Basal serum levels of FGF21 vary widely among individuals and are generally low in pure strains of laboratory mice (6). Deficiency or overexpression of FGF21 does elicit alterations in metabolic gene expression in the liver and adipose tissue, but without dramatic metabolic phenotypes under normal physiological conditions (7, 8). In contrast, pharmacologic applications of FGF21 in obese and diabetic animals suggest a wide range of effects across multiple tissues with marked anti-obesogenic and anti-diabetic efficacy (1, 2, 4, 9). However, beyond such drastic pharmacological effects in the obese, the possible functions of FGF21 as a circulating hormone in organ-specific physiopathologies have remained elusive.
