INS and obesity due to melanocortin 4 receptor deficiency: The weight gain is further mediated via the following well-described pathways: (i) increased caloric/overeating and altered hypothalamic satiety and appetite regulation (the energy balance model of obesity) and (ii) abnormal fat storage (increased cell size, number, function and growth) due to high insulin secretion/insulin resistance, low-grade inflammation and impaired microbiome (the carbohydrate-insulin model of obesity).