Resolving a novel brain circuit controlling appetite and body weight

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Here is a startling statistic - more than half the people in the UK are overweight or obese. This is a relatively recent epidemic that is getting worse. Excess body fat primarily results from eating more food than the body requires, calories that are then stored as fat. My research is aimed at understanding what makes us hungry and full and how we can use this information to develop new medications to treat obesity. My second aim is to provide an understanding of obesity that might offer novel strategies for future treatments. According to Dame Sally Davies, Chief Medical Officer for England, obesity is the biggest threat to health and the health of future generations. Obesity increases the risk of developing major illnesses such as type 2 diabetes, cardiovascular disease, cancer and numerous other conditions and it is associated with a reduction in lifespan by approximately 8 years. The objectives of my proposal therefore address a critical health challenge.Dieting should work, but it is not having an impact on the weight and health of the nation; 95% of people who lose weight gain it back. What is needed are multiple approaches to combat this widespread epidemic and my research is focused on the development of new medications. Surprisingly, it is the brain that rules our appetite. Key regions of the brain are responsible for receiving and processing meal information to maintain the equilibrium between hunger and fullness, and to achieve this, specialized nerve cells are wired together in mind boggling networks within our brain. Following a meal, the gut sends chemical messengers into these networks about how much food has been eaten. These messengers activate particular cells in the brain that signal to other brain regions to trigger a decision about whether we have had enough food. The goal of my research is to understand this cross-talk and to decode how hunger and satiety information is passed on between different regions of the brain. I study a brain region called the nucleus of the solitary tract (NTS) because this region acts as a gateway between the gut and the brain, integrating meal-related information and funneling it to the right brain regions so a decision can be made.What happens if more food than the body requires is regularly consumed? Not unlike tolerance to alcohol or a medication, it is possible that the NTS develops a kind of tolerance to nutrient signals and it takes more food for the brain to tell us that we are full. To test this hypothesis, I will turn off specific NTS nerve cells to make them unable to receive and pass on meal-related information and measure food intake and body weight. The aim of these studies is to understand whether such a fault in the system is one of the causes underlying the development of obesity and associated metabolic diseases.It is likely that if we learn more about how the gut and brain communicate, we will be able to send these type of messages to the brain with a medication to reduce appetite and improve obesity. To learn the language of gut-brain communication, we first need to decode the words: the chemicals that these cells use to communicate with each other. My research aims to screen the chemical content of a small group of NTS nerve cells that control appetite to help develop new medications.Another aspect of my research is creating a map of the appetite networks in the brain, like a road atlas. I will use techniques that colour specific brain circuits relying meal-related information. I will also turn these circuits on and off on demand and measure food intake. These studies will allow us to understand which part of the network is crucial for appetite regulation.Overall, I aim to decode the function of a group of nerve cells, clarifying the chemicals they make, and the networks they build within our brains to control appetite - an area of knowledge critical to our understanding and treating the obesity epidemic and improving human health.