Since 1994, the number of proposed obesity susceptibility genes has grown steadily. The latest update of the Human Obesity Gene Map reported 127 candidate genes for obesity-related traits [29]. Results of large-scale studies suggest that obesity is strongly associated with genetic variants in the melanocortin-4 receptor (MC4R) gene, adrenergic β3 receptor (ADRB3) gene, prohormone convertase 1 (PCSK1) gene, brain-derived neurotrophic factor (BDNF) gene, and endocannabinoid receptor 1 (CNR1) gene (Table 1). Relevance of those putative genes confer to the development of obesity has been recently summarized [9, 22]. Hypothalamic leptin-melanocortin system is critical for energy balance in humans, because disruption of this network causes the most severe obesity phenotypes [30–32].
