Rare sugars activate metabolic signaling to reduce alcohol consumption in mice

While investigating the FGF21-oxytocin-dopamine system, a mechanism that regulates sugar appetite, a team of researchers at Kyoto University noticed reports suggesting that the protein FGF21 may regulate alcohol ingestion. The team's original aim had been to address sugar appetite in lifestyle-related diseases, but since alcohol is a fermented product of sugar, they speculated that perhaps the body contains a system that recognizes both alcohol and sugar as the same entity.

Excessive alcohol consumption is a major global health issue, and effective countermeasures for prevention and treatment are limited. Patients with alcohol dependence generally have a low adherence to pharmaceuticals, and many avoid drug treatment because it deprives them of the pleasure of drinking.

"It was important that any intervention provide pleasure and act as a substitute for alcohol," says corresponding author Sho Matsui. "We imagined that some functional sugars may be able to fill that role."

To investigate their theory, the research team developed a new protocol to model alcoholism in mice. They then used different FGF21-inducing food ingredients to test how they affect the behavior of the mice toward alcohol.

The team observed that the FGF21-oxytocin-dopamine system serves as a replete signal for alcohol intake, but that this system was down-regulated in the alcohol-dependent mice, causing them to over-drink. By stimulating the system with FGF21-inducing food ingredients, namely rare sugars, the researchers were able to reduce alcohol consumption in both healthy and alcohol-dependent mice.

These results demonstrate that alcohol dependence may exist not only as a disease of substance abuse, but could also be caused by the dysregulation of subconscious information processing mediated by the FGF21 metabolic signal in the central nervous system. Therefore, tweaking the FGF21-oxytocin-dopamine system with functional dietary ingredients may prove effective in regulating alcohol consumption.

"Dietary therapy is effective in controlling appetite if you can stick to it, but most can't. The same applies to over-drinking," says team leader Tsutomu Sasaki. "Our work demonstrates that there is a subconscious inter-organ crosstalk signal that regulates appetite for alcohol."

Next, the team would like to confirm these findings in humans and to develop foods and beverages that help to reduce alcohol consumption. Such treatment may be provided in forms of dietary supplements, nutraceuticals, and non-alcoholic beverages, and the team is also working on developing a potent FGF21-inducer drug.

Source:

Kyoto University

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