ArticleNature metabolism2025
Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men.
Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
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Who cites it
19 citing papers in PubMed.
- Trial
- Dietary Protein Reduction During Isocaloric Conditions Reduces Body Weight in Men With Overweight or Obesity.Obesity (Silver Spring, Md.) · 2026Trial
- Macronutrient mixtures and interactions in health and disease.Nature reviews. Endocrinology · 2026Review
- Mitokines as bioenergetic stress signals in cardiovascular disease: mitochondrial communication, endocrine adaptation, and translational implications.Journal of bioenergetics and biomembranes · 2026Review
- Adipose FGF21 signalling mediates the anti-senescence effects of protein restriction.The Journal of physiology · 2026Article
- The hallmarks of protein and amino acid restriction in aging and longevity.Cell press blue · 2026Article
- Fibroblast growth factor 21 and its relationship with central precocious puberty in girls.Endocrine connections · 2026Article
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.Nature aging · 2026Article
- Hepatic FGF21 is not required for fasting metabolism but guides protein appetite post energy depletion.EMBO reports · 2026Article
- Female resistance to the metabolic benefits of protein restriction is reversed by ovariectomy in mice.bioRxiv : the preprint server for biology · 2026Article
- A nutrient-hormone axis pivots an energy trade-off between resting thermogenesis and movement expenditure.Journal of sport and health science · 2026Article
- Long-term high-protein diet intake accelerates adipocyte senescence through macrophage CD38-mediated NADMolecular metabolism · 2026Article
- Article
- The impacts of different dietary restriction regimens on aging and longevity: from yeast to humans.Journal of biomedical science · 2025Review
- Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice.bioRxiv : the preprint server for biology · 2025Article
- Manipulating dietary protein and amino acids in the common marmoset Callithrix jacchus impacts circulating metabolites and FGF21 levels.Scientific reports · 2025Article
- Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia.International journal of molecular sciences · 2025Article
- Brain amino acid sensing for organismal amino acid homeostasis.Open biology · 2025Review
- Ketone metabolites in metabolic dysfunction-associated steatotic liver disease progression: optimizing keto-therapeutic strategies.American journal of physiology. Endocrinology and metabolism · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors.
Funding
Abstract
Dietary protein restriction increases energy expenditure and enhances insulin sensitivity in mice. However, the effects of a eucaloric protein-restricted diet in healthy humans remain unexplored. Here, we show in lean, healthy men that a protein-restricted diet meeting the minimum protein requirements for 5 weeks necessitates an increase in energy intake to uphold body weight, regardless of whether proteins are replaced with fats or carbohydrates. Upon reverting to the customary higher protein intake in the following 5 weeks, energy requirements return to baseline levels, thus preventing weight gain. We also show that fasting plasma FGF21 levels increase during protein restriction. Proteomic analysis of human white adipose tissue and in FGF21-knockout mice reveal alterations in key components of the electron transport chain within white adipose tissue mitochondria. Notably, in male mice, these changes appear to be dependent on FGF21. In conclusion, we demonstrate that maintaining body weight during dietary protein restriction in healthy, lean men requires a higher energy intake, partially driven by FGF21-mediated mitochondrial adaptations in adipose tissue.
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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.