1.Regulation of food intake and energy balance in the mouse. The mouse is an ideal model for the study of energy regulation. Modern technology allows us to follow in close detail minute by minute changes in energy demands, physical activity, body temperature and feeding behaviour of mice. While molecular biology techniques allow us to probe the changes in gene expression of critical areas of the brain that are involved in regulation of food intake. The availability of knock-out and transgenic mouse models allows experimental analysis of the effects of specific genes on feeding behaviour and energy balance. My work will include next generation sequencing technology of specific brain regions and peripheral tissues combined with metabolomics analysis to build an integrated physiological model for the regulation of energy balance in the mouse. I am particularly interested to interact with mathematical biologists to develop such a model. An example of co-ordinated changes in gene expression relating to the fatty acid metabolism in brown adipose tissue revealed by RNA-seq performed by my group is shown in figure 1. Down-regulated genes are shown in green and up-regulated genes shown in red. In this experimental manipulation there is a broad-scale down-regulation in the entire pathway reflecting shutdown of the BAT. Discovering the metabolic factors that cause such co-ordinated changes is a key goal of this research program.
2.Factors influencing susceptibility and resistance to obesity in the Chinese urban population. Obesity is one of the greatest health threats in modern society. It is widely assumed that the major cause of obesity is a gene-environment interaction. Some individuals have a genetic propensity to put on weight which is expressed in the modern environment. Elevated levels of food consumption and decreased levels of energy expenditure are widely cited as the major factors in urban society that promote obesity risk. Yet the evidence for both of these ideas is at best weak. Studies of food intake suggest little change over time, but these studies are marred by the difficulty of accurately measuring food intake. In contrast for energy expenditure we have shown no evidence for a decrease in energy expenditure over the time course of the epidemic (Westerterp and Speakman 2008 International Journal of Obesity) (see figure 2). My work will address the factors that may predispose to obesity in the Chinese urban population including genetic and environmental influences.