Abstract At one level, obesity is clearly a problem of simple physics,aresultofeatingtoomuchandnotexpendingenough energy.Themorecomplexquestion,however,iswhydosome people eat more than others? Studies of human and mouse genetics over the past two decades have uncovered a number ofpathwayswithinthebrainthatplayakeyroleinthecontrol of food intake. A prime example is the leptin–melanocortin pathway, which we now knowgreatlycontributestomammalian appetitive behaviour. However, genetic disruption of this pathwayremainsrareanddoesnotrepresentthemajorburden of the disease that is carried by those of us with ‘common obesity’. In recent years, genome-wide association studies have revealed more than 100 different candidate genes linked to BMI, with most (including many components of the melanocortin pathway) acting in the central nervous system and influencing food intake. So while severe disruption of the melanocortin pathway results in severe obesity, subtle variationsinthesegenesinfluencewhereyoumightsitinthenormal distribution of BMI. As we now enter this ‘post-genomics’ world, can this new information influence our treatment and management of obese patients?
Keywords Appetite .Bodyweight .Foodintake .Genetics . Hypothalamus .Melanocortin .Obesity .Review