BDNF and obesity due to melanocortin 4 receptor deficiency: The circulating level of BDNF is associated with obesity and diabetes mellitus in humans,21 while systemic administration of BDNF improves glycemic control in db/db mice.22 The liver and pancreatic α-cells might be involved in the underlying mechanism.23,24 In addition, mice with hepatocyte-specific Bdnf deficiency show normal food intake and body weight, but are protected against dietary metabolic abnormalities through enhanced expression of peroxisome proliferator-activated receptor α and fibroblast growth factor 21 (ref. 25).