Why Are Scientists Getting Mice Drunk?

4 min read

April 6, 2023 -- Paramedics or ER docs may someday revive dangerously drunk people by injecting them with a big dose of a liver hormone, according to researchers who saw promising results in mice.

It’s yet another indication that fibroblast growth factor 21 (FGF21), a liver-produced peptide hormone, can be a weapon in fighting various afflictions. Encouraging results have been seen in nonalcoholic fatty liver disease treatment, and scientists have also investigated potential benefits in weight loss and insulin control in humans.

In the newest study, severely “drunk” mice injected with FGF21 regained their balance and alertness more than twice as fast as those who didn’t get the shot. The scientists say the hormone stimulated the brain to release norepinephrine, a neurotransmitter that increases alertness.

If this reminds you of the naloxone spray used to counteract opioid overdoses, you’re not far off. 

“I would put it in the same kind of context, a little bit, as Narcan,” said study co-author David Mangelsdorf, PhD.

Mangelsdorf, the chair of pharmacology at the University of Texas Southwestern Medical Center, and his colleagues published their results in Cell Metabolism

The liver, which metabolizes alcohol, also produces FGF21 when stressed. The hormone stimulates a certain region of the brain to release norepinephrine, a neurotransmitter and also a hormone. It's a part of the body's "flight or flight" response, and as a neurotransmitter in your brain, helps to increase alertness and attention. In the study, mice that had been genetically modified to not produce norepinephrine had no response to FGF21.

In their experiments, researchers fed mice enough ethanol to knock them off their feet. Those given FGF21 shots were able to get back on their feet in 1 hour and 40 minutes, compared to 3 hours and 46 minutes in mice that didn’t receive FGF21. 

Mangelsdorf stressed that this would not be a cure, only a treatment in cases of severe alcohol poisoning, which can cause a fatal reduction in heart rate or breath rate. 

FGF21 could give patients just enough motor control and alertness to keep them from choking on their vomit or to simply tell doctors where it hurts. 

“A lot of times, these patients come in not because they’re drunk but because they’ve been injured in an accident,” Mangelsdorf said. 

Notably, while the mice regained some alertness and motor control after taking FGF21, their blood alcohol content remained unchanged. 

“This is not a party drug,” says study co-author Steven Kliewer, PhD, a professor of molecular biology at UT Southwestern. It wouldn’t sober you up or ease a hangover.

FGF21 only seems to counteract alcohol, not other types of sedatives. When the mice were dosed with ketamine, diazepam (also known as Valium), and phenobarbital (a barbiturate), the FGF21 shot had no effect.

Showing Promise in the Clinic

Like other hormones, FGF21 plays many roles. It has been shown to improve insulin sensitivity, stimulate weight loss, suppress the desire to drink alcohol, and even act as an antioxidant in the heart. 

Aside from being triggered by alcohol, the liver also produces FGF21 in response to a ketogenic, or keto, diet, low-protein diets, and consuming fructose, a sugar found in fruit. The hormone also stimulates thirst, and one prior study by Mangelsdorf and Kliewer found that when mice were put on a keto diet, the boost in FGF21 compelled the mice to drink 2.5 times as much water as mice that did not eat a keto diet. 

It's all likely a result of evolution, scientists say. An animal that accidentally eats fermented fruit can become drunk. 

“When you give alcohol to an animal, it drinks more water, and it’s a protective measure against the alcohol,” Mangelsdorf said. 

“This would be an important aspect that animals may have evolved to protect against alcohol,” he said, noting that a drunk animal would be easy prey or more likely to be injured.

In modern civilization, our natural FGF21 production is no match for margaritas and vodka spritzers. 

“This system didn’t evolve to deal with distilled spirits,” Kliewer said. “The pharmacologic doses we studied are roughly 1,000-fold higher than what would occur naturally.”

Researchers are also experimenting with FGF21 as a medication to treat alcoholism. Just last yearresearchers at the University of Iowa found that monkeys given a long-acting analogue of FGF21 drank 50% less alcohol over 25 days compared to monkeys that didn’t receive the treatment. 

And clinical trials are already underway to use FGF21 in humans to treat nonalcoholic steatohepatitis, or NASH, which is a type of fatty liver disease. 

“I think FGF21 analogues can be designed to be safely used in humans,” said Kyle Flippo, PhD, a postdoctoral researcher at the University of Iowa and the lead author of the alcohol consumption study. “I can’t say how long out that will be, but I think there is a very real possibility we will first see FGF21 used for treating NASH and then start being applied to diseases like alcohol use disorder.”

Flippo called for further research on whether FGF21 can restore both breathing rate and cognition before it can be counted on to treat alcohol poisoning. 

“That being said, the finding that an endogenous hormone can reverse the effects of ethanol intoxication on motor coordination is novel and significant,” Flippo said. 

Show Sources


David Mangelsdorf, PhD, chair of pharmacology, University of Texas Southwestern Medical Center.

Steven Kliewer, PhD, chair of developmental biology, University of Texas Southwestern Medical Center.

Kyle Flippo, PhD, postdoctoral researcher, University of Iowa.

Cell Metabolism: “FGF21 counteracts alcohol intoxication by activating the noradrenergic nervous system,” “The Hormone FGF21 Stimulates Water Drinking in Response to Ketogenic Diet and Alcohol,” “FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit.”

Annual Review of Physiology: “Understanding the Physiology of FGF21.”

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