The human body is a greedy thing, having evolved a large number of reward pathways related to the consumption of high-calorie, high-fat, and high-sugar foods. This was fine when we were hunting and gathering, but for a lot of us the energy required to obtain those foods has been reduced to almost nil. Our bodies just haven’t figured that out yet. However, a team of researchers from the University of Texas Southwestern Medical Center may have found a liver hormone that can help curb those cravings.

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.

 








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