Fasting metabolic hormone
Fibroblast growth factor 21 (FGF21)
Also searched as Fibroblast growth factor 21 (FGF21).
You want it responsive: FGF21 is the body's fasting-adaptation hormone, improving insulin sensitivity and lipid handling.
In depth
The liver-secreted hormone induced during fasting — the endocrine signal that mobilizes fat, drives ketogenesis, and sharpens insulin sensitivity.
What drives it
Fatty-acid oxidation increases it.
Inagaki 2007, Cell Metab 5:415 — FGF21 is induced directly by PPARα in the liver during fasting, the endocrine mediator of the adaptive starvation response. Knockout-anchored in both directions. The founding paper is titled 'endocrine regulation of the fasting response by PPAR-alpha-mediated induction of fibroblast growth factor 21' (Inagaki 2007), and PPAR-alpha is required for FGF21 induction in response to fasting and in the early post-prandial phase. PPAR-alpha-null mice show the mirror phenotype — impaired ketogenesis and hepatic steatosis on fasting — and giving FGF21 to those mice raised beta-hydroxybutyrate about threefold, restoring roughly 30 percent of wild-type levels, and significantly reduced hepatic triglyceride accumulation. FGF21 partially rescues the PPAR-alpha-null fasting phenotype. But induced is not required: a paper is titled 'fibroblast growth factor 21-null mice do not exhibit an impaired response to fasting' — despite strong fasting induction of FGF21 in wild-types, FGF21-null mice showed only limited impairments (mild blunting of gluconeogenic transcription, hepatic triglyceride accumulation, reduced fatty-acid-oxidation gene expression). The hormone is a modulator of the fasting response, not its linchpin.
What it drives
It increases Insulin sensitivity.
Kharitonenkov 2005, J Clin Invest 115:1627 — FGF21 improves glucose and insulin; transgenic FGF21 yields a lean, insulin-sensitive phenotype. PMID 15902306. Gain-of-function in vivo: liver-directed FGF21 transgenic mice (ApoE promoter, ~50-fold higher hepatic FGF21 than fasted wild-type) showed significant reductions in serum cholesterol, glucose and insulin — lower insulin at lower glucose is the signature of improved sensitivity rather than suppressed secretion. Independently replicated by a second group generating FGF21 transgenics with the same promoter. Mechanism is partly central, not purely hepatic: beta-Klotho is expressed in discrete hypothalamic areas whose deletion abrogates FGF21's metabolic effects, and central FGF21 requires intact sympathetic tone to act at the periphery. PMID 15902306
Blends that modulate it
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