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Concept
FGF21
Summary
Fibroblast growth factor 21 is a liver-secreted peptide hormone that in humans is encoded by the FGF21 gene. Together with FGF19 (FGF15 in rodents) and FGF23, this protein is a member of the endocrine subgroup within the fibroblast growth factor (FGF) family. FGF21 is a potent, extracellularly acting metabolic regulator, whose action was discovered through in vitro phenotypic screening and diet manipulation studies in rodents., unlike canonical growth-stimulating FGFs known to stimulate mitosis, differentiation and angiogenesis in their target tissues, FGF21 exerts its action by activating FGF21 receptors located in the cell membrane of target cells. Each FGF21 receptor is composed of a transmembrane FGF receptor protein (either FGFR1, FGFR2 or FGFR3), and its complexing co-receptor β-Klotho. Loss of β-Klotho abolishes all effects of FGF21 in vitro and in vivo. In addition to its action as a hormone, FGF21 may be able to act in an autocrine fashion (typically in fat cells), or possibly also in a paracrine manner in the pancreas.
Apart from directly regulating energy metabolism in various tissues, FGF21 also regulates simple sugar intake and preferences for sweet foods via signaling through FGF21 receptors in the paraventricular nucleus of the hypothalamus and correlates with reduced dopamine neurotransmission within the nucleus accumbens. Attempts are under way to develop metabolic medicines using various FGF21 analogs, mimetics or sensitizers of the FGF21 pathway.
It is a single-chain protein containing 209 amino acid residues, which is encoded by the mammalian FGF21 gene.
FGF21 is beneficially involved in the regulation of lipid, glucose, and energy metabolism. It can be synthesized in several organs and tissues, but it is mainly or solely exported into the circulation by the liver, in amounts typically responding to stress or dietary factors such as caloric or protein intake. Depending on the relation between production and target sites, FGF21 can operate in an autocrine, paracrine or endocrine mode.
Official source
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