Liver hormone may help reduce alcohol addiction
Researchers have pieced together a more complete picture of the role that a particular hormone plays in alcohol addiction. Monkeys with a strong alcohol preference drank far less after they were given a synthetic version of this hormone, potentially opening the path to new treatments for alcohol addiction.
The hormone in question is known as fibroblast growth factor 21 (FGF21), and it’s produced by the liver. Previous work has shown that variants in genes associated with FGF21 are linked to increased alcohol consumption in humans, but the exact nature of that link remained uncertain. So for the new study, researchers investigated which brain circuits FGF21 is affecting, and whether administering the hormone could reduce the desire for alcohol.
The team tested the idea in vervet monkeys, whose attitude to alcohol is remarkably similar to humans. In monkey communities with access to alcohol – either naturally fermenting fruit or unsupervised drinks in tourist hotspots – most animals are social drinkers, while some abstain, and a small percentage are binge drinkers. This last group was the subject of the study.
The researchers gave the monkeys a two-bottle choice between water and ethanol, and administered one group an analog of FGF21 to see what effect it had. Sure enough, the test monkeys drank 50 percent less alcohol than the control group. Similar tests in mice also saw a 50-percent reduction in alcohol consumption after being given either human FGF21 or an analog. Interestingly though, the mice and monkeys still chose the ethanol just as often as before, but they drank far less each time.
Next, the researchers investigated where FGF21 functions in the brains of mice. They found that the hormone changes the activity of a subpopulation of neurons in the basolateral amygdala. This in turn affects neural transmission to the nucleus accumbens, a brain region that’s known to play a role in reward functions and addiction.
When an animal drinks alcohol, the liver produces higher levels of FGF21, which works to suppress the desire for further alcohol intake. This is why individuals with FGF21 gene variations may drink more, and also why the animals in the experiments still sought out alcohol initially but drank less of it in each sitting.
The researchers say that this mechanism may have evolved to protect animals from the health dangers of excessive alcohol consumption. Interestingly, the team previously linked FGF21 to a similar suppression of sugar consumption, although that works on a completely different part of the brain.
“When considering how and why these modality specific mechanisms evolved, it is interesting to note that mammals were primarily exposed to alcohol from fermenting fruits, which possess high levels of simple sugars,” said Matthew Potthoff, senior author of the study. “Despite this, neural circuits regulating FGF21-mediated suppression of sugar and alcohol intake apparently developed independently and not in response to a shared selective pressure.”
The team says that FGF21 analogs could eventually be developed into potential treatments for alcohol addiction, but far more work will need to be done in the meantime.
The research was published in the journal Cell Metabolism.