Protein discovered that ‘turns off’ desire for alcohol

Researchers from the Beth Israel Deaconess Medical Centre have discovered a protective response in the liver that could be targeted to help treat alcoholic liver disease.

The finding involves a protein called fibroblast growth factor 21 (FGF21), which was previously found to help protect mice against diet-related toxicities to the liver.

Increasing levels of the protein – in lab mice – caused them to prefer water over alcohol.

The same protective response may be involved in aversion to alcohol and could therefore be utilised in the treatment of alcoholism.

The study’s co-senior author, Eleftheria Maratos-Flier, said: ‘Looking at the relationship between alcohol-induced liver disease and FGF21 was the next step.’

‘We showed that alcohol consumption induces FGF21 as a protective response in the liver that reduces the degree of alcohol-induced damage,” said Maratos-Flier. “Because humans and mice have similar responses, mice may be a good model for studying this further.’

The study, which has been published in the journal Molecular Metabolism, found that people who binged on alcohol over a one-hour period exhibited massive increases of FGF21 in their blood six hours later. Similar results were seen in mice. Also, in mice bred to lack FGF21, binging on alcohol led to more liver damage than that seen in wild mice, along with an increased expression of genes involved in inflammation and scarring in the liver.

Alcohol was cleared normally in mice lacking FGF21, suggesting that FGF21 does not play a role in acute alcohol metabolism. Also, mice that were bred to overexpress FGF21 consumed less alcohol than wild mice. A similar effect was observed when wild mice were administered extra FGF21.

The findings suggest that the protein has a dual role in alcohol metabolism. The rise in FGF21 in response to alcohol consumption seems to inhibit further drinking. Simultaneously the rise in FGF21 expression in the liver may protect against liver damage.

‘Our results may encourage the development of drugs that mimic FGF21 for the treatment of alcoholic liver disease, and possibly to produce alcohol aversion,’ Maratos-Flier said.