Homeostatic sensing of dietary protein restriction: a case for FGF21
Open accessAbstract
Restriction of dietary protein intake increases food intake and energy expenditure, reduces growth, and alters amino acid, lipid, and glucose metabolism. While these responses suggest that animals 'sense' variations in amino acid consumption, the basic physiological mechanism mediating the adaptive response to protein restriction has been largely undescribed. In this review we make the case that the liver-derived metabolic hormone FGF21 is the key signal which communicates and coordinates the homeostatic response to dietary protein restriction. Support for this model centers on the evidence that FGF21 is induced by the restriction of dietary protein or amino acid intake and is required for adaptive changes in metabolism and behavior. FGF21 occupies a unique endocrine niche, being induced when energy intake is adequate but protein and carbohydrate are imbalanced. Collectively, the evidence thus suggests that FGF21 is the first known endocrine signal of dietary protein restriction.
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FGF21 is critical for the detection of protein restriction.
“a separate literature provides strong evidence that FGF21 is critical for the detection of protein restriction”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [61]
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- Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ & Lamming DW, 2018 Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol. 596, 623– 645. 29266268 PMC5813603
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FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism
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Self-citationThe physiological control of eating: signals, neurons, and networks
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Protein Leverage: Theoretical Foundations and Ten Points of Clarification
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Self-citationFGF21 and the physiological regulation of macronutrient preference
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- Authors
- Hill, C. M., Berthoud, H.-R., Münzberg, H., & Morrison, C. D.
- Affiliations
- Pennington Biomedical Research Center (US)
- Corresponding author
- Morrison, Christopher D.
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 51
- Pages
- 125-131
- ISSN
- 0091-3022 (ISSN-L)
- PMC
- PMC6175661
- OpenAlex
- W2805909874
- Cited by
- 68
- References
- 120
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 4 · 2023: 6 · 2022: 9 · 2021: 18 · 2020: 6 · 2019: 14
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Frontiers in Neuroendocrinology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01DK105032, F32DK115137)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- FGF21, protein restriction, amino acid sensing, metabolic homeostasis, energy expenditure, dietary intake, growth, amino acid metabolism, hormone signaling
- MeSH terms
- Animals, Dietary Carbohydrates, Dietary Proteins, Feeding Behavior, Fibroblast Growth Factors, Homeostasis, Diet, Protein-Restricted
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