Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury.
Level 5 - mechanism / opinion, no new human data
Preclinical animal knockout disease models combined with an acute human challenge biomarker study
PubMed 29107287 · doi:10.1016/j.molmet.2017.08.004
What was done
Researchers investigated circulating fibroblast growth factor 21 (FGF21) responses to acute ethanol intake in humans and mice using a binge drinking paradigm. Ethanol clearance was compared between wild-type (WT) and FGF21-knockout (FGF21-KO) mice. The functional role of FGF21 in chronic alcohol exposure was assessed in WT and FGF21-KO mice across two regimens: a 16-day Lieber-DeCarli ethanol-containing high-fat diet and a 16-week protocol with 30% ethanol in drinking water alongside normal chow.
What was found
In both humans and mice, serum ethanol peaked at 1 hour and was cleared by 6 hours, followed by a robust induction of circulating FGF21 at 6 hours (exact quantitative concentrations and fold changes were not reported in the abstract). Ethanol clearance rates were identical between WT and FGF21-KO mice. In the 16-day Lieber-DeCarli diet model, FGF21-KO mice exhibited higher mortality than WT mice. In the 16-week 30% ethanol drinking water model, no mortality occurred in either group, but FGF21-KO mice developed significant liver pathology compared to WT mice (pathology scores not quantified in the abstract).
Why it matters
This study identifies FGF21 as an acute ethanol-responsive factor in humans and rodents. Rodent knockout models indicate that endogenous FGF21 protects against chronic alcohol-induced hepatic injury and mortality, suggesting a potential pathway for therapeutic exploration in alcoholic liver disease.
Limits
Protective effects on liver pathology and mortality were demonstrated exclusively in mouse knockout models, whereas human evaluation was restricted to acute circulating biomarker kinetics. The abstract reports no sample sizes for human subjects or animal cohorts and provides no numerical values, confidence intervals, or statistical effect sizes for FGF21 induction, mortality rates, or histological liver damage.
Cited by
- supports Alcohol intoxication triggers FGF21 release, which acts as a negative feedback mechanism through a liver-brain signaling axis to decrease subsequent alcohol intake.