Interactions between metabolic, cognitive and reward processes in appetite

Recent research has helped us understand the processes that lead us to prefer certain foods over others and the factors that influence how much we eat. We know that through experience we learn that some foods are very rewarding to eat and this learning influences our food choices. We also know that signals relating to the ingestion of food arising from the body (metabolic signals) modulate processes in the brain that are important for determining how much a food is desired. Food is less attractive when we have just eaten for this reason. Our food choices are also influenced by cognitive processes such as attention and memory, for example, when thinking about food we are likely to pay attention to food in the environment and may be more likely to eat. Although we know that metabolic signals and cognitive processes directly influence food reward we know very little about how these factors interact to affect eating. New evidence from our research team suggests that metabolic signals may affect food reward indirectly via modulation of higher cognitive functions. The aim of this research programme is to investigate this idea by examining the effects of specific metabolic signals on cognitive processes and food reward. This is a new approach to the study of food choice and the results will have implications for both theory and practice. Potential practical benefits will include the possibility of developing more effective interventions to help people control their food intake.

The frequency and size of meals are influenced by activity in brain circuitry that processes nutritional state signals and food reward value. Thus, consumption of food is associated with reduced activity in reward circuitry and decreased incentive value of food, which is reflected in reduced responses to appetitive stimuli in reward-related brain areas. Eating is also influenced by higher cognitive functions such as attention and memory that also affect reward processing. Recent evidence from our laboratory suggests that metabolic signals related to nutritional signals may also have indirect effects on food reward via alterations in higher cognitive functions. We have pilot data showing that eating to fullness after a natural inter-meal interval is accompanied by increased activity in the dorsolateral prefrontal cortex (dlPFC), an area that is associated with attention, memory and cognitive control. These data suggest that the termination of a usual meal is associated with changes in cognitive control mechanisms that supress intake. We have also recently reported the novel finding that the 5-HT2C receptor agonist mCPP, which is known to reduce food intake, enhances memory. Our overarching aim is to test the hypothesis that metabolic signals have effects on specific higher cognitive control functions and that these effects are related to eating behaviours via changes in reward-related responding. We will conduct three large scale experimental studies assessing the effects of intranasal insulin (study 1) the serotonin 2C agonist mCPP (Study 2) and ghrelin (Study 3) on inhibitory control, attention, memory, eating behaviour and fMRI BOLD responses. In each study the effect of drug administration will be tested in both lean and obese participants.

The results of this project will be of interest to industry, health professionals and policy makers as well as the general public. Economic and societal impacts include adding to the knowledge base on controls of eating that could later lead to improvements in health and well-being. Given the health costs associated with unhealthy eating patterns it is important to explore new avenues for improving the Nation's diet through developing comprehensive models of appetite control that open the way for thinking about new interventions and advice on nutrition. The idea that metabolic signals may affect appetite control via novel mechanisms will be of interest to both the food and pharmaceutical industry and the results could lay the groundwork for further testing of products aimed at enhancing appetite control. This will be facilitated by the involvement of the industrial partner P1vital. Wide dissemination of the results (see pathways to impact plan) will ensure that a range of stakeholders are reached and beneficiaries of this project are not be limited to those in the UK. Engagement with the public will enhance understanding of the complexities of appetite control and interactions with the public will be important for improving the quality of research and its impact. It will also ensure wide communication of the results and inspire the next generation of researchers. The work will also contribute to the development of a promising early career researcher. The named RF will be given the opportunity to develop further experimental skills and experience that will enable him to further establish himself as an up and coming research star.