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. The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.