ReviewFrontiers in endocrinology2021
Nutritional Regulation of Hepatic FGF21 by Dietary Restriction of Methionine.
Review in Frontiers in endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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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
13 citing papers in PubMed, 21 citations in OpenAlex.
- Dietary sulfur amino acid restriction in humans with overweight and obesity: a translational randomized controlled trial.Journal of translational medicine · 2024Trial
- Methionine-supplemented longevity diet increases growth hormone, GLP-1, and FGF21; reduces frailty; and promotes healthspan.Cell metabolism · 2026Article
- Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice.GeroScience · 2026Article
- Mutation in IR or IGF1R produces features of long-lived mice while maintaining metabolic health.JCI insight · 2025Article
- Dietary methionine restriction started late in life promotes healthy aging in a sex-specific manner.Science advances · 2025Article
- Article
- History and future of leptin: Discovery, regulation and signaling.Metabolism: clinical and experimental · 2024Review
- Mitochondrial complex I inhibition triggers NADGeroScience · 2024Article
- Long term methionine restriction: Influence on gut microbiome and metabolic characteristics.Aging cell · 2024Article
- Cysteine-lowering treatment with mesna against obesity: Proof of concept and results from a human phase I, dose-finding study.Diabetes, obesity & metabolism · 2023Article
- Lysine Deprivation Suppresses Adipogenesis in 3T3-L1 Cells: A Transcriptome Analysis.International journal of molecular sciences · 2023Article
- The gut signals to AGRP-expressing cells of the pituitary to control glucose homeostasis.The Journal of clinical investigation · 2023Article
- Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
FGF21 is a potent metabolic regulator of energy balance, body composition, lipid metabolism, and glucose homeostasis. Initial studies reported that it was increased by fasting and the associated increase in ketones, but more recent work points to the importance of dietary protein and sensing of essential amino acids in FGF21 regulation. For example, dietary restriction of methionine produces a rapid transcriptional activation of hepatic FGF21 that results in a persistent 5- to 10-fold increase in serum FGF21. Although FGF21 is a component of a complex transcriptional program activated by methionine restriction (MR), loss-of-function studies show that FGF21 is an essential mediator of the resulting effects of the MR diet on energy balance, remodeling of adipose tissue, and enhancement of insulin sensitivity. These studies also show that FGF21 signaling in the brain is required for the MR diet-induced increase in energy expenditure (EE) and reduction of adiposity. Collectively, the evidence supports the view that the liver functions as a sentinel to detect and respond to changes in dietary amino acid composition, and that the resulting mobilization of hepatic FGF21 is a key element of the homeostatic response. These findings raise the interesting possibility that therapeutic diets could be developed that produce sustained, biologically effective increases in FGF21 by nutritionally modulating its transcription and release.
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Registered trials
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