ER stress in obese patients relates to leptin and insulin resistance not only in peripheral tissues but also in central tissue, as leptin and insulin are important anorexigenic hormones acting on the hypothalamus, which exhibited elevated expression of ER stress markers such as PERK and IRE1 in the course of obesity and associated pathologies [29,30]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.