16 hour fast. Ketogenic deficient mice showed a more robust increase in hepatic carnitine palmitoyltransferase 1 (CPT1) and uncoupling protein 2 (UCP2) mRNA than control mice in response to fasting. Accordingly, niacin and β-OH butyrate administration decreased fasting CPT1 mRNA expression in knockdown mice, while fasting knockdown UCP2 mRNA and control HMGCS2 mRNA were lowered by β-OH butyrate. GPR109a knockout did not alter the hepatic response to fasting, although the effect of niacin on fasting HMGCS2 mRNA expression was dependent on GPR109a expression. While the role of GPR109a and how chronic hyperketonemia alters β-OH butyrate signaling require further study, these data suggest that endogenous β-OH butyrate signaling during a fast regulates the transcript levels of hepatic genes directly involved in its own synthesis.

A homeostase hidro-eletrolítica é controlada por informações sobre volume e a concentração dos íons dos líquidos corporais. Alterações da osmolalidade são detectadas por receptores presentes em diversas regiões do SNC, entre as quais os órgãos circunventriculares. Alterações conformacionais nestas células ativam neurônios localizados nos núcleos paraventricular (PVN) e supra-óptico (SON) do hipotálamo, que secretam ocitocina (OT) e vasopressina (AVP). A osmolalidade plasmática aumenta em conseqüência da alimentação, o que induz a secreção de OT e AVP. Os esteróides ovarianos podem influenciar o balanço de líquidos, modulando sistemas hormonais que regulam tanto o consumo quanto a excreção de água, ou agindo diretamente em neurônios ocitocinérgicos e vasopressinérgicos do hipotálamo. No entanto, esta ação não é ainda entendida. É possível que esses sistemas respondam de forma diferente às variações de estrógeno, talvez por ação direta através de receptores de estrógeno tipo em neurônios OT e AVP do PVN e SON, e por ação indireta através de receptores de estrógeno tipo em órgãos circunventriculares. O objetivo do presente trabalho foi avaliar a participação do estradiol na modulação da secreção de AVP em resposta ao estímulo osmótico induzido pela realimentação após jejum. Para tanto, foi realizada a determinação da concentração plasmática de AVP, a análise da ativação de neurônios AVP, o conteúdo protéico de ER no PVN e no SON bem como a ativação neuronal pela expressão de FOS e a expressão de ER nos órgãos circunventriculares de animais ovariectomizados tratados com estradiol ou veículo. Os resultados mostram que a realimentação após jejum de 48 horas aumenta a expressão de FOS e a expressão da proteína de ER no PVN e SON, a expressão de FOS nos órgãos circunventriculares estudados e a concentração plasmática de AVP. No entanto, não foi observada diferença significativa entre os tratamentos. Houve uma inibição da expressão de ER nos órgãos circunventriculares estudados. Aparentemente, o estradiol não participa da elaboração de uma resposta frente ao estímulo osmótico induzido pela realimentação e não interfe na ativação de neurônios AVP e na secreção desse hormônio para circulação sanguínea. / The hydroelectrolyte homeostasis is controlled by information on volume and concentration of ions in the body fluids. Osmolality changes are detected by receptors in various regions of the CNS, including the circumventricular organs. Conformational changes of these cells activate neurons located in the paraventricular (PVN) and supraoptic (SON) nucleus of the hypothalamus, which secrete oxytocin (OT) and vasopressin (AVP). Feeding increases the plasma osmolality which induces the secretion of AVP and OT. Ovarian steroids may influence the balance of fluids modulating hormonal systems that regulate both consumption and excretion of water or acting directly on oxytocinergic and vasopressinergic neurons of the hypothalamus. However, this action is not clearly understood. It is possible that these systems respond differently to the estrogen changes perhaps by direct action through estrogen receptor type in AVP and OT neurons of the PVN and SON, and by indirect action through estrogen receptor type in circumventricular organs. The objective of this study was to evaluate the participation of estrogen in the modulation of AVP secretion in response to osmotic stimulus induced by refeeding after fasting. For this purpose, we performed the determination of plasma AVP, the analysis of the activation of AVP neurons, the protein content of ER in the PVN and SON as well as activation by neuronal expression of FOS and the expression of ER in the circumventricular organs in estrogen-primed and -unprimed ovariectomized animals. The results show that refeeding after fasting for 48 hours increases the expression of FOS and ER protein in the PVN and SON, the expression of FOS in the circumventricular organs studied and plasma AVP. However, there was no significant difference between treatments with estrogen or vehicle. There was an inhibition of ER expression in the circumventricular organs studied. Apparently, estrogen does not participate in the preparation of a response to the osmotic stimulus induced by refeeding and it does not interfere in the activation of AVP neurons or the secretion of this hormone to the bloodstream.

