ArticleThe Journal of clinical investigation2014
FGF21 is an endocrine signal of protein restriction.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 364 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
364 citing papers in PubMed, 1 synthesis or guideline pooled it, 579 citations in OpenAlex.
- Close association between lifestyle and circulating FGF21 levels: A systematic review and meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Trial
- Dietary Protein Reduction During Isocaloric Conditions Reduces Body Weight in Men With Overweight or Obesity.Obesity (Silver Spring, Md.) · 2026Trial
- Daily Complementary Feeding With Eggs Improves Fibroblast Growth Factor 21 in Infants.Maternal & child nutrition · 2025Trial
- Rapid benefits in older age from transition to whole food diet regardless of protein source or fat to carbohydrate ratio: Arandomised control trial.Aging cell · 2024Trial
- Meal sugar-protein balance determines postprandial FGF21 response in humans.American journal of physiology. Endocrinology and metabolism · 2023Trial
- Trial
- Trial
- LLF580, an FGF21 Analog, Reduces Triglycerides and Hepatic Fat in Obese Adults With Modest Hypertriglyceridemia.The Journal of clinical endocrinology and metabolism · 2022Trial
- Reduced adaptive thermogenesis during acute protein-imbalanced overfeeding is a metabolic hallmark of the human thrifty phenotype.The American journal of clinical nutrition · 2021Trial
- Validation of the Micronutrient and Environmental Enteric Dysfunction Assessment Tool and evaluation of biomarker risk factors for growth faltering and vaccine failure in young Malian children.PLoS neglected tropical diseases · 2020Trial
- Revisiting gut microbiota-driven ammonia metabolism: from disease burden to physiological adaptation.Gut microbes · 2026Review
- Macronutrient mixtures and interactions in health and disease.Nature reviews. Endocrinology · 2026Review
- Human brown fat metabolism associates with systemic branched-chain amino acids homeostasis.Molecular metabolism · 2026Article
- Protein Decoys, Alcohol, and Energy Intake: Testing a Mechanistic-Ecological Model.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Acute high-protein feeding induces hepatic amino acid accumulation in diabetic male mice prior to transcriptional adaptation.Physiological reports · 2026Article
- Adipose FGF21 signalling mediates the anti-senescence effects of protein restriction.The Journal of physiology · 2026Article
- Differential somatostatin sensitivity of corticotropic and somatotropic responses following amino acid infusion.Endocrine connections · 2026Article
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
304 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Enhanced fibroblast growth factor 21 (FGF21) production and circulation has been linked to the metabolic adaptation to starvation. Here, we demonstrated that hepatic FGF21 expression is induced by dietary protein restriction, but not energy restriction. Circulating FGF21 was increased 10-fold in mice and rats fed a low-protein (LP) diet. In these animals, liver Fgf21 expression was increased within 24 hours of reduced protein intake. In humans, circulating FGF21 levels increased dramatically following 28 days on a LP diet. 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). Finally, while protein restriction altered food intake, energy expenditure, and body weight gain in WT mice, FGF21-deficient animals did not exhibit these changes in response to a LP diet. These and other data demonstrate that reduced protein intake underlies the increase in circulating FGF21 in response to starvation and a ketogenic diet and that FGF21 is required for behavioral and metabolic responses to protein restriction. FGF21 therefore represents an endocrine signal of protein restriction, which acts to coordinate metabolism and growth during periods of reduced protein intake.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.