FGF21 and obesity due to melanocortin 4 receptor deficiency: Moreover, mice and patients exhibit extreme elevations of fibroblast growth factor 21 (FGF21) (15, 27), a key metabolic regulator with pleiotropic effects in liver and adipose tissue (28, 29) that has been associated with resistance to obesity, improved glucose tolerance, and reduced fat accumulation and inflammation in the liver, making it a promising therapeutic target for obesity, nonalcoholic steatohepatitis, and cardiometabolic phenotypes (30–32).