Although numerous studies have focused on how the central ECS orchestrates peripheral metabolic responses, both peripheral CB receptor and endocannabinoid levels mediate local responses whose functional dysregulation is associated with obesity, such as BAT thermogenesis, lipid metabolism, leptin and insulin resistance, immune response, gastrointestinal tract functions, and microbiota [14]. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.