Liver Hormone Regulates Sweet & Alcohol Preferences

    A hormone found in the liver has the ability to reduce sweet and alcohol cravings in mammals, a recent study found.

    UT Southwestern Medical Center researchers found the hormone, fibroblast growth factor 21, works through the brain’s reward system to weaken cravings. It is induced in the body by extreme cold temperatures, sudden changes in diet and in carbohydrate consumption.

    This hormone, fibroblast growth factor 21 (FGF21), is produced when the body is in distress, resulting from major dietary changes or drastic environmental factors—even cold weather exposure. (When it snows, why do so many of us reach for creamy hot cocoa?) Incidentally, FGF21 production in mammals also steps up after consuming carbohydrates, making it a handy metric to evaluate various protein structures for usefulness in treating Type 2 diabetes and obesity.

    When mice with elevated FGF21 production were given water with added sugar and alcohol, they exhibited a significantly reduced preference for the carb-rich drinks, as well as decreased dopamine response. In larger mammals, controlling the flow of FGF21 could mean reducing the craving for, and dependence on, alcohol—a reaction with incredible potential for treating addiction.

    Dr. Steven Kliewer, Ph.D., one of the lead researchers on the project, says that “findings raise the possibility that FGF21 administration could affect nutrient preference and other reward behaviors in humans, and that the hormone could potentially be used to treat alcoholism.”

    The study, published in the journal Cell Metabolism, is the fourth study on FGF21 for the team co-headed by Dr. David Mangelsdorf, Ph.D. Their three previous studies have shown how the hormone can interact directly with the central nervous system to help regulate metabolism and circadian rhythms.  The degree of interaction also has an effect on weight loss and female reproduction.

    For each of these experiments, the presence of membrane protein β-Klotho co-receptors was used as a basis for comparison to a control group. FGF21 needs to bind with β-Klotho to be rendered effective. Mice used in this study that were unable to produce β-Klotho naturally, which were then introduced to the FGF21 hormone, showed no change in taste preference or carbohydrate consumption.

    “The finding that FGF21 acts via the brain was completely unexpected when we started down this path of investigation a dozen years ago,” Dr. Kliewer said. “These findings suggest that additional studies are warranted to assess the effects of FGF21 on sweet and alcohol preference and other reward behavior in humans.” Perhaps in coming years those New Year’s resolutions may not be quite so hard to keep.