Research
Hormonal
FGF21 is required for the metabolic and behavioral adaptations to protein restriction, including increased energy expenditure, increased food intake, and reduced body weight gain.
This mechanism is specific to rodents; humans do not have FGF21 knockout models. However, it suggests that FGF21 signaling is a critical link between protein intake and metabolic rate. Low protein intake may blunt metabolic adaptation if FGF21 signaling is impaired.
StrongSupportsVERY_HIGH confidence
FGF21-deficient animals did not exhibit these changes in response to a LP diet... FGF21 is required for behavioral and metabolic responses to protein restriction.
Why this rating
Genetic knockout studies (FGF21-KO) provide definitive causal evidence that the hormone is necessary for the phenotype.
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
- 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
- The induction of FGF21 during protein restriction is mediated by the GCN2/eIF2α signaling pathway and requires PPARα.Good
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