Fibroblast growth factor 21 is a liver-secreted peptide hormone that in humans is encoded by the FGF21 gene.
Together with FGF19 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.
FGFs are 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 addition to its action as a hormone, FGF21 may be able to act in an autocrine fashion in fat cells, or possibly also in a paracrine manner in the pancreas.
Gene location is at Chromosome 19.
It directly regulating energy metabolism in various tissues, and 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.
It is a single-chain protein containing 209 amino acid residues.
FGF21 is involved in the regulation of lipid, glucose, and energy metabolism.
It can be synthesized in several organs and tissues.
FGF21 mainly enters into the circulation by the liver, in amounts typically responding to stress or dietary factors such as caloric or protein intake.
FGF21 can operate in an autocrine, paracrine or endocrine mode.
FGF21 expression and organ responses to the hormone appear to occur under different nutritional or physiological situations: FGF21 is selectively increased in the liver by fasting, by overfeeding in the pancreas, by exercise in muscle, and by cold exposure in brown adipose tissue.
FGF21 promotes glucose uptake in fat.
FGF21 in the liver stimulates gluconeogenesis.
Under dietary protein restriction, FGF21 plays a homeostatic role leading to extend lifespan and improves metabolic health.
Facilitates metabolic function, regulates energy homeostasis and has potential beneficial effects on obesity and diabetes.
Long-term low-protein diets increase FGF21 activation in the brain, leading individuals to behaviorally compensate by preferring foods lower in fat and carbohydrates and higher in protein.
Conditions that require the mobilization of energy stores induce hepatic and brown adipose tissue derived FGF21, while conditions that promote energy storage induce white adipose tissue and pancreatic FGF21.
FGF21 is expressed in numerous tissues, including liver, brown adipose tissue, white adipose tissue and pancreas where it favors digestive enzyme secretion.
Skeletal muscle produces FGF21.
FGF21 release from the liver is enhanced during exercise, apparently accompanying increased lipolysis and ketogenesis in fat tissue,
increased hepatic glycogen degradation and enhanced glucose output from the liver.
There is a correlation between circulating levels of FGF21 and body mass index (BMI).
The ingestion of fructose has been found to rapidly and sharply increase serum FGF21 levels for up to 4 hours, returning to normal by hour 5.
FGF21 is one of the most potent insulin sensitizers.
FGF21 stimulates glucose uptake in adipocytes but not in other cell types.
This effect is additive to the activity of insulin.
FGF21 induces the insulin-sensitizing hormone adiponectin.
Serum FGF21 levels are significantly increased in obesity and in patients with type 2 diabetes mellitus (T2DM): suggesting a state of FGF21-resistance.
Elevated levels also correlate with liver fat content in non-alcoholic fatty liver disease.
FGF21 level positively correlate with BMI in humans, again suggesting obesity as a FGF21-resistant state.
Both high sugar and low protein diets can elevate FGF21.
Circulating FGF21 levels may have prognostic value for the early detection of injury in patients with liver transplantation.
FGF21 can inhibit mTORC1 in the liver and stimulate adiponectin secretion from fatty tissues, thereby inhibiting aging-associated metabolic syndrome.
FGF21 protects against diabetic cardiomyopathy.
The anti-inflammatory effects of FGF21 may primarily be due to inhibition of NF-κB in macrophages.
A single-nucleotide polymorphism (SNP) of the FGF21 gene 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.
Obese individuals systemically given FGF21 can increase energy expenditure, trigger body weight reduction, and reduce abnormally high circulating insulin, triglycerides, and LDL-cholesterol levels.
FGF21 and its analogs may prove particularly effective in the treatment of metabolic syndrome.
FGF21 administration causes the reduction of sugar and alcohol intake, and to have anti-toxic or anti-inflammatory effects in the liver and pancreas.
FGF21 is capable of crossing the blood-brain barrier, and in fact, some of the effects of FGF21 administration on metabolic variables and on food preferences may be mediated through its action in brain pathways.
Fructose induces FGF2 causing a rise in FGF21 levels in serum.
A marked increase in circulating FGF21 in humans is induced by the consumption of alcohol, and alcohol consumption inhibits further drinking.