US researchers say that giving mice an injection of a hormone can keep them from losing their balance after drinking. Researchers found that intoxicated mice injected with more of the hormone fibroblast growth factor 21 (FGF21) recovered from their inebriation more quickly than their sober littermates.
A new study published today in the journal Cell Metabolism found that the hormone fibroblast growth factor 21 (FGF21) shields mice from the loss of balance and righting reflex caused by ethanol.
“We’ve discovered that the liver is not only involved in metabolizing alcohol,” explains Co-senior study author Steven Kliewer, “but that it also sends a hormonal signal to the brain to protect against the harmful effects of intoxication, including both loss of consciousness and coordination.
Moreover, they demonstrated that by boosting FGF21 concentrations via injection to even higher levels, we may significantly expedite recovery from intoxication.
“FGF21 does this by activating a very specific part of the brain that controls alertness,” adds Kliewer.
When you drink ethanol, which is made by the natural fermentation of simple sugars in ripening fruits and nectars, you can get drunk and lose control of your body and mind. Animals that ingest simple sugars like fructose and others have developed liver enzymes that can break down alcohol.
FGF21 is a hormone that is activated in the liver by a number of metabolic stressors, including protein shortage, simple carbohydrates, ethanol, and starvation. Ethanol is by far the most effective inducer of FGF21 in humans that has been identified so far.
According to previous studies, FGF21 reduces ethanol desire, promotes water consumption to stave off dehydration, and guards the liver against damage brought on by alcohol.
In the current work, Kliewer and co-senior author David Mangelsdorf of the University of Texas Southwestern Medical Center demonstrate that FGF21 plays a larger role than previously believed in protecting against the harmful effects of ethanol consumption.
FGF21 increased intoxication-induced alertness in mice without affecting the breakdown of ethanol. Mice without FGF21 took longer than their littermates to get their balance and righting reflex back after being exposed to ethanol.
Pharmacologic FGF21 treatment, on the other hand, shortened the time required for mice to recover from ethanol-induced unconsciousness and loss of muscular coordination.
Surprisingly, FGF21 didn’t stop ketamine, diazepam, or pentobarbital from making people sleepy. This shows that it only works against ethanol.
FGF21 mediated its anti-intoxicant actions by directly stimulating noradrenergic neurons in the brain area that controls arousal and alertness, the locus coeruleus.
When all the results are looked at together, they suggest that the FGF21 liver-brain pathway evolved to protect against getting drunk from ethanol.
The authors say that this pathway may change a number of cognitive and emotional functions to help people stay alive in stressful situations.
It is yet unknown if stimulation of the noradrenergic system contributes to FGF21’s other effects, such as those on metabolism, ethanol tolerance, and sweet tooth.
Even though ethanol makes both FGF21 and the noradrenergic nervous system work in humans, more research will be needed to see if FGF21’s anti-intoxicant effect also works in humans.
“Our studies reveal that the brain is the major site of action for FGF21’s effects,” Mangelsdorf adds. “We are now exploring in greater depth the neuronal pathways by which FGF21 exerts its sobering effect.”
Source: 10.1016/j.cmet.2023.02.005
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