Investigation of the physiological mechanisms regulating appetite and food intake humans.

It is generally accepted that human appetite is under multifactorial control, and that investigation of each facet implicated in appetite regulation is required to develop understanding in this area. The current research aimed to investigate subjective appetite ratings and ad libitum food intake in response to manipulated preloads, while simultaneously measuring the hormone and metabolite response and gastric emptying rate of those preloads. This tripartite approach was then used to explore the relationship between the gastrointestinal hormones GLP-1 and CCK, and appetite. Manipulated preloads differing in their carbohydrate and fat content were used to investigate the post-prandial response. Increasing the carbohydrate and energy content of a preload was shown to decrease ad libitum food intake, although there were no obvious effects on subjective appetite ratings. In addition the secretion of GLP-1, GIP, insulin and glucose were significantly increased as preload carbohydrate and energy content increased. The gastric emptying of the preload was slower as carbohydrate and energy content increased. The manipulation of preload fat and energy content showed a similar pattern of response, with decreased ad libitum energy intake and delayed gastric emptying as preload fat and energy content increased. Hormone and metabolite responses showed significant increases in CCK and GLP-1 with increasing preload fat and energy content. To investigate further the role of GLP-1 in the regulation of human appetite, appetite responses during a GLP-1 infusion were assessed against a saline control. The infusion of GLP-1 did not have a significant effect on self rated appetite or ad libitum energy intake, and was not supportive of a major role for GLP-1 as a satiety hormone in man. However GLP-1 infusion significantly delayed gastric emptying of a water load, supporting the role of GLP-1 as a regulator of gastric emptying. The role of CCK in human appetite was similarly investigated, using an infusion of the CCKA receptor antagonist loxiglumide against a saline control. Loxiglumide infusion significantly increased ad libitum energy intake, and significantly increased the rate of gastric emptying of a high energy liquid preload. The infusion was also found to significantly increase GLP-1 and insulin responses, and the increased ad libitum energy intake was observed in spite of high GLP-1 levels with loxiglumide infusion. The ad libitum test meal intake data from the manipulated preload studies showed that a small number of subjects did not adjust their intake according to preload energy intake. Thus the role of habitual exercise levels on food intake response was assessed to determine if this poor response was related to lifestyle differences. Individuals who participated in regular recreational exercise were found to better adjust ad libitum energy intake in response to manipulated preloads than those who undertook no regular recreational exercise. These data provide support a role for exercise in the regulation of food intake. Taken together these data provide evidence that the differing hormonal responses to manipulated preloads are involved in the regulation of appetite response. Investigations of the roles of GLP-1 and CCK in appetite suggest that CCK is a more potent regulator of appetite than GLP-1. The role of exercise in determining the appetite response to manipulated preloads suggests that the investigation of lifestyle differences is also of importance in the understanding of human appetite