For thousands of years, people have been searching for an antidote to consuming too much alcohol — an intervention that could accelerate the sobering process. Ancient Greeks drank from amethyst chalices because they believed it would help reduce drunkenness. People continue to use modern remedies, such as coffee, cold showers, and food. Although these may help with alertness and hunger, only pumping the stomach to remove undigested alcohol from the body and time can currently reverse the effects of intoxication. New research in mice suggests that a hormone produced in the liver could eventually be developed into a drug to treat acute alcohol poisoning and potentially save lives.
“Humans have long searched for agents that could reverse drunkenness, and now we have discovered something to achieve this effect that’s been in our bodies the whole time,” said David Mangelsdorf, Professor of Pharmacology and Biochemistry at the University of Texas Southwestern (UTSW) Medical Center. The research effort was co-led by Mangelsdorf and UTSW colleagues Steven Kliewer, Professor of Molecular Biology and Pharmacology, and Mihwa Choi, Instructor of Pharmacology.
Speeding Up Sobering
The research results, published in Cell Metabolism, demonstrate the accelerated sobering effects of the hormone known as fibroblast growth factor 21 (FGF21). For one study, researchers evaluated the effects among mice that had consumed enough alcohol to induce unconsciousness, simulating binge drinking. Compared to the control group, animals injected with FGF21 regained consciousness and were able to stand upright in about half the time. For another part of the study, mice received smaller doses of alcohol to mimic typical human consumption and induce a reduced level of coordination. Mice that then received the FGF21 injections recovered from the alcohol’s effects more rapidly than the control group.
The two groups of mice had the same blood alcohol concentrations, suggesting that the intervention did not influence alcohol metabolism. Likewise, FGF21 did not accelerate a return to alertness when the mice were given alternative drugs such as ketamine, diazepam, or pentobarbital, indicating a specificity to alcohol.
How Does It Work?
The liver produces FGF21 in response to a variety of metabolic stresses, including starvation, protein deficiency, simple sugars, and ethanol. “In humans, ethanol is by far the most potent inducer of FGF21 described to date,” the researchers reported. They noted that previous research in mice has demonstrated that FGF21 suppresses alcohol preference, induces water consumption to prevent dehydration, and protects against alcohol-induced liver injury.
In the current study, the researchers traced the anti-intoxicant effects of the hormone to the liver-brain pathway. They determined that FGF21 directly activates neurons that release norepinephrine (NE) in the locus coeruleus region in the brain, regulating arousal and alertness. “Taken together, this work reveals that FGF21 is an endogenous, ethanol-selective amethystic agent that complements the liver’s alcohol metabolizing enzymes in defending against ethanol toxicity and its potentially dangerous sequelae,” the authors concluded. The researchers speculated that the FGF21 pathway evolved to protect against alcohol intoxication and to heighten arousal and alertness for increased foraging during periods of nutritional deficiency. “Thus, the FGF21-NE pathway may modulate a variety of cognitive and affective functions to enhance survival under stressful conditions,” they continued.
Next Steps
Additional research is necessary to determine whether FGF21’s anti-intoxicant activity translates to humans. Human FGF21 analogs have been created and evaluated in clinical trials for metabolic disorders including type 2 diabetes, obesity, and nonalcoholic fatty liver disease. Someday, an FGF21 drug could be developed to treat acute alcohol poisoning in emergency rooms, on college campuses, and other settings, similar to how Narcan is used to treat opiate overdoses.
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