Given the endocannabinoid system's key role in energy and metabolic homeostasis, abnormalities in this system play a central role in the initiation and progression of obesity and MetSyn, possibly by altering appetite and energy balance, increasing lipid production and fat accumulation, impairing glucose and insulin production (which leads to insulin resistance), and altering gut microbiome activity[24–25]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.