FGF21

FGF21 is a “fasting and stress” hormone, made mainly by the liver, that helps the body switch into energy-conservation and fat-burning mode when food is scarce or metabolism is under strain. Think of it as a metabolic stress signal that retunes how the body uses fuel.

Despite belonging to the fibroblast growth factor family, FGF21 acts as a circulating hormone rather than a typical local growth factor. The liver releases it during fasting, ketogenic states, and certain stresses; it then promotes fat breakdown, ketone production, and glucose uptake, and acts on the brain to influence appetite — notably reducing the preference for sweets and alcohol. It needs a co-receptor called beta-Klotho to act on its target tissues.

FGF21 has attracted intense interest as a drug target for fatty liver disease, obesity, and diabetes, because giving it (or analogs) improves blood lipids and liver fat in trials. An honest caveat: paradoxically, blood FGF21 is often elevated in obesity and type 2 diabetes, suggesting a state of partial FGF21 resistance — so simply having more is not automatically better.