A liver hormone called FGF21 could be the solution to control a major public health problem: alcohol consumption. The hormone acts directly on a brain receptor sending a message to stop drinking but it only works with people that have the β-Klotho gene.

Alcohol drinking has been related to genetics, and it is known to be partly inherited. There are not many studies that confirm which genes make people drink too much alcohol. The study made by researchers from Imperial College London, King’s College London and UT Southwestern Medical Center, found for the first time a liver-brain connection that can regulate alcohol consumption.

Genetic influences are hard to prove because the effect of individual genes is insignificant. A study must involve thousands to show there is a genetic relation regarding a particular condition and the study authors managed to do so. Image credit: Playbuzz.

This is the largest genetic study ever conducted and involved 105,000 individuals that consumed alcohol but were not addicted to it. All participants were European descendants and answered questionnaires on a weekly basis on drinking habits. The study was published Monday in the Proceedings of National Academy of Science.

The study found variations of the β-Klotho gene, which was linked to how much alcohol participants drank during the research. The gene is believed to be responsible for regulating drinking behavior. The gene’s less common variant has been associated with a decreased desire to consume alcoholic drinks. Less than 40 percent had the β-Klotho gene’s less frequent variant.

The FGF21 hormone is produced by the liver when it detects sugar and alcohol intake. It can also send a signal to the brain to reduce alcohol consumption, according to Professor Gunter Schumann from the Institute of Psychiatry, Psychology & Neuroscience at King’s College London.

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“Our study reveals a previously unrecognised liver-brain pathway which regulates alcohol consumption in humans, and which could one day be targeted therapeutically to suppress consumption in problem drinkers,” said Schumann.

β-Klotho gene and its role in alcohol drinking

Researchers studied the β-Klotho gene in mice to see if it affected alcohol drinking in the creatures. The efforts tried to understand what happens in the brain when the gene does its work. The research also measured how much alcohol mice drank, and it analyzed alcohol preference in mice that had the β-Klotho gene removed.

Mice lacking β-Klotho in the brain showed a significant increase in alcohol intake compared to those who did have the β-Klotho gene. Mice under normal conditions proved that the FGF21 hormone inhibits alcohol preference in them, while those which did not have the β-Klotho gene were not affected by the FGF21 liver hormone.

The results show that FGF21 effect on reducing alcohol consumption depends on the β-Klotho gene. Without it, the mice had the same drinking behavior than when they had not produced the hormone.

Professor Schuman stated that the β-Klotho could act by affecting neighboring genes. To rule out that possibility more studies are needed. Schuman added that the study on β-Klotho and FGF21 should be performed in people with more severe forms of alcohol consumption to better support their findings.

Professor Paul Elliott from the School of Public Health at Imperial, also involved in the study, said the results of the investigation stress the existence of a genetic determinant of alcohol drinking among the general population. The findings could lead to new treatments for alcoholism.

Source: Imperial College London