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Title: Behavioural and neural responses to the consumption of palatable, high-sugar food in rats
Author: Hume, Catherine Ann
ISNI:       0000 0004 7232 2551
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2017
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A complex system exists to monitor the body’s energy status and regulate food intake and energy expenditure to maintain a constant body weight. However, this homeostatic system is not the sole system regulating appetite. The hedonic system comprised of the mesolimbic reward pathway influences motivation to eat and acts alongside the homeostatic system to control feeding behaviours. It is often assumed that the hedonic system promotes the consumption of palatable, energy-dense foods and this can disrupt homeostatic mechanisms regulating food intake, resulting in energy overconsumption and weight gain in the long term. Yet, it is unclear to what extent the homeostatic system can defend body weight in an environment rich in palatable, energy-dense foods. I hypothesised that the homeostatic system compensates for the energy in palatable foods by reducing subsequent energy consumption, defined as homeostatic caloric compensation. I investigated homeostatic caloric compensation in a rat model of restricted palatable, high-sugar food access. Rats were schedule-fed moderate amounts of sweetened condensed milk (SCM) daily in addition to ad lib bland diet access. Both male and female rats calorically compensated for the energy consumed from moderate amounts of SCM through a robust and accurate reduction in energy consumed from bland diet, resulting in no short-term changes in body weight gain. However, homeostatic responses were limited as male rats were unable to fully calorically compensate for the scheduled-feeding of large amounts of SCM, an apparent loss of homeostatic control. It was not investigated whether female rats are also unable to fully calorically compensate for large amounts of SCM. It is possible that male rats consume these large amounts of SCM due to hedonic drive but continue to eat bland diet to acquire nutrients that are not present in SCM. To determine whether male rats defend bland diet consumption due to nutrient requirements, rats were schedule-fed large amounts of SCM enriched with protein or fibre. However, male rats did not fully calorically compensate for the energy in large amounts of SCM when enriched with protein or fibre. Overall, these findings demonstrate that the homeostatic system is able to respond to the hedonic consumption of palatable food through caloric compensatory mechanisms to defend body weight. However, it appears that the homeostatic system is unable to effectively respond to excessive hedonic palatable food consumption through caloric compensation alone. To shed light on what homeostatic mechanisms may underlie this compensatory behaviour, I used expression of the immediate early gene c-Fos to investigate neuronal activity following the scheduled-feeding of moderate amounts of SCM in male rats. c-Fos expression was increased in the ventral tegmental area of the mesolimbic reward pathway and in the lateral hypothalamus. The lateral hypothalamus has been proposed to act as an interface between homeostatic and hedonic systems. Therefore, in response to the hedonic consumption of palatable food, the homeostatic system and reward pathway may interact. Additionally, c-Fos expression was increased in satiety mediating brain regions of the homeostatic system, including the nucleus of the solitary tract and dorsomedial hypothalamus. This suggests that the homeostatic system may compensate for the energy in the palatable food by reducing subsequent food intake through inducing satiety. Furthermore, following the consumption of SCM, c-Fos expression was increased in magnocellular oxytocin neurons of the hypothalamic supraoptic and paraventricular nucleus. I demonstrated that the oxytocin system was activated by gut-brain signalling potentially involving the nucleus of the solitary tract. Therefore, the oxytocin system may be involved in homeostatic compensatory mechanisms triggered in response to the hedonic consumption of SCM, as part of a pathway mediating satiety. Moreover, I showed that c-Fos expression was also increased in the hypothalamic supramammillary nucleus (SuM) following the consumption of SCM. It has been previously shown that the SuM is involved in reward-related motivated behaviours and was recently implicated in the motivation to acquire and consume palatable food rewards. I also demonstrated that c-Fos expression in the SuM might be specific to the motivated consumption of palatable food, consistent with the SuM being involved in reward-related motivated behaviours. Furthermore, there is additional evidence from these studies that the SuM may functionally communicate with brain regions in the homeostatic and hedonic systems, including the lateral hypothalamus, dorsomedial hypothalamus and ventral tegmental area. Finally, I explored whether the gut-secreted orexigenic hormone ghrelin activates the SuM, as ghrelin may act at the SuM to influence feeding motivation. However, systemic ghrelin administration did not influence SuM c-Fos expression. As the SuM is activated following the consumption of SCM and may act as an interface between the homeostatic and hedonic systems, it is possible that the SuM could be a key component in the regulation of hedonic feeding. Using a rat model, I have shown that homeostatic compensatory mechanisms are triggered in response to the hedonic consumption of palatable, high-sugar food to regulate energy intake. This response is likely to involve homeostatic satiety mechanisms and interactions between multiple brain regions involved in the homeostatic and hedonic control of food intake. Overall, these findings shed light on how the homeostatic system responds to hedonic energy consumption and highlights specific brain regions that may be involved in hedonic feeding or homeostatic compensatory responses.
Supervisor: Menzies, John ; Leng, Gareth Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: calorie intake ; homeostatic system ; rat model ; reward system ; supramammillary nucleus ; oxytocin