According to a research published in the journal Cell Metabolism on February 1, a hormone generated by the liver termed fibroblast growth factor 21 (FGF21) reduces alcohol intake in monkeys. When given a FGF21 counterpart, vervet monkeys with a high affinity for ethanol ingested 50% less alcohol. The researchers looked at the brain circuits in mice and discovered that the protein, which is also known to lower sugar intake, operates on separate circuits to reduce alcohol and sugar consumption.
“When considering how and why these modality-specific mechanisms evolved,” says senior study author Matthew Potthoff of the University of Iowa Carver College of Medicine, “it’s interesting to note that mammals were primarily exposed to alcohol from fermenting fruits, which contain high levels of simple sugars.” “Despite this, neuronal circuits governing FGF21-mediated sugar and alcohol intake suppression seem to have evolved independently of one another, rather than in response to a similar selection pressure.”
In contemporary culture, excessive alcohol intake is a huge health and social problem. Given the harmful effects of excessive alcohol use on health and survival in animals, it’s not unexpected that a variety of physiological mechanisms have developed to detect and manage it. Unfortunately, therapeutic targeting of circuits that govern alcohol intake has shown to be ineffective in treating alcohol use disorder.
FGF21 genetic variations have recently been associated to greater alcohol use in humans, according to genome-wide association studies. Pharmacologic treatment of this liver-produced protein decreases alcohol intake in animals through brain-based mechanisms. However, the neuronal circuits via which FGF21 reduces alcohol intake, as well as its effects on alcohol consumption in higher species, were unclear until today.
Potthoff and co-first author Kyle Flippo of the University of Iowa, as well as international collaborators including co-first authors Drs. Matthew Gillum and Samuel Trammell of the University of Copenhagen, demonstrated that giving a FGF21 analogue to vervet monkeys with a strong innate preference for ethanol reduces alcohol intake by 50%. Even when given after extensive ethanol exposure, FGF21 and its counterpart reduce alcohol consumption in mice and primates.
FGF21 affects neuronal transmission in the nucleus accumbens, a brain area involved in reward and addiction, and inhibits alcohol intake through a subpopulation of neurons in the basolateral amygdala. FGF21 signaling in neurons that extend from the basolateral amygdala to the nucleus accumbens, in particular, decreases alcohol intake by altering the activity of a subset of these neurons. This route has been linked to reward-seeking behavior in previous research. More study is required, according to the scientists, to determine the exact effects of FGF21 on the activity of these neurons following alcohol intake in animal models.
“Our findings suggest a mechanism for a liver-to-brain endocrine feedback loop that protects the liver from harm,” adds Flippo. “FGF21 analogues may give a possible therapy option against alcohol-use disorder and associated diagnoses, and the current evidence shows that FGF21 analogues may provide a potential treatment option against alcohol-use disorder and related diagnoses.”