A hormone that helps drunken mice sober up could one day treat acute alcohol poisoning in people.
The livers of mice and people produce the hormone FGF21, which is known to interact with parts of the brain. Previous research suggests that alcohol use is the biggest trigger for the production of FGF21 in people, reducing our appetite for alcohol and protecting our liver from alcohol-induced injury. Variations in the genes for FGF21 and its receptor can affect the amount of alcohol we consume.
steven kliewer other david mangelsdorf at the University of Texas Southwestern Medical Center and his team were studying FGF21 when they discovered that mice that cannot produce the hormone take twice as long to regain consciousness after receiving an intoxicating dose of ethanol, the form of alcohol in beverages. , compared to their FGF21-producing counterparts.
To learn more, the team gave mice that produced normal amounts of FGF21 an intoxicating dose of ethanol. The animals were then injected with more hormones.
Compared to mice that did not receive this injection, these animals took half as long to wake up and get to their feet after being knocked out by the ethanol. They also regained their coordination faster.
“We know how important the liver is in terms of breaking down ethanol, but here’s this completely new pathway where the liver sends a distress signal to the brain to mitigate the effects of intoxication,” says Kliewer.
The researchers also found that in mice, FGF21 acts on neurons in a region of the brain called the locus coeruleus, which produces the neurotransmitter norepinephrine. This region controls sleep alertness and arousal.
In people, drinking alcohol increases the amount of norepinephrine produced by the brain. This may occur via FGF21, which would suggest that administering it could similarly help drunk people sober up, Kliewer says.
While more research is required, an injection of FGF21 could be given to people who come to the hospital with acute alcohol poisoning. Once conscious and coherent, doctors could interrogate and treat them faster.
Elsewhere in the experiment, FGF21 had no effect on the mice’s ability to recover from sedation with drugs such as ketamine, suggesting that the hormone’s sobering effect is alcohol-specific. “It means that there are specific neurons in that center of the brain that are probably involved in different responses to different situations,” says Mangelsdorf.
According matthew guillumstudying FGF21 at the pharmaceutical company Novo Nordisk in Denmark, the findings deepen our growing understanding of the relationship between the hormone and alcohol use.