Understanding how appetite is regulated, via exogenous or endogenous factors, is essential to animal agriculture in order to maximize production capabilities, as well as in human medicine to generate ways to treat conditions such as eating disorders or obesity. The aim of this thesis was to evaluate the effects of ferulic acid (FA), an exogenous factor found within plant cells, and oxyntomodulin (OXM), an endogenous hormone generated in the gastrointestinal tract, on food intake in avian models, as well as elucidate the hypothalamic mechanisms responsible. In broiler chicks (Gallus gallus), FA administered peripherally (IP) resulted in a transient yet potent reduction of food intake. A behavior analysis revealed that FA-treated chicks defecated fewer times than control birds. Within the arcuate nucleus (ARC) there was an increase in c-Fos immunoreactivity, indicating neuronal activation, in FA-treated chicks. Within the hypothalamus, there was a decrease in mRNA abundance of galanin, ghrelin, melanocortin receptor 3, and pro-opiomelanocortin (POMC), however within the ARC there was a decrease in POMC and an increase in c-Fos mRNA after FA treatment. OXM, a proglucagon-derived peptide produced in the gastrointestinal tract, administered intracerebroventricularly (ICV) or IP in Japanese quail (Coturnix japonica), resulted in a decrease in food intake for 3 hours post-injection. There was an increase in c-Fos immunoreactivity within the ARC as well as the dorsomedial nucleus (DMN) in quail ICV injected with OXM. In conclusion, these novel data provide insights on the similarities and differences between factors that can affect appetite regulation via anorexigenic effects. / Master of Science / Exogenous and endogenous factors affect appetite regulation. Exogenous factors originate in feed components, additives, and other environmental factors that can affect bodily functions but are derived from an external source. Endogenous factors are made within the body, such as hormones and neurotransmitters, usually in response to a stimulus, and serve to communicate signals both locally and distantly in the body. Ferulic acid (FA), a natural exogenous factor originating within plant cells, is found in commonly consumed plant-based foods. When administered peripherally into broiler chicks (meat-type birds), FA caused a direct and potent, yet quickly diminishing, decrease in food intake via activation of cells within the hypothalamus, the region of the brain that is responsible for appetite regulation. Oxyntomodulin (OXM), an endogenous peptide hormone generated within the gastrointestinal tract in response to the digestion of nutrients, is known to decrease food intake in humans, rodents, and the broiler chick. However, its effects in Japanese quail, a model closer to a "wild-type" bird, are unknown. Quail injected peripherally (outside the brain) or intracerebroventricularly (ICV; into lateral ventricle of brain) with OXM showed a reduction in food intake that was more persistent than FA's effects with the effects also mediated via activation within the hypothalamus, although through slightly different molecular mechanisms. Understanding different factors that can regulate appetite in animals is necessary for agricultural applications to maximize production and improve health and welfare, as well as in humans to elucidate methods to treat appetite-related conditions, such as eating disorders and obesity.

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Övervikt och fetma sprider sig likt en epidemi över världen. Omkring 1,9 miljarder vuxna varöverviktiga år 2014 och av dessa klassificerades 600 miljoner som feta. Forskning kring fetmas uppkomst och nya former av behandlingsalternativ pågår. En viktig faktor för uppkomst av övervikt är aptitreglering, där t.ex. Peptide tyrosine tyrosine (PYY), Oxyntomodulin (OXM) och Glucosedependent insulinotropic polypeptide (GIP) har betydelse. En litteraturstudie genomfördes där totalt nio originalartiklar från PubMed utvärderades. Syftet var att undersöka om det finns något värde i att mäta dessa hormon postprandialt. Finns det någon skillnad mellan normalviktiga, överviktiga och obesa och finns det någon skillnad mellan individer med typ 2-diabetes mellitus (T2DM) och friska individer? Finns det någon pålitlig analysmetod? Samtliga studier var måltidsstudier där olika näringsämnens påverkan på den postprandiala responsen undersöktes. Peptide tyrosine tyrosine ochGlucose-dependent insulinotropic polypeptide mättes i sex resp. fem av artiklarna och OXM mättes ien artikel. Protein, fett och kolhydrater ger en postprandial respons på PYY och GIP. Responsen av PYY var starkast efter stimuli från fett och protein. Fett tycks ge starkast respons på GIP. Fastevärden av PYY och GIP var inte olika hos normalviktiga och överviktiga i de studier som undersöktes. Det fanns en signifikant skillnad (p=0,01) mellan normalviktiga och överviktiga tonårsflickor av den postprandiala utsöndringen av PYY efter fettrik måltid, där de obesa flickorna hade lägre procentuell ändring jämfört med de normalviktiga. Pålitliga analysmetoder vid koncentrationsbestämning av dessa tre hormon i plasma är Radioimmunoassay (RIA) och Enzyme-linked immunosorbent assay (ELISA).

Bypass or resection of the stomach and oesophagus, has long been recognised to result in profound changes in the handling of ingested nutrients. This results in significant morbidity after radical surgery for oesophago-gastric cancer, in particular post-prandial hypoglycaemia, altered appetite, early satiety and noxious post-prandial symptoms. By profiling and challenging the gut hormone axis in healthy volunteers and patients who had undergone total or subtotal gastrectomy, or oesophagectomy, this thesis explores the possible causative mechanisms for the challenges faced by this patient population. In the surgical groups, an oral glucose tolerance test (OGTT) resulted in enhanced secretion of satiety and incretin gut hormones (GLP-1, GIP, PYY) and insulin, followed by hypoglycaemia in a cohort of patients. Continuous glucose monitoring of gastrectomy participants over two weeks of normal lifestyle identified an increased incidence of day and night time hypoglycaemia. RNAseq and mass spectrometry based peptidomics of human and murine enteroendocrine cells in the pre- and post-operative populations revealed no significant change in the underlying cellular pathways for nutrient sensing and gut hormone secretion, indicating that the altered hormone secretion is primarily driven by accelerated nutrient transit, rather than adaptive changes in the gut. Finally, specific blockade of the GLP-1 receptor in post-gastrectomy patients using Exendin 9-39 normalised insulin secretion and prevented reactive hypoglycaemia after an OGTT. In conclusion, profound changes in gut hormone secretion as a result of enhanced nutrient transit after foregut surgery likely underlie the early and late post-prandial symptoms seen in this group, and therapies specifically targeting the gut hormone axis, and GLP-1 in particular, could be the first targeted treatments for post-gastrectomy syndromes.