FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and mechanistic study without human trial data.
PubMed 35108517 · doi:10.1016/j.cmet.2021.12.024
What was done
Researchers investigated the mechanism and efficacy of fibroblast growth factor 21 (FGF21) in suppressing alcohol intake. An FGF21 analog was administered to alcohol-preferring non-human primates, and the downstream neural circuitry was evaluated to identify specific neuronal subpopulations mediating this effect.
What was found
Administration of an FGF21 analog reduced alcohol intake by 50% in alcohol-preferring non-human primates. Mechanistically, FGF21 suppressed alcohol consumption via a projection-specific subpopulation of KLB-expressing neurons in the basolateral amygdala.
Why it matters
This study defines a specific amygdalo-striatal neural circuit through which FGF21 regulates drinking behavior and demonstrates that FGF21 analogs can lower voluntary alcohol intake in higher primates, highlighting a potential therapeutic mechanism for alcohol use disorder.
Limits
The findings are derived entirely from non-human animal models, and no human clinical data are presented. Specific sample sizes, dosing regimens, duration of effect, and adverse effects were not reported in the abstract.
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.
- supports Human studies show that single nucleotide polymorphisms in genes involved in FGF21 signaling lead to greater alcohol consumption.
- supports Administering an FGF21 analog to alcohol-addicted mice and monkeys decreased their alcohol consumption by 50%.
- supports Mice genetically incapable of producing or releasing FGF21 consume significantly more alcohol than wild-type mice.