Title page, contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / The overall objective of the studies that comprise this thesis is to compare the effect of various dietary proteins and carbohydrates on acute postprandial changes in appetite sensations, ad libitum energy intake and associated regulatory hormones in overweight/obese adults. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289323 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2007

Title page, contents and abstract only. The complete thesis in print form is available from the University of Adelaide Library. / The overall objective of the studies that comprise this thesis is to compare the effect of various dietary proteins and carbohydrates on acute postprandial changes in appetite sensations, ad libitum energy intake and associated regulatory hormones in overweight/obese adults. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289323 / Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 2007

Thesis (Ph.D.)--University of Wollongong, 2004. / Includes appendices. Typescript. Includes bibliographical references: leaf 154-184.

Thesis (Ph. D.)--School of Education. University of Missouri--Kansas City, 2007. / "A dissertation in counseling psychology." Advisor: Johanna Nilsson. Typescript. Vita. Title from "catalog record" of the print edition Description based on contents viewed July 30, 2008. Includes bibliographical references (leaves 83-104). Online version of the print edition.

Thesis (Ph.D.) -- University of Rhode Island, 2008. / Typescript. Includes bibliographical references (leaves 227-239).

Thesis (Honors)--College of William and Mary, 2010. / Includes bibliographical references (leaves 34-36). Also available online.

Rising prevalence of child and adolescent obesity worldwide poses a threat to the future health and wellbeing of individuals. A better understanding of the mechanisms involved in the regulation of energy balance and therefore energy intake should help devise dietary strategies conducive to the maintenance of a healthy bodyweight during growth. Indeed, eating habits established during childhood are powerful determinants of future food preferences and choices in adulthood. Appetite for food and calorie-containing drinks is an important driver of energy intake and is modulated by a variety of environmental, psychological and metabolic factors. For instance, macronutrient manipulation and particularly increasing the protein content of meals at the expense of carbohydrates has been previously shown to reduce appetite in adults. Less research has been carried out in children due to methodological limitations. The first study described in this thesis sought to establish whether salivary sampling could be a non-invasive alternative to intra-venous blood sampling for the quantification of an appetite inducing peptide called ghrelin. Chapter 4 describes the dietary habits of a cohort of children (8-10 years old) and adolescents (13-17 years old) with a specific focus on sugar consumption and a comparison of key dietary characteristics with the Scottish Dietary Goals and with data from national dietary surveillance programmes. Subsequently, chapter 5 assesses the effect of protein content and portion size of dairy breakfast drinks in children and adolescents on appetite and caloric intake at an ad libitum snack buffet in a randomised crossover design study. Differences between age groups, nutritional status and genders were examined. Chapter 6 examines the correlations between performance at cognitive tests of executive function and ad libitum snack intake and chapter 7 presents new avenues of research into appetite in children and adolescents.

Introduction: Appetite is often impaired in patients with gastrointestinal inflammation. Up to 75% of hospitalised Crohn's disease (CD) patients are malnourished. Recent animal research has suggested that immune mediated upregulation of enteroendocrine cell (EEC) activity plays a mechanistic role in the appetite and feeding disturbance observed during gut inflammation. The role of EEC in producing factors regulating satiety and intestinal growth is well recognised but work on their use as therapeutic targets or agents in inflammatory bowel disease (IBD) is still in its infancy. EEC peptide dynamics are further controlled through dipeptidyl peptidase (DP4) protease metabolism but no data are yet available on its expression in IBD. My aim is to understand the roles of EEC in appetite control and the maintenance of gut mucosal integrity in intestinal inflammation. Methodology: Patients with CD and healthy controls were studied. Symptoms were assessed using visual analogue scores (VAS). Gut hormone responses to a test meal were studied using a multiplex-ELISA technique, and correlated to symptoms. At the tissue level, EEC markers and transcription factors were quantified using immunohistochemistry, quantitative polymerase chain reaction (qPCR) and western blotting techniques. The same techniques were used to study DP4 expression. The effects of glucagon-like peptide-2 (GLP-2) on a gut model of the epithelial barrier were studied by measuring the transepithelial electrical resistance (TEER) across GLP-2 exposed Caco-2 cell monolayers after cytokine exposure. Tight junction protein expression in naïve and GLP-2 exposed cells was quantified by western blotting. Main Results: CD patients with active inflammation displayed a significant reduction in appetite. At the tissue level, GLP-1 and chromogranin A (CgA) were significantly upregulated. At the mRNA level significant increased expression was noted for CgA, glucagon-like peptide-1 (GLP-1), ubiquitination factor 4a and neurogenin 3. At the plasma level, total polypeptide YY (PYY) was increased. A significant correlation was seen between postprandial PYY responses and symptoms of nausea and bloating. Ghrelin, was 3-fold higher in the CD group compared to controls, and showed a reversed postprandial response with a significant correlation with the CD activity index (CDAI). Protein DP4 expression was significantly decreased at the tissue and plasma level in CD. GLP-2 increased tight junction protein expression in Caco-2 cells and maintained stable TEER and tight junction protein expression after cytokine exposure. Conclusions: The data presented are compatible with a potential role of EEC in appetite dysregulation in intestinal inflammation. An enhanced EEC response to food intake may directly affect appetite in such patients through increased gut-brain signalling. These may present tractable therapeutic targets. The decrease in mucosal DP4 expression in CD may make bioactive GLP-2 more available in the affected gut, hence improving gut mucosal integrity in intestinal inflammation. This pilot work has shown that GLP-2 has a role in maintaining gut mucosal integrity in intestinal inflammation through a positive effect on tight junction protein expression.

The taste of sugar is one of the most basic sensory percepts for humans and other animals. Remarkably, animals can develop a strong preference for sugar even if they lack a functional sweet taste receptor, pointing to a detection mechanism independent of the sense of taste. Here, I demonstrate that a specific population of neurons in the brainstem is activated via the vagus nerve to create preference for sugar. These neurons are stimulated in response to sugar but not to artificial sweeteners, and are activated by direct delivery of sugar to the gut. By functional imaging of vagal neurons activated by intestinal delivery of glucose, we molecularly identified the glucose-specific transducer, SGLT1, in the gut. Next, I engineered animals where synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioral preference for sugar. Moreover, I demonstrated that these sugar preference neurons are genetically marked by enriched expression of the gene Penk, and that hijacking this circuit with a designer drug can condition preferences to initially non-preferred stimuli. These findings uncover a gut-brain circuit mediating sugar’s highly appetitive effects. Intriguingly, I discovered that dietary fat is also sensed via a post-ingestive gut-to-brain pathway, and engages the same preference-creating brainstem circuit as sugar. My results unveil an elegant convergent system where sugar and fat, which are likely sensed separately by specific gut transducers, share a unified gut-brain preference circuit for reinforcing their consumption. In the bigger picture, my findings suggest that it may be possible to develop a new class of chemicals that target the gut-brain preference axis to moderate the cravings for sugar and fat.

Intraperitoneal administration of cyclophosphamide 100 mg/kg and 200 mg/kg significantly lowered plasma sodium and significantly increased plasma potassium but did not result in saline preference in a strain of wild-derived house mice given a choice between water and saline (0.15M) to drink. Deoxycorticosterone acetate treatment in dosages up to 1.5 mg for four days also failed to increase salt intake. The data suggest a possible absence of a sodium appetite mechanism in this species.