Thesis (Ph. D.)--University of Notre Dame, 1941. / Lithoprinted. Bibliography: p. 145-147.

Food intake is essential to all animals. However, when energy consumption through food overtakes energy expenditure, obesity can result. Obesity has been identified as a worldwide health problem associated with diseases such as type 2 diabetes and hypertension. Thus, it is essential to find effective anti-obesity therapies. The aim of this thesis was to determine whether the histaminergic system could be pharmacologically manipulated to alter food intake and whether in particular the H3R is a suitable therapeutic target. Histamine is a central neurotransmitter that plays a major role in controlling energy balance by acting through specific hypothalamic sites. Injections of histamine receptor-1 (H1R) antagonists into the ventromedial hypothalamic nucleus (VMN) cause hyperphagia, whereas antagonism of presynaptic histamine receptor-3 (H3R) causes hypophagia, leading to the hypothesis that selective antagonists or inverse agonists might be potential treatments for obesity through their actions on central H3R. My aim was to assess the precise mode of action of histamine and H3R drugs to affect acute, appetitive behaviour. Using feeding and behavioural studies I demonstrated the acute anorexigenic actions of histamine (ICV) and the H3R inverse agonist, thioperamide (ICV or IP), in rats without disrupting the behavioural satiety sequence. In accordance with predictions, the H3R agonist, imetit (ICV or IP), increased feeding. The actions of both thioperamide and imetit were blocked by the drug proxyfan, which in our model is acting as a neutral H3R antagonist. Interestingly, both thioperamide and imetit caused anorexia in mice. C-Fos functional immunostaining revealed that systemic administration of thioperamide and imetit increased the activity of neurones in the key feeding nuclei of the hypothalamus, including the VMN. To further investigate the mode of action of histaminergic drugs, I carried out extracellular electrophysiological recordings from neurones of the rat VMN in vitro. Of the 197 VMN cells recorded, 62% were histamine-responsive, with 97% of these showing an increase in neuronal firing rates in response to histamine. The excitatory response to histamine was blocked in 90% of instances by pyrilamine, a selective H1R antagonist. Neurones that responded to histamine previously were treated also with thioperamide. 88% of these neurones also responded with an increase in firing. The effect of thioperamide was blocked in all cases by co-administrating pyrilamine, proving that H3R in the VMN are presynaptic autoreceptors, rather than heteroreceptors modulating the release of other transmitters. Imetit had an inhibitory effect on VMN neuronal firing in 86% of recorded cells. Proxyfan was able to block the changes in neuronal firing that both thioperamide and imetit caused. This suggests it is acting as a neutral H3R antagonist in both our in vivo and in vitro models. Thus, using a neutral H3R antagonist we have proven the effects imetit and thioperamide had on feeding and neuronal VMN firing were a direct result of activating a H3R and, therefore, these compounds are receptor-specific for the H3R. In conclusion, our results support a role for histaminergic receptors, including postsynaptic H1R and presynaptic H3R autoreceptors in the VMN, to modulate feeding.

No description available.

My investigation of pleasures involved in an Aristotelian temperate action starts with Aristotle’s account of health presented in Metaphysics, Physics, and his other biological works. Aristotle’s conception of health provides the theoretical backdrop in which two modes of temperate action concerning bodily pleasures involving appetite and pain are made possible. The temperate person is capable of acting temperately because the rational part of the human soul can influence appetite, and the contact between the pleasant and what is good for health allows two possible ways of action. When the pleasure of appetite is within the range of what is good for health or does not harm health, temperate people may pursue it; when the two do not match, a temperate action does not involve any bodily pleasures, and is simply the activity of the rational soul. This thesis emphasizes the second mode of temperate action, since this type of temperate action simply consists in the activity of the rational soul, specifically, acting out the deliberate decision of avoidance. / Thesis / Master of Arts (MA) / In Aristotle’s ethical theory, the virtue of temperance is related to two types of pleasures. One type is the bodily pleasures involving appetite and pain, the other is the pleasure following upon a temperate action. My examination of his conception of health reveals that, in acting temperately, temperate people experience the second type of pleasure in their abstinence from the enjoyment of the first type of pleasures.

