FGF21 in acute and chronic alcohol consumption

Harmful alcohol use is one of the most common causes for liver cirrhosis. A considerable percentage of cirrhotic patients struggle to stop drinking knowing it might cause their death. Fibroblast growth factor (FGF) 21 and its co-receptor b-Klotho have been implicated in the regulation of alcohol intake in animal experiments and GWAS studies. FGF21 expression was linked to reduced alcohol and sugar preference in mice, and vice versa, fructose and glucagon can induce the expression of FGF21 in humans. It is unclear whether this is also true for alcohol and whether this regulatory mechanism is disrupted in alcohol addiction.

To investigate the effects of alcohol intake on FGF21 expression we enrolled 6 healthy volunteers who ingested a single binge of alcohol (2 g alcohol/kg bodyweight) in fasting state. The binge resulted in an increase of blood alcohol levels to 1.12 (± 0.14) ‰ one hour after intake. FGF 21 increased ten-fold from 399 (± 258)pg/ml at baseline to 3753 (± 1328)pg/ml within two hours after the binge. While blood alcohol levels decreased continuously with a rate of 0.11 (± 0.03) ‰/h, FGF21 levels remained elevated throughout the study period.

Alcohol consumption of 75 patients with cirrhosis of various aetiologies was assessed in interviews/questionnaires, and verified by urinary ethylglucuronid. None of the patients had consumed alcohol immediately before inclusion (verified by urinary ethanol), 13 had elevated ethylglucuronid levels. We found that FGF21 in patients with ongoing alcohol consumption was 2.8-fold higher compared to abstinent patients (p = 0.003).

Our data show that alcohol intake results in a rapid increase in FGF21 levels in humans, possibly as a protective mechanism against intoxication, since FGF21 decreased alcohol intake in mice. The continuous alcohol intake in patients despite high FGF21 levels suggests a dysregulation of FGF21 and/or its receptors.