Targeting mechanisms of hunger and satiety, and the food-gut-brain axis, in the fight against obesity
Obesityis a major public health problem across the developed and developing world. Fundamentally, overweight and obesity is the consequence of calories ingested as food and drink exceeding those that are expended through metabolism, thermogenesis and activity. Excess calories are stored as body fat (adipose tissue). Accumulation of excess body fat is associated with metabolic diseases such as type II diabetes and cardiovascular disease that have a major impact on longevity and quality of life. Although a number of drugs have reached the market for the treatment of obesity, most of these have subsequently been withdrawn due to the emergence of unacceptable side effects. This has provided additional impetus to attempts to develop dietary strategies for the obesogenic environment, and specifically for a food solution to address the issue of over-consumption of calories and the consequences of this.
Full4Health (‘Understanding food-gut-brain mechanisms across the lifespan in the regulation of hunger and satiety for health’), is a €9 million EU Framework 7 project which brings together 19 multidisciplinary academic and industry collaborators from across Europe. The project will investigate mechanisms of hunger, satiety and feeding behaviour, and how these change across the life course, effects of dietary components and food structure on these processes, and their possible exploitation in addressing obesity, chronic disease and under-nutrition.
- Dietary interventions in human volunteers tend to be focussed on a specific population group, most frequently middle-aged overweight males. However, this group may not be representative of responses across the wider population where energy balance issues are important. We need to understand how responses to food, gut-brain signals, and their integration, differ across key age groups, i.e. children, adolescents, and the elderly.
- Quite a lot is known about gut-brain signalling in satiety and energy balance, but comparatively little about the modulatory role of food on these signals, and the potential of attributes of food to contribute to reduced caloric intake.
- Research on gut-brain signalling has tended to focus on the hypothalamus (the energy balance centre) and to overlook other important brain structures with integratory capability, in particular the hindbrain, where nervous and other signals from the gut converge.
The Full4Health project will integrate investigation of human volunteers and laboratory animals with emphasis on neuronal, hormonal, molecular, physiological, psychological and behavioural responses to food at different stages of the life course. The main human dietary intervention will compare, for the first time in a single study, responses to food in 4 age groups (children, adolescents, adults and the elderly), in males and females, and in lean and overweight. Physiological and psychological responses to food may change as we develop and age, with impact on food choices and preferences. For example, it is unknown to what extent the release of gut peptide hormones which are involved in meal-processing, but which also signal satiety to the brain, is developmentally regulated. This may be a critical issue in the battle against food intake-related chronic disease, most commonly driven by over-consumption, but also in consideration of relative under-nutrition in the elderly and clinically compromised. The Full4Health project will examine the interaction of food and dietary components with the gastrointestinal tract, and will characterise the role of gut endocrine secretions, the vagus nerve, and hindbrain, hypothalamic and forebrain structures in signalling and integration of hunger and satiety. We will also apply imaging and other cutting edge technologies in both humans and rodents to answer critical research questions at different levels of the food-gut-brain axis.
Strengthened understanding of the mechanisms of hunger and satiety, and the potential to manipulate these mechanisms through the diet has direct relevance to any strategy to prevent obesity and overweight, since these conditions are primarily driven by over-consumption of calories. The behavioural, psychological and mechanistic data generated following the stratification of the general population into age groups will also relate to policy strategies being pursued to promote healthier childhood and healthy ageing, key issues in view of the alarming progress of childhood obesity and the projected national demographic. Additionally, there is potential to grow the food and drink sector by developing diets, foods or supplements that exploit the role of food in the food-gut-brain axis to promote healthier lives.