A study published in the journal Proceedings of the National Academy of Sciences reveals a previously unrecognised liver-brain pathway which regulates alcohol consumption in humans, and which could in the future be targeted therapeutically to suppress consumption in problem drinkers.
David J Mangelsdorf from the University of Texas Southwestern Medical Center and colleagues performed the largest genome-wide association meta analysis and replication study to date analysing alcohol intake in more than 105,000 individuals of European descent and identified a genetic basis for alcohol consumption during non addictive drinking.
The researchers found that a locus in the gene encoding β-Klotho is associated with alcohol consumption. β-Klotho is an essential receptor component for the endocrine FGFs, FGF19 and FGF21. Using mouse models and pharmacologic administration of FGF21, the researchers identified that β-Klotho in the brain controls alcohol drinking. Mice lacking β-Klotho in the brain showed significantly increased alcohol preference and consumption, compared with mice with β-Klotho. Administration of FGF21 failed to inhibit alcohol preference in mice lacking β-Klotho, suggesting that the effects of FGF21 on alcohol consumption depend on β-Klotho expression in the brain. It was also found that mice lacking β-Klotho did not show any difference in measures of anxiety, compared with mice with b-Klotho.
According to the authors, the results suggest that a pathway operating between the liver and brain and involving FGF21 and β-Klotho plays a role in regulating alcohol drinking in humans. It’s hoped this could serve as a potential “pharmacologic target” for reducing alcohol consumption.
Source: KLB is associated with alcohol drinking, and its gene product β-Klotho is necessary for FGF21 regulation of alcohol preference. David J. Mangelsdorf et al. Proceedings of the National Academy of Sciences.