Regulation of food intake : a focus on ghrelin : regulatie van voedselinname : een focus op phreline

The objective of this thesis was to gain insight into the mechanisms of food intake regulation in order to facilitate the design of foods that could help to regulate energy intake. The focus of this thesis was on the recently discovered gastric hormone ghrelin, since the first available data on ghrelin suggested that it is the most potent hunger signal, known so far. Several intervention studies were initiated to investigate the role of ghrelin in food intake regulation. Firstly, the association between (changes in) ghrelin concentrations and appetite was investigated. Ghrelin concentrations were positively associated with subjective appetite scores, supporting the role of ghrelin as a hunger signal. Furthermore, there was an inverse association between the decrease in ghrelin concentrations following a meal and the spontaneous time interval between two meals (the intermeal interval, a measure of meal initiation), in normal weight subjects (r = -0.54, p < 0.05), but not in obese subjects (r = 0.08, p = 0.72). This association suggests that stronger suppression of ghrelin concentrations, postpones initiation of the next meal. However, ghrelin concentrations were not related to the amount of energy consumed during the next meal. Secondly, the effects of energy content and meal composition on the postprandial ghrelin response were investigated. It was shown that the postprandial ghrelin response to a carbohydrate enriched meal is dependent on the amount of carbohydrate and is unaffected by intake of the same volume of water. In contrast to other investigations, it was shown that a high protein meal more effectively (± 45%) decreased ghrelin concentrations than an isocaloric high carbohydrate meal (p < 0.01). Since the source of protein used differed from the other investigations, it was hypothesized that the effect of protein on the ghrelin response may be dependent on its composition. Ghrelin concentrations following a meal were strongly inversely associated with the gastric emptying rate, suggesting that ghrelin may require post gastric feedback (i.e. feedback from other factors that are released when food has entered the intestine). This feedback may be provided by insulin and GIP (glucose-dependent insulinotropic peptide), whereas concentrations of both factors were inversely associated with ghrelin concentrations. The association between ghrelin and GIP being the strongest (GIP: r -0.70; insulin: r -0.50). Ghrelin concentrations were also associated with cholecystokinin (CCK) concentrations, although not consistently over all treatments. Finally, also the role of ghrelin in the restoration of energy balance following energy restriction was investigated. However, neither 2 nor 3 days of 64%energy restriction significantly increased fasting ghrelin concentrations in normal-weight men. In obese men, ghrelin concentrations increased approximately 8% after 3 days of severe energy restriction. Changes in fasting ghrelin concentrations during energy restriction, were not associated with subsequent ad libitum food intake (r = 0.22; p = 0.21), suggesting that ghrelin does not act as a hunger signal during short-term energy restriction. In conclusion, ghrelin concentrations were associated with subjective measures of appetite and with the intermeal interval, but not with ad libitum food intake. Therefore, it is concluded that ghrelin is a hunger signal that is not involved in the determination of meal size (satiation), but that appears to be involved in the regulation of meal initiation (satiety) in normal weight men. Furthermore, ghrelin concentrations were associated with the gastric emptying rate, supporting the hypothesis that post gastric feedback is required. This feedback may be provided by GIP and other regulators of food intake, such as insulin, CCK and PYY. The postprandial ghrelin response is dependent on the energy content of the food consumed and on the type and composition of the macronutrients. Foods that contain for example dairy proteins may effectively suppress ghrelin concentrations for a longer period. These foods may then be used to postpone meal initiation, and may contribute to the prevention and treatment of overweight and obesity.