At variance with the idea of a possible relationship between LCN-2 upregulation and the anorexigenic effects induced by the overactivity of the melanocortin 4 receptor- (MC4R-) pathway [97, 98], pioglitazone treatment failed to stimulate an increase of body weight in ALS patients and in SOD1 mice [102], a lack of effect described by the hypothesis of defective melanocortin system and downregulation of proopiomelanocortin (POMC) neurons in ALS. The gene discussed is MC4R; the disease is amyotrophic lateral sclerosis.