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Fructose ingestion acutely stimulates circulating FGF21 levels in humans
Open accessAbstract
OBJECTIVE: Fibroblast growth factor 21 (FGF21) is a hormone with pleiotropic metabolic activities which, in rodents, is robustly regulated by fasting and ketogenic diets. In contrast, similar dietary interventions have either no or minimal effects on circulating FGF21 in humans. Moreover, no intervention or dietary challenge has been shown to acutely stimulate circulating FGF21 in either humans or animals. Recent animal data suggest that the transcription factor Carbohydrate Responsive-Element Binding Protein (ChREBP) stimulates hepatic FGF21 expression and that fructose may activate hepatic ChREBP more robustly than glucose. Here, we examined whether fructose ingestion can acutely stimulate FGF21 in humans. METHODS: We measured serum FGF21, glucose, insulin, and triglyceride levels in ten lean, healthy adults and eleven adults with the metabolic syndrome following oral ingestion of 75 g of glucose, fructose, or a combination of the two sugars. RESULTS: FGF21 levels rose rapidly following fructose ingestion, achieved a mean 3.4-fold increase at two hours (P < 0.01), and returned to baseline levels within five hours. In contrast, FGF21 did not increase in the first two hours following ingestion of a glucose load, although more modest increases were observed after three to four hours. Both baseline and fructose-stimulated FGF21 levels were 2-3 fold elevated in subjects with metabolic syndrome. CONCLUSIONS: Fructose ingestion acutely and robustly increases serum FGF21 levels in humans in a pattern consistent with a hormonal response. While FGF21 appears to be critical for the adaptive response to fasting or starvation in rodents, these findings suggest that in humans, FGF21 may play an important role in fructose metabolism.
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In the citing paper
“Starvation30,31, high sugar intake32,33 and dietary protein restriction26 all induce circulating FGF21 levels in humans.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [32]
In the citing paper
“FGF21 is induced by simple-sugar intake in both mice and humans22,32,33, and that sugar-induced production of FGF21 from the liver occurs in a ChREBP-dependent manner22,121.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [32]
In the citing paper
“In addition, in humans, plasma FGF21 levels have been shown to be induced by increases in both glucose and insulin levels (31, 84, 110, 133), supporting a role during refeeding.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [31]
In the citing paper
“The ingestion of a single bolus of fructose or glucose induces plasma FGF21 levels in both lean healthy participants and patients with metabolic syndrome.”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [31]
In the citing paper
“While fructose markedly and acutely increased plasma FGF21 levels in humans, glucose caused a delayed and gradual increase in plasma FGF21 levels (31).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [31]
In the citing paper
“Circulating FGF21 levels are robustly increased by diets that are high in carbohydrate but low in protein”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [138]
In the citing paper
“Both acute carbohydrate ingestion and long-term exposure to high-carbohydrate diets significantly increase liver FGF21 mRNA expression and circulating FGF21 levels”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [138]
In the citing paper
“liver FGF21 production seems to be robustly stimulated by an imbalance in macronutrients, particularly settings of high-carbohydrate but low-protein intake”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [138]
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Metadata
- Authors
- Dushay, J. R., Toschi, E., Mitten, E. K., Fisher, F. M., Herman, M. A., & Maratos-Flier, E.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Broad Institute (US)
- Corresponding author
- Herman, Mark A.
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 4
- Issue
- 1
- Pages
- 51-57
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC4314524
- OpenAlex
- W2048578282
- Cited by
- 233
- References
- 47
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 19 · 2023: 16 · 2022: 22 · 2021: 22 · 2020: 14 · 2019: 28 · 2018: 20 · 2017: 29 · 2016: 22 · 2015: 11
- FWCI
- 8.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- Funders
- JPB Foundation (8UL1TR000170-05)
- Harvard Catalyst/Harvard Clinical and Translational Science Center (1UL1 TR001102-01)
- EMF (R01DK028082)
- MAH (P30DK057521, R01DK100425)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Health Sciences › Medicine › Physiology (medical) › Dietary Effects on Health
- Keywords
- fructose, FGF21, glucose, carbohydrate-responsive element-binding protein, ChREBP, metabolic syndrome, fructose metabolism, insulin, triglycerides, fasting response
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