As dietas intermitentes (IF) compreendem ciclos alternados de 24 horas de jejum e alimentação. Como os efeitos de IF sobre o balanço redox não são bem conhecidos, esse trabalho teve por objetivo avaliar os efeitos desta dieta sobre o estado redox de diferentes tecidos de ratos. Após um mês de tratamento, os fígados dos ratos em IF apresentaram um aumento de capacidade respiratória mitocondrial juntamente com níveis elevados de proteínas carboniladas. Verificou-se ainda um aumento em danos oxidativos no cérebro destes animais. IF promoveu significativa proteção contra danos oxidativos no coração, enquanto que não houve alterações no estado redox do músculo esquelético. Os efeitos metabólicos de IF também foram investigados com o intuito de compreender os mecanismos envolvidos com o menor peso e a hiperfagia promovidos por esta intervenção. Observou-se que o menor peso dos ratos submetidos à IF é consequência de um aumento em taxas metabólicas em dias de alimentação somado à oxidação lipídica aumentada durante o jejum. A hiperfagia, por sua vez, é consequencia de elevação nos níveis de neurotransmissores orexigênicos hipotalâmicos, mesmo quando estes animais estão alimentados. Os níveis do neutransmissor TRH também foram modulados por esta dieta, o que pode estar relacionado com as alterações de taxas metabólicas observadas no modelo. Concluímos, portanto, que as dietas intermitentes promovem modificações funcionais no hipotálamo que estão associadas com diferenças no peso corpóreo e no apetite. Além disso, IF afeta o balanço redox de forma tecido específica, levando a um desbalanço oxidativo no fígado e no cérebro e à proteção contra danos oxidativos no coração. / Intermittent fasting (IF) is a dietary intervention that comprises 24 hour cycles alternating ad libitum feeding and fasting. We address here the effects of IF on redox state in different tissues, which are still poorly understood. After one month on the diet, IF rats livers presented increased mitochondrial respiratory capacity along with increased levels of protein carbonyls. Surprisingly, IF animals also presented an increase in oxidative damage in the brain. Conversely, IF promoted a substantial protection against oxidative damage in the heart. No difference in redox homeostasis was observed in the skeletal muscle. We also assessed metabolic effects of IF to uncover the mechanisms involved in the lower body mass and loss of feeding control in IF rats. As measured calorimetrically, IF animals presented high metabolic rates during feeding days and increased lipid oxidation on fasting days, which explains the lower body weight. IF-induced overeating was a consequence of increased expression of hypothalamic orexigenic neurotransmitters, even on feeding days. THR levels also were changed, in parallel with the feeding-dependent alterations on metabolic rates. Overall, we find that intermittent fasting promotes functional hypothalamic alterations associated with differences in body weight and appetite. In addition, IF affects redox balance in a tissue-specific manner, leading to redox imbalance in the liver and brain, as well as protection against oxidative damage in the heart

Cross-sectional evidence associates breakfast omission with negative health outcomes. The present work aimed to examine if these cross-sectional associations have a causal component, by conducting randomised control trials in healthy humans. It was established using lean individuals that there are divergent hormonal responses to morning feeding and fasting, although increased energy intake at lunch following fasting incompletely compensated for breakfast intake. Hormonal and subjective appetite responses in the afternoon did not consistently provide evidence for increased hunger following fasting. In the same participants assigned to a 6-week free-living intervention of either 700 kcal pre 11:00 or fasting until 12:00 daily, it was found that energy intake was greater in those assigned breakfast consumption, but that physical activity was also greater than those fasting. Cardiovascular risk factors and measures of metabolic control were largely unaffected by either intervention. There was no adaptation of acute metabolic/hormonal responses to feeding following either intervention. In obese individuals, similar patterns of results were obtained for the hormonal and metabolic responses to acute feeding and fasting, but with no compensation for breakfast intake at lunch. Results from the free-living intervention demonstrated no difference in energy intake between groups or physical activity over the entire day, but greater energy expenditure during the morning in those consuming breakfast. Markers of cardiovascular health and metabolic control were generally not differently affected by either intervention. Neither intervention caused adaptation of the acute hormonal and metabolic responses to feeding. In summary, acute morning fasting does not cause complete compensation for breakfast intake at lunch, or result in greater hunger throughout the afternoon. Daily morning fasting does not affect acute responses to feeding or cause increased energy intake or weight gain relative to self-selected breakfast consumption, but seems to limit physical activity in lean, and to a lesser extent, in obese individuals.

<p>The aim of this study was to investigate for how long patients fast before thoracic surgery, plastic surgery and ear, nose and throat surgery, at the University hospital of  Uppsala, and what knowledge patients have about fasting and how they get affected by it. 30 patients were interviewed, 10 patients at each ward, according to a questionnaire. Data processing was performed with SPSS. There was no difference in fasting time for solids between the wards but the mean fasting time was 14 hours. In the thoracic ward patients fasted from liquids considerably longer than in the other wards. The mean fasting time in the thoracic ward was 12 hours compared to six hours in the ear, nose and throat ward and five hours in the plastic surgery ward. Only 27 % (8/30) of the patients knew the reason for fasting before anesthesia. Patients experienced significantly more thirst, nausea and hunger after than before surgery but no difference was seen between men and women. Patients from the thoracic surgery ward experienced more nausea before surgery than the others. The conclusion is that the compliance to the recommendations for preoperative fasting is insufficient and doesn´t comply to the patients needs.</p>