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

在英国，肥胖是早逝的主要原因，据估计，每周有600人早逝。到目前为止，还没有有效的治疗方法，调节食欲和体重的因素也很大程度上是未知的。胰腺多肽(PP)和多肽YY(PYY)是肠道对食物摄入的反应而释放的激素。最近，它们都被证明在大脑中起到了降低食欲的作用，因此可以被认为是身体在用餐后感到饱的机制的一部分。将这些荷尔蒙注入人体，在减少食物摄入量方面一直显示出强大而持久的效果。开发可以作为减肥药有效使用的类似物的令人兴奋的工作已经在进行中。对于PP和PYY如何在大脑中发挥食欲作用，我们的理解仍然存在很大差距。尽管它们的结构和作用非常相似，但我们知道它们各自对不同的受体有强烈的偏好，因此刺激大脑中不同的食欲信号。通过比较PP和PYY的效果，我将有助于我们从整体上理解控制食物摄入量的途径。

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.