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Liver-derived hormone FGF21 dramatically reduces appetite for alcohol Researchers believe that humans first encountered alcohol long before we learnt how to control the process and make it ourselves – through the consumption of fermented fruit. One plausible result of this long history of alcohol exposure is that we have evolved a suite of biological mechanisms for detoxifying and regulating our appetite for alcohol, which may be useful for developing new treatments for alcohol use disorder. Now, a recent randomized controlled trial suggests that the liver-derived hormone fibroblast growth factor 21 (FGF21) is a candidate treatment capable of altering the reward system of the brain and profoundly reducing alcohol intake in primates.

The researchers carried out their study in vervet monkeys – a species that parallels human populations in containing a mix of alcohol avoiders, moderate consumers, and heavy consumers who will drink to the point of intoxication. Twenty monkeys were selected based on having at least a slight interest in consuming alcohol. The researchers then quantified each individual’s preferred alcohol intake level by monitoring their behaviours when the animals received four hours of daily access to a bottle of 10% ethanol solution alongside plain tap water.

After a baseline observation period of nine days, monkeys were randomly selected to receive a daily injection of either a sterile saline solution (placebo) or a pharmacological analog of the liver hormone FGF21 for a total of 16 days.

The FGF21-mimicking drug was found to produce a 50 percent reduction in alcohol consumption, without influencing the monkeys’ intakes of food or water. Looking into the effects of FGF21 in the brain, the researchers uncovered that both FGF21 and its synthetic analog increased the transmission of signals to a specific group of brain cells in the nucleus accumbens – a hotspot of the brain’s reward system. These cells were distinguished by the presence of specifically D2-type dopamine receptors, which have been strongly implicated in reigning in impulsive and repetitive consumption of other substances like sugar. Human variants in the D2 receptor gene have also been linked to greater risk of alcohol dependence.

The findings suggest that FGF21 serves as a regulatory message between the liver and the brain’s impulse control circuits, and that boosting this signal may aid in the treatment of substance addictions.

-Link to full publication.

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