ALCOHOL SUPERVISOR

 ALCOHOL; NOT TO ADDICTION 

Alcohol is a widely consumed drug in western societies that can lead to addiction. A small shift in consumption can have dramatic consequences on public health. 

It is 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, it is shown that β-Klotho in the brain controls alcohol drinking. These findings reveal a mechanism regulating alcohol consumption in humans that may be pharmacologically tractable for reducing alcohol intake.

Excessive alcohol consumption is a major public health problem worldwide. Although drinking habits are known to be inherited, few genes have been identified that are robustly linked to alcohol drinking. Meta-analysis and replication study among >105,000 individuals of European ancestry and identified β-Klotho (KLB) as a locus associated with alcohol consumption (rs11940694; P = 9.2 × 10⁻¹²). Β-Klotho is an obligate co receptor for the hormone FGF21, which is secreted from the liver and implicated in macronutrient preference in humans. Brain-specific β-Klotho KO mice have an increased alcohol preference and that FGF21 inhibits alcohol drinking by acting on the brain. These data suggest that a liver–brain endocrine axis may play an important role in the regulation of alcohol drinking behavior and provide a unique pharmacologic target for reducing alcohol consumption.

The UTSW team worked with other research teams across the U.S., Europe and in China to see if there is a gene for controlled drinking. They did what’s called a genome-wide association study, screening all the genes in people to see if they could associate it with behavior.

They think they found such a link with beta-Klotho. Like so many genes, it doesn’t act by itself but works with genes called FGF21 and FGF19. These two genes control hormones with the same names that are associated with alcohol preferences, as well as for craving sweet foods.

Tests in mice showed that when they did not have beta-Klotho, they strongly preferred water laced with alcohol to plain water, even when dosed with FGF21 hormone. Monkeys given FGF21 hormone crave sweet drinks less.