The studies in this thesis aimed to develop and characterise a rodent model of meal feeding that would mimic aspects of human eating behaviour, leading to the overconsumption of calories and ultimately to obesity. In seeking to identify potential mechanisms that might be involved in the initiation of meals, a palatable scheduled feeding regime was utilised to induce a substantial food intake over short periods of time in rodents. This was done by providing scheduled access to a palatable diet for a 2h-period each day without imposed caloric restriction during the remainder of the day. Initially, the effects of different palatable diets were examined. Three of the four palatable diets resulted in a rapid adaptation of feeding behaviour and induced the consumption of large, binge-type meals in both Sprague Dawley rats and C57BL/6 mice. Candidate gene expression analysis by in-situ hybridisation during the two hour period leading up to scheduled feeding suggested that homeostatic neuropeptide systems in the hypothalamus did not have a major role in driving the consumption of these meals. Further characterisation of the scheduled feeding model revealed that palatable scheduled feeding does not lead to a relative hypophagic phase or an increase in pre-meal secreted gut hormones in anticipation of the scheduled meals. Interestingly, schedule-fed animals exhibited food anticipatory activity during the same period. In addition, scheduled-fed animals displayed only a mild obese phenotype but their metabolic health was adversely affected. Again using in-situ hybridisation, candidate gene expression was assessed during the scheduled feeding period itself, revealing a relationship with adiposity level but not with immediate feeding behaviour. Finally, in a ‘hypothesis-free' approach, gene expression was analysed by microarray at the point of initiation of scheduled feeding, with no apparent changes in gene expression levels. In conclusion, palatable scheduled feeding in mice and rats induces large, binge-type meals that appear not to be directly regulated by homeostatic neuropeptides in the hypothalamus. Investigations into forebrain candidate gene expression by in-situ hybridisation suggested that measuring mRNA levels might not be the optimal analytical approach to demonstrate an involvement of the reward-related signalling system. Alternative strategies for identifying meal feeding mechanisms in the palatable scheduled feeding model could focus on approaches such as neurotransmitter release.

Ghrelin is an appetite-stimulating hormone produced mainly in the stomach and duodenum. Poor ghrelin control is often caused by obesity-related hyperinsulinemia, which fails to suppress ghrelin and results in excess appetite and higher body fat storage that perpetuates even greater fat accumulation. High intensity exercise has been shown to acutely decrease plasma acylated ghrelin concentrations in healthy weight individuals. However, the evidence for how exercise affects ghrelin in obese individuals is currently lacking. PURPOSE: To compare the effects of high intensity interval exercise on acute plasma acylated ghrelin levels in obese and non-obese males. METHODS: Eighteen subjects with a mean age of 29.8 yr. (± 7.6) were assessed for body fat percent (BF%), acylated ghrelin and hunger. Subjects included 9 non- obese men (BF% mean= 13.7 ± 3.6) and 9 obese men (BF% mean = 31.7 ± 4.7) who agreed to participate in this study. Using a crossover design, participants were randomly assigned to an exercise or control condition, with each subject acting as their own control. The exercise trial consisted of participants cycling at high intensity intervals for 20 minutes (not including the 5 minute warmup and cool down) at a rate of 65% to 85% of their heart rate reserve on a cycle ergometer followed by 60 minutes of rest. The control trial consisted of 90 minutes of rest. Blood samples (3-4ml) were collected at baseline, 0.5, 1, and 1.5 hours post-intervention. Acylated ghrelin concentrations were determined from plasma. Hunger was assessed using a 10-point Likert-type scale while blood samples were being drawn. Group means for plasma ghrelin concentrations between groups were analyzed using an independent t-test. The effect of exercise on ghrelin was analyzed using paired t-test. The relationship between perceived hunger and ghrelin was assessed using Pearson correlations. RESULTS: Baseline plasma ghrelin levels were significantly higher in the non-obese group when compared to the obese group (t = 3.43, p = .036). While exercise was effective in reducing plasma acylated ghrelin levels in the non-obese group (t = 2.34, p = .047), no significant changes were found in acylated ghrelin in the obese group between baseline or any time point following the exercise intervention. CONCLUSIONS: The low resting levels of plasma ghrelin concentrations exhibited by the obese subjects, when compared to non-obese subjects, may result in long fasting periods that lead to hypoglycemia and a hyperinsulinemic response at the next eating opportunity. Furthermore, the lack of reduction in ghrelin following exercise may result in an overconsumption of energy. Both the sustained ghrelin with associated excess energy intake and the hyperinsulinemia may result in sustained or increased fat storage in obese individuals.

published_or_final_version / Paediatrics / Doctoral / Doctor of Philosophy

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Nursing Studies / Master / Master of Nursing

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No description available.

No description available.