POMC and obesity due to melanocortin 4 receptor deficiency: Lipotoxicity has been linked to ER stress and the downstream melanocortin system, in that the suppression of mitofusin2 (Mfn2) in proopiomelanocortin (POMC) neurons causes stress in the ER, thus altering the processing of melanocyte-stimulating hormone (α-MSH) and causing leptin resistance and obesity.