ArticleMolecular metabolism2015
Fructose ingestion acutely stimulates circulating FGF21 levels in humans.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02964715 (The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes), which is not on this map. Cited by 142 papers, 3 of them syntheses 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.
The Effect of Empagliflozin on NAFLD in Asian Patients With Type 2 Diabetes
Who cites it
142 citing papers in PubMed, 3 syntheses or guidelines pooled it, 221 citations in OpenAlex.
- Close association between lifestyle and circulating FGF21 levels: A systematic review and meta-analysis.Frontiers in endocrinology · 2022Pooled it
- Pooled it
- KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference.Proceedings of the National Academy of Sciences of the United States of America · 2016Pooled it
- Effects of a two-week modified ketogenic diet on circulating lipoprotein subclasses, GDF15, and FGF21 in obese adults.Journal of translational medicine · 2025Trial
- Fructose-induced FGF21 secretion does not activate brown adipose tissue in Japanese young men: randomized cross-over and randomized controlled trials.Journal of physiological anthropology · 2024Trial
- Meal sugar-protein balance determines postprandial FGF21 response in humans.American journal of physiology. Endocrinology and metabolism · 2023Trial
- Restricting sugar or carbohydrate intake does not impact physical activity level or energy intake over 24 h despite changes in substrate use: a randomised crossover study in healthy men and women.European journal of nutrition · 2023Trial
- Glucose and lipopolysaccharide differentially regulate fibroblast growth factor 21 in healthy male human volunteers - A prospective cross-over trial.Journal of cellular and molecular medicine · 2022Trial
- Trial
- Trial
- FGF21 contributes to metabolic improvements elicited by combination therapy with exenatide and pioglitazone in patients with type 2 diabetes.American journal of physiology. Endocrinology and metabolism · 2022Trial
- Trial
- Antibody-mediated activation of the FGFR1/Klothoβ complex corrects metabolic dysfunction and alters food preference in obese humans.Proceedings of the National Academy of Sciences of the United States of America · 2020Trial
- AKR-001, an Fc-FGF21 Analog, Showed Sustained Pharmacodynamic Effects on Insulin Sensitivity and Lipid Metabolism in Type 2 Diabetes Patients.Cell reports. Medicine · 2020Trial
- The Acute Effects of Simple Sugar Ingestion on Appetite, Gut-Derived Hormone Response, and Metabolic Markers in Men.Nutrients · 2017Trial
- Trial
- Metabolic benefits of ketohexokinase inhibition in individuals with MASLD: a randomized placebo-controlled crossover trial.Nature metabolism · 2026Article
- Perinatal Changes in Serum Fibroblast Growth Factor 21 and Their Association With Postpartum Insulin Resistance in Women With Gestational Diabetes Mellitus.The journal of obstetrics and gynaecology research · 2026Observational
- Acute high-protein feeding induces hepatic amino acid accumulation in diabetic male mice prior to transcriptional adaptation.Physiological reports · 2026Article
- Hepatic FGF21 is not required for fasting metabolism but guides protein appetite post energy depletion.EMBO reports · 2026Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveFibroblast 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.
methodsWe 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.
resultsFGF21 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.
conclusionsFructose 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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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.