Genetic, molecular and physiological mechanisms involved in human obesity: Society for Endocrinology Medal Lecture 2012

The health consequences of obesity represent one of the major public health challenges of our time. Whilst the role of environmental drivers such as reduced physical activity and increased food intake is widely acknowledged, the importance of biological factors which influence individual variation in weight is less readily recognised. Considerable evidence suggests that genetic factors influence a person's weight in a given environment and that these genetic influences are more potent at the extremes of the body mass index (BMI) distribution. The discovery that genetic disruption of certain pathways can lead to severe obesity has informed our current understanding of how body weight is regulated by brain circuits that regulate appetite and energy expenditure. These studies provide a framework for investigating patients and ultimately may guide the development of more rational-targeted therapies for genetically susceptible individuals with severe obesity.