LEP and obesity due to melanocortin 4 receptor deficiency: Leptin was one of the first adipose secreted factor discovered to play a role in appetite suppression, where humans and animals deficient in leptin exhibited hyperphagia and early onset obesity, highlighting the important endocrine role that adipose tissue plays in maintaining metabolic homeostasis (Zhang et al., 1994; Halaas et al., 1995; Pelleymounter et al., 1995).