Molecular basis of obesity disorders

This chapter introduces obesity, the accumulation of body fat caused by an imbalance of energy intake and energy output, and genetic obesity disorders. In a small percentage of people with obesity, a genetic defect can be identified as the main cause of their obesity. These disorders are often divided into genetic syndromes with and without intellectual disability or developmental delay, syndromic obesity, and nonsyndromic monogenic obesity. Prader-Willi syndrome is the most common form of syndromic obesity, whereas mutations in the melanocortin-4-receptor (MC4R) gene are most frequently causing nonsyndromic monogenic obesity. Both syndromes are characterized by severe hyperphagia, (increased appetite and low satiety). Many more genetic obesity disorders have been discovered in the past 30 years, of which some will be discussed in this chapter. Finally, therapy and current developments in personalized treatment aimed at restoring the leptin-melanocortin pathway will be discussed.