FGF21(Fibroblast growth factor 21) is a protein that in humans is encoded by the FGF21 gene, which is also a member of the fibroblast growth factor (FGF) family. The FGF21 gene is mapped on 19q13.33. Using RT-PCR, Fgf21 was expressed in several types of adipose tissue in mice, including subcutaneous and epididymal fat pads and brown adipose tissue. The level of Fgf21 expression in adipose tissue was comparable to that in liver. FGF21 stimulates glucose uptake in adipocytes but not in other cell types. This effect is additive to the activity of insulin. FGF21 treatment of adipocytes is associated with phosphorylation of FRS2, a protein linking FGF receptors to the Ras/MAP kinase pathway. FGF21 also protects animals from diet-induced obesity when overexpressed in transgenic mice and lowers blood glucose and triglyceride levels when administered to diabetic rodents. Changes in Fgf21 expression due to suckling or nutritional manipulations were associated with changes in circulating free fatty acid and ketone body levels. In differentiated mouse brown adipocytes in culture, Fgf21 treatment increased the expression of thermogenic genes, caused higher total and uncoupled respiration, and enhanced glucose oxidation.