The downregulation of AQP9 during obesity and/or diabetes could represent a compensatory mechanism selected at decreasing substrate availability for de novo TAG synthesis, thereby counteracting the ectopic accumulation of TAG into hepatocytes, and reducing gluconeogenesis, thereby thwarting the progression of hyperglycemia (Gena et al., 2013; Rodríguez et al., 2014, 2015b). Here, AQP9 is linked to obesity due to melanocortin 4 receptor deficiency.