Multiple gut hormones are involved in the regulation of food intake. Secretin (SCT), a classical gut hormone, is released into the circulation from the duodenal S-cells when acidic chyme enters the duodenum and performs the major functions of delaying gastric emptying, stimulating fluid secretion from pancreas and liver to optimize the digestion process. In recent years, SCT and its receptor (SCTR) have been identified in discrete nuclei of the hypothalamus, including the paraventricular nucleus (PVN) and the arcuate nucleus (Arc). The occurrence of SCT and SCTR in the brain regions that are engaged in regulating body energy homeostasis and the release pattern of SCT after meals support a functional role of SCT in appetite control. In this study, the effect of SCT on feeding behavior was investigated using wild-type (wt), SCT?/?, and SCT receptor-deficient (SCTR?/?) mice. We found that both central and peripheral administration of SCT could reduce food intake in wt but not in SCTR?/?mice. SCT induce Fos expression in the PVN and Arc, suggesting the activation of hypothalamic feeding centers by this peptide. Consistent with this notion, SCT was found to increase proopiomelanocortin (POMC), but reduce agouti-related protein (AgRP) transcripts in the Arc, and augment thyrotropin-releasing hormone (TRH) and melanocortin-4 receptor (MC4R) mRNA expression in the PVN. In addition, pretreatment with SHU9119, an antagonist for MC4R, abolished the anorexia induced by SCT, suggesting that SCT may inhibit food intake via a melanocortin-dependent pathway. Gut hormones signals the brain to modulate the feeding behavior via the vagal afferent nerve, bloodstream or both. Here we showed that peripheral SCT-induced anorexia was attenuated in mice with subdiaphragmatic vagotomy, capsaicin treatment and bilateral midbrain transections. In summary, our data identify peripheral SCT as an anorectic peptide exerting its action via the melanocortin system and the vagal afferent contributes a major route in mediating the inhibitory effect of peripheral SCT on food intake. The present findings advance our understanding of the role of gut hormones in the regulation of appetite. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

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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

Learning processes play a major role in controlling intake of food. Through repeated experiences an animal acquires the ability to predict the postingestive effects of a particular food (i.e., of its nutrients and energy) from its sensory characteristics. What is unclear from the literature, however, is whether an animal can anticipate the duration of subsequent food deprivation from predictive sensory qualities of a food, and hence increase the amount eaten of that cueing food. Therefore, the aim of this work was to investigate the characteristics of this under-researched type of learning, i.e., anticipatory eating, using laboratory rats trained on two lengths of fasting (short: 2-3 h, long: 8-10 h). The main findings were as follows. 1) Anticipatory eating is learnt when a choice is given between protein- and carbohydrate-rich foods as well as on a single balanced test food. 2) The learnt extra intake of food is instrumental to preventing the return of hunger, removal of which negative reinforcement extinguishes the response. 3) The resulting return of hunger induces re-learning of anticipatory eating. 4) During the training sessions, learning of anticipatory eating competes with classical conditioning of sensory preference. Conditioning of preference is likely to be stronger with the shorter than with the longer length of fasting. Therefore, the difference between intakes before the long and the short fast at each trial is the summed result of these two mechanisms of acquired increase in intake. While preference conditioning usually reaches a maximum rapidly, depletion-avoidance increases for as long as has been tested, with interruptions of rapid self-extinction and re-learning, This self-extinction contributes to the homeostatic character of this learning. 5) High-fat maintenance diet attenuates the learning of anticipatory eating. Overall, the findings provided robust evidence that eating in rats can be controlled by instrumental learning reinforced by hunger. Accordingly, the design of an experiment on such instrumental control of eating in human subjects is proposed to conclude this thesis.

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