Proteomic profiling of experimental acute alcohol intoxication reveals FGF21 as a specific ethanol-induced hormone

Background: The effects of acute alcohol intoxication on the human plasma proteome are still largely unexplored. Gaining insights into this relationship could identify factors that are influenced by and influence alcohol consumption. Fibroblast Growth Factor 21 (FGF21), a hormone produced by the liver and associated with alcohol preferences, is currently undergoing Phase 2 clinical trials for metabolic dysfunction and alcohol-related liver disease. We hypothesized that FGF21 is a key endocrine responsive hormone to alcohol in humans. Methods: In a post hoc analysis, we evaluated the effects of five standard units of alcoholic beverages on the plasma proteome in 12 healthy Caucasian men. Participants, fasting for 10 hours, received 0.7 g of alcohol per kg of body weight via gastric infusion, with blood samples collected before and after consumption. Results: The proteomic response to this level of alcohol intoxication was highly specific. Of 1,462 proteins measured, only 11 changed significantly and FGF21 exhibited by far the largest increase (10.5-fold). Conclusion: This study highlights a unique proteomic response to acute alcohol ingestion and supports further exploration of FGF21 mimetics as potential treatments for alcohol-related disorders.