How the gut and brain regulate feelings of hunger and satiety Physiological, psychological and behavioural responses to food choices, and our dietary preferences, change as we develop and age. This is a critical issue in the battle against the food intake-related chronic diseases of overconsumption in the general population and undernutrition in the elderly and chronically sick patients. Health © Choreograph, Thinkstock The EU provided funding for a multidisciplinary European collaboration, the project FULL4HEALTH (Understanding food-gut-brain mechanisms across the lifespan in the regulation of hunger and satiety for health). Its purpose was to investigate mechanisms of hunger, satiety and feeding behaviour, effects of diet on these processes, and their application to obesity, chronic disease and undernutrition. Newly developed rodent studies were used to investigate the early developmental programming of the food-gut-brain axis, the signalling that takes place between the gut and the brain. In addition, studies were conducted into multiple feedback signalling interactions and inflammation-induced anorexia. Researchers also examined the protein leverage hypothesis (PLH) in the context of energy intake and macronutrient effects. The PLH proposes that consumption of a diet with a low ratio of protein to fat and carbohydrate drives excess energy intake, promoting obesity. In the current study, a high-protein diet induced undereating, but there was no protein leverage effect of low protein. The central processing/nutrient sensing study resulted in a better understanding of the mechanisms underlying both over- and undereating. The role of so-called obesity genes (FTO and Tmem18) was investigated by a combination of high-throughput assays, cell culture and transgenic manipulation. In a breakthrough in understanding individual variability, researchers defined population groups that respond differently to exercise-induced changes in body fat, indicating differences in energy compensation. This information was used as the basis for public health messages concerning the importance of exercise in improving appetite control and metabolic health independent of changes in body composition. It also showed that gender was not a barrier to exercising for improvements in body composition. At a mechanistic level, scientists showed that the gut hormone ghrelin is required for normal development of brain energy balance circuits in very early life. However, ghrelin function is inhibited by neonatal overnutrition. As large numbers of overweight or obese women are entering pregnancy and childhood obesity is now at epidemic levels, new therapeutic opportunities need to be developed to address the metabolic abnormalities associated with early-life overnutrition. FULL4HEALTH's investigation into the mechanisms underlying hunger, satiety and feeding behaviour and the effects of diet on these processes will help to address the challenges of obesity, chronic disease and undernutrition in individuals. Keywords Undernutrition, FULL4HEALTH, hunger, satiety, diet, ghrelin
