Diet is a major factor in the development of obesity, but its interaction with a susceptible genotype is poorly understood. We will assess the prevalence of high fat consumers (HFC) and phenotype groups that appear to be resistant (DIO-R) or susceptible (DIO-S) to diet induced obesity (DIO). DNA banks from HFCs who are lean or obese and from obese children who consume a HF or LF diet will be screened using candidate genes. A rat model of DIO will be investigated to identify diagnostic biomarkers of DIO-R or DIO-S, and to define the mechanisms involved in defence of obesity. We will also study the influence of foetal and early life nutrition on relevant phenotypes. We will develop a web site to provide accessible information on diet, energetics and genetic predisposition to obesity to a lay audience, in particular obese children and their families.
The overall objective of this project is to identify the causes of weight gain on a Westernised, energy dense, high fat diet, and to apply these findings in the diagnosis, prevention and management of obesity in the human population. This will involve examination of the interaction between diet and genetic background in the susceptibility or resistance to obesity, as well as the genetic basis of dietary preference, and the influence of early life nutrition. The risk factors that define predisposition to obesity and the interaction of diet with this susceptibility (diet-induced obesity) will be investigated. The phenotypes associated with food preference and susceptibility to weight gain and obesity on a high fat diet will be described and the genetic basis of this susceptibility investigated through molecular genetic studies. Diagnostic biomarkers of susceptibility or resistance to excess weight gain on a high fat diet and the mechanistic basis of post-dieting weight gain will be investigated a laboratory rodent model of diet-induced obesity. The effect of early life nutrition on dietary preferences in juvenile or adult life, susceptibility to obesity, and the programming of brain energy balance signalling systems will be investigated in parallel clinical and laboratory rodent studies.
The project will advance our understanding of mechanisms that determine why a high fat diet is preferentially selected by some individuals but not by others, and how genetic background interacts with such diets to confer susceptibility or resistance to obesity. A major outcome will be the detailed description of the phenotype that is associated with susceptibility to weight gain on a high fat diet in both the human population and in the rat model, and the association of genetic markers with these phenotypes in humans. There will be further enhancement of our understanding of the role of maternal nutrition and diet composition on the dietary preferences of children/offspring and their susceptibility to develop obesity. Central nervous system correlates of these characteristics will be described. A web-site will be established, targeted specifically at a lay rather than an academic audience. The multi-lingual site will illustrate the basic relationships between diet, energy expenditure and genetic predisposition in the development of obesity, and will be designed to be appealing to all age groups, but particularly children and adolescents, and will feature 'familiar' cartoon-like characters. The web-site is intended to be simultaneously entertaining and educational, and will supplement and reinforce conventional media, containing material that will range from accessible summaries of recent research progress to lifestyle and dietary advice.
Applications: Understanding phenotypic variation in susceptibility to diet-induced obesity in the population will help us better understand how to amplify resistant traits in susceptible individuals. An improved ability to diagnose individuals at risk will allow treatment and preventive measures (dietary and lifestyle advice), including advice during pregnancy, to be more targeted. Such an outcome will benefit individuals, the wider community and healthcare providers. Identifying genes involved in the excess consumption of dietary fat, and in the susceptibility to develop obesity on high fat diets could make an important contribution to our understanding of genetic disposition toward common dietary obesity. Detailed mechanistic studies of rodent models will describe the characteristics conferring susceptibility or resistance to obesity, the interaction of voluntary exercise and obesity, and will delineate the mechanisms underlying the defence of obese body weight. These regulatory processes lie at the root of the problems experienced by obese subjects attempting to lose weight by dieting, and this information may form the basis of lifestyle advice for susceptible individuals, or identify targets for pharmacological manipulation.
Despite the current popular concern surrounding early life nutrition, little is known about how nutritional events influence subsequent physiology. Early nutritional experiences have a major influence on body weight and the probability of developing obesity in later life. It is possible that manipulation of the maternal diet during foetal and early neonatal life may alter the 'settings' of brain control systems regulating energy balance. Our hypothesis is that nutrition during critical phases of development could thus contribute to susceptibility to obesity. Such issues are best addressed in laboratory animal models but experimental outcomes will be applicable to the human situation.
As the pace of scientific advance increases there is an increasing need for information relating to obesity to be made available to the lay public in an accessible format. Complex issues are involved in susceptibility to obesity and there is a critical gap in the range of information available to members of the general public, practitioners and the patients, including children. The obesity web-site will fill the gap that exists between obesity web-sites of academic orientation and the popular press.