Melanocortins play a key role in appetite regulation across species. One such melanocortin, beta-melanocyte stimulating hormone (beta-MSH) is receiving increasing attention for its anorexigenic effects. In chicks selected for low (LWS) and high (HWS) juvenile body weight, beta-MSH differentially decreased food intake and HWS chicks may be more sensitive to its effects. Both lines responded similarly to beta-MSH with decreased water intake. While whole blood glucose concentrations and ingestive and non-ingestive behaviors (sit, stand, preen, perch, deep rest, jumps, escape attempts, feed pecks, defecations, and total distance traveled) were not affected in either line, beta-MSH increased corticosterone in LWS chicks but not HWS chicks. However, despite the increase in corticosterone concentration in LWS, astressin, a corticotrophin releasing hormone (CRH) receptor antagonist, did not attenuate the effects of beta-MSH in either line suggesting that the altered stress response may not be acting via CRH receptors. When beta-MSH was co-administered with HS014, a highly selective antagonist for the melanocortin 4 receptor, only LWS responded with an attenuated response to beta-MSH suggesting that the differential response may in part be due to altered receptor affinity or binding resulting from the selection process. To investigate the roles of the hypothalamus and hindbrain in the differential food intake response, an experiment was designed where chicks were injected targeting either the lateral or 4th ventricle utilizing a novel freehand injection procedure. Chicks from both lines responded similarly to beta-MSH following both lateral and 4th ventricle injections. Together, these data suggest that alterations in the b-melanocortinergic appetite regulation system may be in part responsible for the differential body weights of the LWS and HWS lines. [Adaptations of chapters II, III, and IV have been published in Neuroscience Letters, Journal of Neuroendocrinology, and Behavioural Brain Research, respectively] / Ph. D.

The purpose of this descriptive correlational study was to examine relationships among the sensations and cognition components of perceived hunger and four contextual correlates: physiological, emotional, environmental, and established patterns. The study examined (1) relationships among the contextual factors and components of perceived hunger, (2) differences between normal weight and overweight individuals in their perception of hunger, and (3) multivariate relationships among contextual factors and perceived hunger. The convenience sample was comprised of 359 healthy adults living in western Canada. The theoretical framework for this study emerged from the global context of the eating experience, specifically the relationship between the constructs of contextual factors and hunger. Physiological context was estimated by body mass index. Instruments used to estimate the concepts, emotional context, environmental context, established patterns, sensations, and cognition were immature instruments. Reliability and validity had been assessed in a pilot study. Statistical analysis of data included descriptive statistics, Pearson Product Moment Correlation, one-way analysis of variance, and stepwise multiple regression techniques. Approximately 58 percent of the variance in the cognitive struggle component of perceived hunger, was accounted for by the intensity of the individual's negative emotions and their degree of adiposity. Other patterns were indicative of trends. The linear composite of negative emotions, environmental factors, and the immediacy component of the established patterns accounted for 22 percent of the variance in the enhancers aspect of cognition. Nineteen percent of the variance in the sensations component was accounted for by the linear composite of the immediacy component of established patterns, environmental context, degree of adiposity, and negative emotions. Both overweight and obese individual's perception of sensations denoting hunger was significantly less intense than those experienced by normal weight individuals. The obese individual's perception of cognitive struggle was significantly more intense than that experienced by underweight, normal weight, or overweight individuals. Overweight individuals experienced cognitive struggle with significantly greater intensity than did underweight individuals. Nurses in clinical settings may use the findings for assessing and formulating nursing interventions related to eating behavior.

No description available.

