Complex interrelated neuronal circuits have developed in the mammalian brain to regulate many aspects of feeding behaviour. An increased understanding of how peripheral energy signals act upon these circuits to regulate food intake is essential for effective treatment of the current obesity crisis. We employ an holistic approach from molecular mechanisms to whole animal physiology and assessment of behaviour. Our approaches include in vitro cell line studies, quantitative gene expression analysis, neuroanatomical mapping studies, generation of tissue specific knock out mice and studies in healthy volunteers and obese patients.

We have shown that the gut hormone peptide YY (PYY) regulates feeding behaviour in rodents and humans and identified that the neuropeptide Y2 receptor is crucial for the anorectic effects of PYY. By generating mice-lacking PYY we have shown that this hormone plays a crucial role in the regulation of body weight. Moreover, we have shown that infusion of PYY reduces food intake in obese human subjects. More recently using fMRI in healthy male volunteers we have shown that PYY modulates neuronal activity within both homeostatic (hypothalamic and brainstem) and hedonic (orbitofrontal cortex) brain regions. We are currently investigating how whole brain circuits involved in homeostasis and reward respond to different stimuli depending on the nutritional status of the animal (fasted/fed/normal weight, obese).

Bariatric surgery is the most effective weight-loss treatment for morbidly obese patients ameliorating obesity co-morbidities and decreasing mortality. However, despite its widespread use, the mechanisms underlying the benefits of bariatric (weight loss) surgery are largely unknown. One of the research focuses of the group is to investigate how bariatric surgery results in marked appetite reduction and weight loss by studying the effects of this surgery (in rodents and humans) on peripheral energy signals and the neural circuits whichregulate feeding behaviour.