INS and obesity due to melanocortin 4 receptor deficiency: Expanding on the previous knowledge that brain ER stress underlies neurodegenerative diseases [78] a number of studies have causally linked brain ER stress to the development of metabolic syndrome and related disorders such as overeating, obesity, leptin resistance, insulin resistance, beta-cell dysfunction and hypertension [79,80,81,82] under conditions of overnutrition [79,83] and related inflammatory insults [82].