Obesity is a prevalent problem in modern society, which requires the upmost attention in the biomedical sciences. A leading cause of obesity related diseases is due to overeating, especially in industrialized countries. Leptin is the hormone that is secreted by fat cells responsible for communicating body nutritional status to the brain. Leptin interacts with other bodily systems such as the cognitive, digestive, neuronal, and endocrine systems. Leptin acts mainly on the Ob-Rb receptor in the arcuate nucleus of the hypothalamus and largely suppresses food intake and increases energy expenditure by activating Proopiomelanocortin and Cocaine- and amphetamine-regulated transcript (anorexigenic signals) neurons and by suppressing Neuropeptide Y and Agouti-related peptide (orexigenic signals) neurons, among other chemical signaling pathways. In both rodent and human studies, exogenous leptin administration resulted in elevated plasma leptin concentrations. When researchers tried to use leptin for weight reducing medical treatments in humans, the results show difficulty in establishing clinical efficacy. However, for diseases such as congenital leptin deficiency, obesity related leptin resistance, and lipodystrophy, medical treatments involving exogenous leptin have been relatively successful. The goal of this thesis is to give readers an understanding of leptin’s role in regulating appetite and the different leptin associated diseases. Leptin’s role is still continuing to be developed and more research is needed to fully utilize leptin for therapeutic benefit.

The fifth basic taste, ‘umami', is the flavour function elicited by amino acids like monosodium glutamate (MSG) in foods. This taste is recognized for its flavour enhancing properties but little is known about its effects on appetite and intake. Thus the experiments in this thesis aimed to understand how umami influences pleasantness, appetite stimulation, satiation and satiety using MSG, with some additional focus on its associated ribonucleotide inosine 5'-monophosphate (IMP). Chapter 2 established a bland, low glutamate control soup which was used throughout all subsequent experiments to test the effects of MSG on palatability using commercially-relevant concentrations. Chapters 3 and 4 assessed the influence of increasing palatability on rated appetite and intake of this soup with either added MSG (Chapter 3) or added sucrose (Chapter 4). No increase in hunger or intake was found after the more palatable conditions. Chapter 5 explored the relationship between MSG taste and protein regulation, assessing acute and habitual protein intake with findings indicating that high protein consumers liked high MSG concentrations more after an acute protein deprivation than sweet, salty or control flavours. Chapter 6 examined the time course of rated MSG satiety alone and in combination with either protein or carbohydrate in a preload soup and found enhanced rated satiety in MSG protein conditions. This design was extended in Chapter 7 to include an intake test after a pre-specified time of consuming the preload soup. The results indicated better compensation after MSG protein conditions but no differences in intake were found across carbohydrate or control conditions. Chapter 8 assessed MSG and IMP with or without added protein using the same design as Chapter 7 and found reductions in intake in MSG/IMP conditions. This suggests that the flavour of umami plays an important role in the regulation of appetite and intake.

The purpose of this study was to explore women’s subjective food and eating experiences from childhood through to adulthood and the ways in which these experiences either connected or disconnected them from their appetites for food and eating. The present study used a qualitative life history methodology, the goal of which is to assess individuals’ lived experiences to construct broader contextual meaning. In-depth interviews were used to investigate food and eating experiences among twelve women between ages 25 and 44, representing diverse social and cultural backgrounds as well as current and past eating problems. Participants took part in an open-ended interview, using a series of guided questions about their food and eating experiences from childhood through to adulthood. The interviews were transcribed and analyzed for themes using the constant comparison method. Two models emerged from the data in this study that described the social factors that connected and disconnected women from their appetites and eating. The Regulating Discourses Model which outlines current ways women negotiate appetite and desire through food and eating experiences, and the Socialization through Food and Eating Model which delineates socialization processes related to food and eating during women’s development. This research may be useful for counselors, health care professionals, as well as the larger community to increase awareness on ways to maintain girls’ and women’s connection to their bodily appetites and desires throughout the lifespan.