Why alcohol, sugar lead to thirst decoded

Scientists have identified a hormone that acts on the brain to stimulate thirst in response to sugar and alcohol, thereby preventing dehydration.

In the study, published in the journal Cell Metabolism, they found that the liver hormone or fibroblast growth factor 21 (FGF21) acts via the brain's reward pathway in mice to suppress the desire for sugar and alcohol in favour of drinking water.

"We knew that exposure to alcohol or sugar turns on production of FGF21 in the liver. What we now show is that this hormone then travels in the blood to a specific part of the brain, the hypothalamus, to stimulate thirst, thereby preventing dehydration," said Steven Kliewer from University of Texas Southwestern Medical Center in the US.

"Unexpectedly, FGF21 works through a new pathway that is independent of the classical renin-angiotensin-aldosterone thirst pathway in the kidneys," Kliewer said.

In mice, the hormone regulated hydration (water drinking) in response to nutrient stress.

The researchers found that normal mice and mice genetically unable to produce FGF21 drank similar amounts of water when given the typical chow diet.

However, a high-fat/low-carbohydrate ketogenic diet stimulated water drinking in normal mice while mice genetically unable to produce FGF21 failed to increase water intake in response to that nutritional stress.

Those findings confirmed the hormone's role in the signalling pathway, the researchers said.

A second important finding in this study is the very strong response to the hormone in humans.

For the study, 21 people were randomly assigned to drink either a mixture of alcohol and juice, or juice alone.

After four hours, the researchers measured their FGF21 blood levels. In response to alcohol, FGF21 levels peaked at around two hours and fell after that.

"This suggests that FGF21 might someday be used as a drug to limit alcohol consumption and protect against its effects in people," said David Mangelsdorf from University of Texas Southwestern Medical Center.

"Those findings also suggest that FGF21 is regulated the same way in humans as in mice and that the process involves the expression and activation of certain proteins in the brain," Mangelsdorf said.