Beta-defensins in the prevention of obesity

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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.