April 6, 2023 – Paramedics or emergency doctors may someday give you the chance to revive dangerously drunk people by injecting them with a big dose of a liver hormone, based on researchers who’ve observed promising leads to mice.
This is further evidence that fibroblast growth factor 21 (FGF21), a peptide hormone produced by the liver, could also be a weapon within the fight against various ailments. Encouraging results have been seen within the treatment of non-alcoholic fatty liver disease, and scientists have also studied possible advantages in weight reduction and insulin control in humans.
In the newest study, heavily “drunk” mice injected with FGF21 regained their balance and application greater than twice as fast as mice that didn't get the shot. The scientists say the hormone stimulates the brain to release norepinephrine, a neurotransmitter that increases alertness.
If this reminds you of the naloxone spray used to treat an opioid overdose, you should not mistaken.
“I would put it in a little bit the same context as Narcan,” said study co-author Dr. David Mangelsdorf.
Mangelsdorf, chair of pharmacology on the University of Texas Southwestern Medical Center, and his colleagues published their leads to Cell metabolism.
The liver, which metabolizes alcohol, also produces FGF21 during stress. The hormone stimulates a certain region of the brain to release noradrenaline, a Neurotransmitter and also a hormone. It is a component of the body's “fight or flight” response and acts as a neurotransmitter within the brain to extend alertness and a spotlight. In the study, mice that had been genetically modified to not produce norepinephrine didn’t reply to FGF21.
In their experiments, the researchers gave mice a lot ethanol that they fell over. The mice that got FGF21 injections were in a position to get back on their feet after 1 hour and 40 minutes, while mice that weren’t given FGF21 took 3 hours and 46 minutes.
Mangelsdorf emphasized that this just isn’t a cure, but merely a treatment for severe alcohol poisoning, which may result in a fatal slowing of the guts or respiratory rate.
FGF21 could give patients barely enough motor control and application to stop them from choking on their vomit or to easily tell doctors where it hurts.
“Often these patients do not come because they are drunk, but because they were injured in an accident,” said Mangelsdorf.
Notably, although the mice regained some attention and motor control after taking FGF21, their blood alcohol levels remained unchanged.
“It's not a party drug,” says study co-author Steven Kliewer, PhD, a professor of molecular biology at UT Southwestern. It won't sober you up or cure a hangover.
FGF21 only seems to counteract alcohol, not other kinds of tranquilizers. When mice got ketamine, diazepam (also referred to as Valium), and phenobarbital (a barbiturate), the FGF21 shot had no effect.
Promising leads to the clinic
Like other hormones, FGF21 plays many roles. It has been shown to enhance insulin sensitivity, stimulate weight reduction, suppress alcohol cravings, and even acts as an antioxidant in the guts.
Aside from being triggered by alcohol, the liver also produces FGF21 in response to a ketogenic or keto weight-reduction plan, a low-protein weight-reduction plan, and the consumption of fructose, a sugar present in fruit. The hormone also stimulates thirst and a previous study von Mangelsdorf and Kliewer found that mice placed on a keto weight-reduction plan needed to drink 2.5 times as much water as mice not on a keto weight-reduction plan on account of increased FGF21 concentration.
The whole thing might be a results of evolution, scientists say. An animal that unintentionally eats fermented fruit can turn out to be drunk.
“If you give an animal alcohol, it drinks more water and it is a protective measure against the alcohol,” said Mangelsdorf.
“This would be an important aspect of why animals may have evolved to defend themselves against alcohol,” he said, declaring that a drunk animal could be easy prey or more prone to be injured.
In modern civilization, our natural FGF21 production isn’t any comparison to margaritas and vodka spritzers.
“This system is not designed to process spirits,” Kliewer said. “The pharmacological doses we studied are about 1,000 times higher than what would occur naturally.”
Researchers are also experimenting with FGF21 as a drug to treat alcoholism. Only last year, Researchers on the University of Iowa found that monkeys given a long-acting analogue of FGF21 drank 50% less alcohol over a 25-day period than monkeys that didn’t receive this treatment.
And clinical trials There are already studies on using FGF21 in humans to treat non-alcoholic steatohepatitis (NASH), a type of fatty liver disease.
“I think FGF21 analogues can be developed to a point where they can be safely used in humans,” said Dr. Kyle Flippo, a postdoctoral fellow on the University of Iowa and lead writer of the alcohol use study. “I can't say how long that will take, but I think there's a very real possibility that FGF21 will be used first to treat NASH and then also for diseases like alcohol abuse.”
Flippo called for further research into whether FGF21 can restore each respiratory rate and cognitive abilities before it may be relied upon to treat alcohol poisoning.
“Nevertheless, the discovery that an endogenous hormone can reverse the effects of ethanol intoxication on motor coordination is novel and significant,” Flippo said.