Genetic strategies to understand physiological pathways regulating body weight

Body weight is a highly heritable trait across species. In humans, genetic variation plays a major role in determining the inter-individual differences in susceptibility or resistance to environmental factors which influence energy intake and expenditure. In this review, I discuss how genetic studies have contributed to our understanding of the central pathways that govern energy homeostasis. The study of individuals harboring highly penetrant genetic variants that disrupt the leptin–melanocortin pathway has informed our understanding of the physiological pathways involved in mammalian energy homeostasis.