Research
Hormonal
The induction of FGF21 during protein restriction is mediated by the GCN2/eIF2α signaling pathway and requires PPARα.
This is a basic science mechanism. It explains that the body detects low amino acids via the GCN2 kinase, which then triggers FGF21 production. This pathway is conserved in humans, suggesting that amino acid sensing is key to metabolic regulation.
GoodSupportsHIGH confidence
LP-induced increases in FGF21 were associated with increased phosphorylation of eukaryotic initiation factor 2α (eIF2α) in the liver, and both baseline and LP-induced serum FGF21 levels were reduced in mice lacking the eIF2α kinase general control nonderepressible 2 (GCN2).
Why this rating
Strong genetic evidence using knockout mice (Gcn2-KO, Ppara-KO) showing blunted FGF21 response.
Source
FGF21 is an endocrine signal of protein restriction
Thomas Laeger et al. · Journal of Clinical Investigation · 2014
DOI 10.1172/jci74915
mechanism_only · n=17Cited 590×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
More from this paper
- FGF21 is required for the metabolic and behavioral adaptations to protein restriction, including increased energy expenditure, increased food intake, and reduced body weight gain.Strong
- Dietary protein restriction, independent of energy intake, robustly increases circulating FGF21 levels in both rodents and humans, whereas energy restriction alone decreases or does not increase FGF21.Good
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