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Alcohol-induced fibroblast growth factor 21 secretion is increased in individuals with alcohol use disorder
Amalie R Lanng1, Lærke S Gasbjerg2, Andrea I F Sucksdorff1
1Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
Background:
Alcohol use disorder (AUD) affects 5% of the global population. Despite its high prevalence, the pathophysiology of AUD remains enigmatic, hindering the development of novel therapeutics. Interestingly, the liver hormone fibroblast growth factor 21 (FGF21), which is currently in late-stage clinical trials for the treatment of non-alcoholic steatohepatitis, has been implicated by recent genome-wide association studies as a regulator of alcohol consumption.
Methods:
This study aimed to evaluate plasma responses of FGF21 to an alcohol challenge in three groups: 15 males with AUD, 15 healthy males with a father with AUD (Predisposed), and 15 healthy males without any predisposition to AUD (Controls). All participants were investigated after an overnight fast. Assessments, including blood sampling and visual analog scale-assessed desire for alcohol intake, were performed before and for 10 h after ingesting 0.5 g alcohol per kg body weight over 10 min.
Results:
The three groups were age and body-mass index-matched and had normal plasma concentrations of transaminases and FibroScan®-assessed elastography. Baseline FGF21 concentrations did not differ between groups, but individuals with AUD exhibited greater FGF21 responses to alcohol (area under the curve (AUC0-600 min): 954 ± 665 ng/ml × min (mean (standard deviation)) compared to Controls (AUC0-600 min: 453 ± 333 ng/ml × min, P = 0.03) but not Predisposed (AUC0-600 min: 556 ± 429 ng/ml × min, P = 0.11).
Conclusion:
In conclusion, we demonstrate greater alcohol-induced FGF21 responses in individuals with AUD compared to healthy individuals without paternal predisposition to AUD, suggesting a role for FGF21 in AUD pathophysiology.
Insights
Individuals with alcohol use disorder (AUD) show significantly higher fibroblast growth factor 21 (FGF21) plasma responses after alcohol consumption compared to healthy controls. This suggests FGF21 plays a role in AUD pathophysiology.
Area of Science:
- Endocrinology
- Neuroscience
- Genetics
Background:
- Alcohol use disorder (AUD) impacts 5% of the global population, yet its underlying mechanisms remain unclear, impeding new therapeutic development.
- Fibroblast growth factor 21 (FGF21), a liver hormone in clinical trials for non-alcoholic steatohepatitis, is emerging as a potential regulator of alcohol consumption.
- Genome-wide association studies have implicated FGF21 in alcohol consumption patterns.
Purpose of the Study:
- To investigate plasma FGF21 responses to a controlled alcohol challenge in individuals with AUD.
- To compare FGF21 responses between individuals with AUD, healthy individuals with a family history of AUD (Predisposed), and healthy individuals without AUD predisposition (Controls).
Main Methods:
- Three groups of 15 males each (AUD, Predisposed, Controls) underwent an alcohol challenge (0.5 g/kg body weight).
- Plasma FGF21 levels and desire for alcohol were assessed before and for 10 hours after alcohol ingestion.
- Participants were age and BMI-matched with normal liver function tests and liver stiffness.
Main Results:
- Baseline FGF21 levels did not differ significantly among the three groups.
- Individuals with AUD demonstrated a significantly greater area under the curve (AUC) for plasma FGF21 response to alcohol compared to Controls (P=0.03).
- The FGF21 response in the AUD group was not significantly different from the Predisposed group (P=0.11).
Conclusions:
- Alcohol consumption elicits a heightened FGF21 response in individuals with AUD compared to healthy controls.
- These findings suggest a potential role for FGF21 in the pathophysiology of alcohol use disorder.
- FGF21 may represent a novel biomarker or therapeutic target for AUD.
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