NMS and obesity due to melanocortin 4 receptor deficiency: The neural mechanisms that underlie human variability in SPA are distributed processes involving multiple brain regions, neurotransmitters and neuropeptides, including cholecystokinin, corticotrophin releasing hormone, neuromedin, neuropeptide Y (NPY), leptin, and orexin (also known as hypocretin).19 While all are important, in this review we focus on the biological role of central orexin peptides and their receptors with respect to their role in obesity and obesity resistance.