Fibroblast growth factor 21

FGF21
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5VAQ, 6M6F, 6M6E
Identifiers
Aliases	FGF21, fibroblast growth factor 21
External IDs	OMIM: 609436; MGI: 1861377; HomoloGene: 10428; GeneCards: FGF21; OMA:FGF21 - orthologs
Gene location (Human)
Chr.	Chromosome 19 (human)
End	48,758,333 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	45,264,914 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; pancreatic ductal cell; ; muscle of thigh; ; female breast; ; mammary gland; ; lactiferous gland; ; gastrocnemius muscle; ; head; ; mouth; ; blood;
	Top expressed in
	pyloric antrum; ; embryo; ; thymus; ; calvaria; ; liver; ; islet of Langerhans; ; left lobe of liver; ; axial skeleton; ; cornea; ; spermatid;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	growth factor activity; protein binding; fibroblast growth factor receptor binding;
Cellular component	extracellular region; extracellular space;
Biological process	endothelial cell apoptotic process; positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway; positive regulation of ERK1 and ERK2 cascade; positive regulation of cell population proliferation; positive regulation of glucose import; cell-cell signaling; cellular response to glucose stimulus; fibroblast growth factor receptor signaling pathway; regulation of low-density lipoprotein particle clearance; response to nutrient levels; negative regulation of endothelial cell apoptotic process; response to activity; signal transduction; cellular response to low-density lipoprotein particle stimulus; endoplasmic reticulum unfolded protein response; negative regulation of neuron death; positive regulation of triglyceride catabolic process; response to methionine; cellular response to glucagon stimulus; regulation of signaling receptor activity; positive regulation of cold-induced thermogenesis;
	Sources:Amigo / QuickGO
Orthologs
	26291
	56636
	ENSG00000105550
	ENSMUSG00000030827
	Q9NSA1
	Q9JJN1
	NM_019113
	NM_020013
	NP_061986
	NP_064397
	Wikidata
View/Edit Human	View/Edit Mouse

Fibroblast growth factor 21 (FGF-21) is a protein found in humans and other mammals that is encoded by the FGF21 gene. This protein is a member of the fibroblast growth factor (FGF) family and its endocrine subfamily along with FGF23 and FGF15/19. FGF21 is the primary endogenous agonist of the FGF21 receptor, which is composed of the FGF receptor and co-receptor β-Klotho.

Members of the FGF family are broad-spectrum mitogens important to survival activities. FGFs are involved in biological processes throughout the body including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. FGFs act through a family of four FGF receptors. Binding is complicated and requires both interaction of the FGF molecule with an FGF receptor and binding to heparin through a heparin binding domain. Endocrine FGFs lack a heparin binding domain and thus can be released into the circulation.

FGF21 is a hepatokine, a hormone secreted primarily by the liver as shown by the Potthoff lab. Among other activities, FGF21 regulates simple sugar intake and preferences for sweet foods via signaling through FGF21 receptors in the hypothalamus and correlates with reduced dopamine neurotransmission within the nucleus accumbens. The Potthoff lab followed up on their discovery and later revealed that FGF21 signaling to the ventromedial hypothalamus suppresses sugar intake by enhancing the activity of glucose-excited and glucose-inhibited neurons in response to high, but not low, glucose levels. The Potthoff lab was also the first to demonstrate that FGF21 has direct actions on adipose tissues, where it can increase acute insulin sensitivity and glucose uptake. Initially thought of as a starvation hormone, FGF21 is now described as "an endocrine mediator of the intracellular stress response to various nutritional manipulations, including excess sugars and alcohol, caloric deficits, a ketogenic diet, and amino acid restriction".

A single-nucleotide polymorphism of the FGF21 gene – the FGF21 rs838133 variant (frequency 44.7%) – has been identified as a genetic mechanism responsible for the sweet tooth behavioral phenotype, a trait associated with cravings for sweets and high sugar consumption, in both humans and mice.