Pathways of action of the potent anorexigenic gut hormones pancreatic polypeptide and peptide YY.

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Obesity is the major cause of early death in the UK, accounting for an estimated 600 prematuredeaths per week. As yet there are no effective treatments and the factors which regulate appetiteand body weight are largely unknown.Pancreatic polypeptide (PP) and Peptide YY (PYY) are hormones released from the gut inresponse to food intake. Recently they have both been shown to act in the brain to reduceappetite, and can therefore be thought of as part of the body‘s mechanism of feeling full after ameal. Infusions of these hormones into humans have consistently shown powerful and sustainedeffects in lowering food intake. Exciting work is already underway to develop analogues that canbe effectively administered as weight-loss drugs.There remains a large gap in our understanding of how PP and PYY exert their appetite-reducingeffects in the brain. Although their structure and effects are very similar, we know that they eachhave a strong preference for different receptors and therefore stimulate different appetite signals inthe brain. By comparing and contrasting the effects of PP and PYY, I will contribute to our overallunderstanding of the pathways that control of food intake.