Alcohol-induced fibroblast growth factor 21 secretion is increased in individuals with alcohol use disorder

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 (R)-assessed elastography. Baseline FGF21 concentrations did not differ between groups, but individuals with AUD exhibited greater FGF21 responses to alcohol (area under the curve (AUC(0_600 min)):954 +/- 665 ng/ml x min (mean (standard deviation)) compared to Controls (AUC(0_600 min): 453 +/- 333 ng/ml x min, P = 0.03) but not Predisposed (AUC(0_60 0 min): 556 +/- 429 ng/ml x 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.