A human laboratory study on the link between alcohol administration and circulating fibroblast growth factor 21 (FGF21) in individuals with alcohol use disorder

Growing evidence indicates that the crosstalk between the central nervous system and the periphery plays an important role in the pathophysiology of neuropsychiatric conditions, including addictive disorders. Fibroblast growth factor 21 (FGF21) is part of the liver-brain axis and regulates energy homeostasis, metabolism, and macronutrient intake. In addition, FGF21 signaling modulates alcohol intake and preference, and changes in FGF21 levels are observed following alcohol consumption. To further elucidate the relationship between alcohol use and FGF21, we assessed serum FGF21 concentrations in 16 non-treatment seeking individuals with alcohol use disorder (AUD) in a naturalistic outpatient setting, as well as a controlled laboratory experiment that included alcohol cue-reactivity, alcohol priming, and alcohol self-administration in a bar-like setting. FGF21 levels were stable during the outpatient phase when participants received placebo and had no significant lifestyle changes. During the bar-like laboratory experiment, a robust increase in serum FGF21 concentrations was found after the 2-hr alcohol self-administration session (F3, 49 = 23.39, p < 0.001). Percent change in FGF21 levels positively correlated with the amount of alcohol self-administered but did not reach statistical significance. No significant changes in FGF21 levels were found after exposure to alcohol cues or consuming the priming drink. Given the bidirectional link between FGF21 and alcohol, targeting the FGF21 system may be further examined as a potential pharmacotherapy for AUD.

Automated summary

Growing evidence suggests that the interaction between the central nervous system and the periphery, particularly through fibroblast growth factor 21 (FGF21), plays a crucial role in the development of neuropsychiatric conditions and addictive disorders. This study examined the relationship between alcohol use disorder (AUD) and FGF21 levels in non-treatment seeking individuals using both outpatient and laboratory settings. The findings showed that while FGF21 levels remained stable during the outpatient phase, there was a significant increase in serum FGF21 concentrations following alcohol self-administration in a controlled laboratory experiment. These results highlight the potential of targeting the FGF21 system as a pharmacotherapy for AUD.