This past December, two research teams independently made the same discovery: A hormone that originates primarily in the liver might be responsible for regulating both sugar and alcohol-cravings.
FGF21: A liver hormone that reduces cravings
The first study examined how fibroblast growth factor 21 (or FGF21) impacted nutrient preference in mice and monkeys. FGF21 is a hormone made in the liver that is involved in metabolic processes or — in more straight-forward terms — converting food into energy. In humans, high levels of FGF21 are associated with obesity, Type 2 diabetes, coronary artery disease and other conditions associated with poor diet.
In this study, the scientists administered FGF21 to mice and cynomolgus monkeys. After receiving the hormone, both the mice and the monkeys demonstrated a markedly reduced preference for sweet food. In addition, the mice (but not the monkeys) grew significantly less interested in alcohol.
When the scientists examined the brains of the mice, they found reduced concentrations of dopamine — a neurotransmitter associated with positive mood — in the reward center of the brain. Since the reward center tends to become activated when a person (or, in this case, a mouse) experiences a good meal, a good lover or a good alcoholic drink, the loss of dopamine suggests that the activity in question has become less pleasurable. In other words, mice who received FGF21 found sugar and alcohol less rewarding. Monkeys, on the other hand, found sugar — but not alcohol — less rewarding.
According to the authors, this is the first liver-derived hormone known to reduce sugar (and sometimes alcohol) preference.
“Since analogs of FGF21 are currently undergoing clinical evaluation for the treatment of obesity and Type 2 diabetes, our findings raise the possibility that FGF21 administration could affect nutrient preference and other reward behaviors in humans,” explained the study’s authors, led by Steven A. Kliewer, Ph.D., and David J Mangelsdorf, Ph.D., both with the University of Texas Southwestern Medical Center.
How FGF21 reduces cravings
The second study examined why the liver produces FGF21 and precisely how it impacts cravings. When they investigated FGF21 production in mice, they found that the liver produces the hormone in response to sugar intake. After the mouse consumes sugar, FGF21 enters the bloodstream and communicates with the hypothalamus. In mammals, the hypothalamus is responsible for regulating the behavior necessary for the four F’s: fighting, fleeing, feeding and fornicating. The scientists suspect that FGF21 alters activity within the hypothalamus and shifts feeding behavior, making the animal less interested in sugar.
“We never imagined that a circulating, liver-derived factor would exist whose function is to control sweet appetite,” explained Matthew P. Gillum, Ph.D., with the University of Copenhagen, who led a group of scientists with Matthew J. Potthoff, Ph.D., with the University of Iowa Carver College of Medicine. “We are very excited about investigating this hormonal pathway further.”
What this discovery means for fighting obesity and alcoholism
It’s (understandably) tempting to think that manipulating the FGF21-regulated pathway might be enough to effectively “turn off” sugar and alcohol cravings. After all, the first study shows that FGF21 impacts the brain’s reward center, a vital part of the addiction circuit, and the second study shows that FGF21 alters activity within the hypothalamus, yet another region associated with habitual behavior. In both studies, animals that were given FGF21 lost interest in sugar, and in one study, the animals lost interest in alcohol as well.
Unfortunately, the answers in neuroscience are rarely that simple. What if FGF21 can’t actually influence the human brain? What if receiving FGF21 injections doesn’t just erase your cravings for sugar and alcohol, but also your cravings for healthy things like exercise and sleep?
One thing is for certain — scientists will continue to investigate FGF21 as a potential treatment for obesity and alcoholism. Time will only tell if it works.
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Written by Courtney Lopresti, M.S. neuroscience, Sovereign Health Group writer
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