A hormone produced in the liver of mammals has been shown to prevent monkeys from overindulging in alcohol. Intriguingly, the same molecule lowers consumption of both alcohol and sugar in mice, but acts on separate brain circuits to do so. Modern mass epidemiological studies have sadly revealed the damage parts of our diet are doing to us, but the demon drink has been marked as a problem for millennia. Religions have proscribed it, nations have banned it with heavy penalties, and a thousand techniques have been developed to help those too fond of the bottle for their own good kick the habit. Success rates have ranged from poor to non-existant, but perhaps the answer has lain within us all along – not willpower, but the hormone fibroblast growth factor 21 (FGF21). Dr Matthew Potthoff of the University of Iowa is part of a large international team that administered an FGF21 analog to vervet monkeys who, untreated, prefer ethanol to water when offered both. In Cell Metabolism, Potthoff and coauthors report the monkeys given the hormone drank half as much alcohol as their untreated counterparts. After the treatment stopped the two groups converged over the subsequent fortnight. Animal studies don't always translate to humans, particularly on something like alcoholism, where social circumstances can be just as important as biological effects. Nevertheless, this is just one piece of evidence that FGF21 might influence our drinking habits. Genome-Wide Association Studies have found people with unusual variants of the gene responsible for FGF21 production are more likely to drink heavily. Alcohol consumption goes deep in our evolutionary past, as stories of various animals drunk on fermented fruit demonstrate. “Given that excessive alcohol consumption negatively impacts health and survival, it is not surprising that numerous physiological systems have evolved to send and regulation alcohol consumption in mammals,” the paper notes. Producing FGF21 appears to be the liver's way of fighting back, telling the brain it's had enough. Previous work had already shown FGF21 administration can increase sobriety in rodents, and Potthoff and co-authors reported in an earlier study it also reduced sugar intake in mice. When studying the brains of their subjects the team found the hormone affects the activity of a subpopulation of neurons in the nucleus accumbens, suppressing alcohol consumption. They confirmed this by using optogenetics to manipulate the responses of these specific neurons. However, when it comes to stopping mice from hitting the sugar so hard the effect is on a different part of the brain's reward-seeking system. “Neural circuits regulating FGF21-mediated suppression of sugar and alcohol intake apparently developed independently and not in response to a shared selective pressure,” Potthoff noted in a statement. “Our results provide a mechanism for a liver-to-brain endocrine feedback loop that presumably functions to protect the liver from damage,” co-author Dr Kyle Flippo said. “The central molecular and cellular effects of FGF21 represent an opportunity for future research, and the present data indicates that FGF21 analogues may provide a potential treatment option against alcohol-use disorder and related diagnosis.” Source
