Beta-defensins in the prevention of obesity

肥胖症在英国和全球范围内已经达到流行病的水平：无论是在成年人还是（从长远来看最令人担忧的）儿童。肥胖和肥胖相关疾病（包括2型糖尿病、心脏病、哮喘和某些形式的癌症）是NHS和福利成本以及生活质量下降的主要原因。在过去的25年里，英国肥胖症的发病率增加了两倍。2014年，苏格兰政府报告称，苏格兰64.6%的成年人（16岁以上）超重，其中27.1%为肥胖。英国议会健康特别委员会于2015年11月发布了一份关于儿童肥胖的报告，要求采取勇敢和大胆的行动来应对这一危机。治疗肥胖及其后果目前估计每年花费NHS 51亿英镑，更广泛的成本估计约为这一数额的三倍。生活方式和社会环境因素显然起着主要作用，但遗传因素也是如此：肥胖已被证明是在家庭中传递的，因此了解哪些基因参与是一个重要的研究优先事项，以便设计适当的治疗方法。可以培育具有特定基因缺失或获得的小鼠，通过这种方式可以制作肥胖或消瘦的模型。这些体重增加或减少的模型可以用来确定哪些途径在肥胖或瘦的小鼠中被加速或减慢，这可以导致设计好的药物来阻止肥胖和促进瘦。我们已经从小鼠中删除了一组基因，发现这些基因的完全丢失会导致动物肥胖。相反，如果我们将这些基因的人类版本植入小鼠体内，那么这些小鼠就会变瘦。总之，这些数据有力地表明，这些特定的基因（β-防御素）在控制体重方面发挥作用，并有可能作为人类肥胖症的药物。我们想让她了解这些老鼠的情况，这样我们就可以为肥胖的人设计好的药物。

Obesity has reached epidemic levels in the UK and globally: both in adults and (most worrying in the longer term) in children. Obesity and obesity-related disease (including type 2 diabetes, heart disease, asthma and some forms of cancer) are major contributors to NHS and welfare costs and to reduced quality of life. The incidence of obesity in the UK has trebled over the last 25 years. In 2014, the Scottish Government reported that 64.6% of adults (aged over 16) in Scotland were overweight, including 27.1% who were obese. The UK Parliament Health Select Committee in Nov 2015 released a report on Childhood Obesity demanding Brave and Bold action to counteract this crisis. Treating obesity and its consequences is currently estimated to cost the NHS £5.1bn every year and the wider costs estimated to be around three times this amount. Lifestyle and social environment factors clearly play major roles, but so too do genetic factors: Obesity has been shown to be passed on in families and so understanding what genes are involved is an important research priority to enable the design of appropriate therapies.Mice can be bred that have loss or gain of particular genes and in this way models of fatness or leanness can be made. These weight increase or reduction models can then be used to identify what pathways are accelerated or slowed down in mice that are fat or thin and this can lead to designing good drugs to stop obesity and promote being lean.We have removed a cluster genes from the mouse and find that complete loss of these genes results in animals that are fat. Conversely, if we put a human version of one of these genes into mice then these mice are lean. Together, these data strongly imply that these particular genes (beta-defensins) have a role in controlling body weight and have potential as drugs for obesity in humans. We seek her to understand what is going on in these mice so we can design good drugs for people who are fat.