Obesity-related mutations of leptin and melanocortin receptors

摘要

In recent years, the molecular approach to human obesity has advanced the understanding of some causes and mechanisms of severe forms of obesity. Single rare mutations largely contribute to the development of some obesity cases. Research was conducted after a meticulous clinical evaluation of individuals with specific biochemical or hormonal anomalies. These obesity cases are very severe and generally start in childhood. This chapter will focus on genetic mutations causing primary defects in the leptin and melanocortin pathways. Although obesity due to mutations of leptin, leptin receptor, proopiomelanocortin, and proconvertase 1 are exceptional, obesity linked to MC4R mutations could represent 2 to 4% of human cases. The phenotypic and endocrine features of these mutations causing a dysfunction in leptin and melanocortin signaling will be reviewed. The contribution of genetic variations of genes encoding the key actors of the leptin and melanocortin pathways in common forms of obesity will also be discussed.