Ethyl alcohol, also known as ethanol, causes loss of balance and upright walking reflexes in mice. A new study, published this Tuesday in the journal cellular metabolismreveals that a hormone called fibroblast growth factor 21 (FGF21) protects these animals against symptoms of intoxication.
Alcohol inhibits the neurons that excite the brain and activates the ones that make it drowsy.
In the case of humans, it is not yet known how ethanol affects the body, as explained to SINC Steven Kliewer, from the Southwestern Medical Center of the University of Texas (USA) and lead author of the study. “Generally speaking, this chemical compound inhibits the neurons that excite the brain (glutamatergic neurons) and activates those that decrease brain activity (GABAergic neurons).”
“We discovered that the liver is not only involved in alcohol metabolism, but also sends a hormonal signal to the brain to protect it against the harmful effects of intoxication, including loss of consciousness and coordination”, says the biochemist.
The liver sends a hormonal signal to the brain to protect it from the harmful effects of alcohol.
Steven Kliewer, lead author
“We also showed that increasing levels of FGF21 by injection dramatically accelerates recovery. This hormone activates a very specific part of the brain that controls alertness,” says Kliewer. However, “it remains to be determined if and how this affects human neurons”, he emphasized in statements to SINC.
Ethyl alcohol can impair mobility and judgment
Consumption of ethanol produced by the natural fermentation of simple sugars in ripe fruits and nectars can cause intoxication and impair mobility and judgment. Animals that eat fructose and other simple sugars have developed liver enzymes to break down ethanol.
FGF21 is a protein that is induced in the liver by a number of metabolic stresses including starvation, protein deficiency, simple sugars and ethyl alcohol. In humans, ethanol is by far the most potent inducer of FGF21 described to date. Previous studies have shown that it suppresses ethanol preference, induces water intake to prevent dehydration, and protects against alcohol-induced liver damage.
The hormone counteracts alcoholic intoxication by activating the noradrenergic system. / Cell Metabolism.
The new study shows that this hormone “also has a number of metabolic benefits in mice, including weight loss, better insulin action, and improved cholesterol and triglyceride levels,” Kliewer describes. Furthermore, it plays a greater role than previously thought in defending against the deleterious consequences of ethanol exposure. FGF21 stimulated intoxication excitation without modifying ethanol degradation.
Mice without the hormone dose took longer to recover from alcohol intoxication
Mice lacking FGF21 took longer than their littermates to recover the right turn reflex and balance after exposure to ethanol. In contrast, pharmacological administration of the hormone reduced the time it took the mice to recover from alcohol-induced unconsciousness and muscle incoordination.
A specific hormone against ethanol
To the authors’ surprise, the injection did not compensate for the sedation caused by ketamine, diazepam or pentobarbital, indicating specificity for ethanol. FGF21 mediated its antitoxic effects by directly activating noradrenergic neurons in the locus coeruleus region of the brain, which regulate arousal and alertness.
The liver-brain pathway of the FGF21 hormone evolved to protect against ethanol-induced intoxication
The results suggest that the liver-brain FGF21 pathway evolved to protect against ethanol-induced intoxication. According to the researchers, this pathway can modulate various cognitive and emotional functions to improve survival under stressful conditions.
Ethanol also induces this protein and noradrenergic system activity in humans. However, further investigations are needed to determine whether the antitoxic function of FGF21 is also maintained. “In the meantime, the best advice remains to drink in moderation or not at all,” Kliewer advises SINC.
The best advice remains to drink in moderation or not drink at all.
“Our studies reveal that the brain is the main site of action of the effects of FGF21”, says David Mangelsdorf, also of the Southwestern Medical Center of the University of Texas and co-author of the article.
Whether activation of noradrenergic neurons contributes to the hormone’s other effects remains to be determined. “Now we are further exploring the neural pathways through which FGF21 exerts its inhibitory effect,” concludes Mangelsdorf.
Kliewer, S. et al. “FGF21 counteracts alcohol intoxication by activating the noradrenergic nervous system.” cellular metabolism (2023)