Tuesday, May 15, 2018 by Ralph Flores
Not all drinks were made to quench a person’s thirst: Far from it, alcoholic beverages and those that contain sugar make us even thirstier, and scientists may have found the reason why. In a study published in Cell Metabolism, research indicated the liver hormone FGF21, or fibroblast growth factor 21, to be responsible for the brain’s actions to increase water intake to prevent dehydration.
Researchers from the University of Texas Southwestern Medical Center (UT Southwestern) have been studying FGF21 for a long time, with earlier research pointing out the hormone’s ability to act using the brain’s reward pathway to control the need for sugar and alcohol in favor 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,” explained Dr. Steven Kliewer, a professor at UT Southwestern. “Unexpectedly, FGF21 works through a new pathway that is independent of the classical renin-angiotensin-aldosterone thirst pathway in the kidneys.”
In the study, the team discovered that FGF21 regulated hydration in response to nutrient stress. Using both healthy mice and those that were mutated to be genetically unable to produce FGF21, they discovered that while both mice were able to drink similar amounts of water after a standard diet, the mutated mice were unable to produce FGF21 after they were subjected to a high-fat/low-carbohydrate ketogenic diet. According to researchers, this established the role of the hormone in the signaling pathway.
The team also looked at how FGF21 responds in humans in a clinical trial at the Medical University of Graz in Austria. In the trial, a total of 21 participants were assigned to drink either a mixture of alcohol and juice or a mixture of juice alone. After drinking, researchers measured their FGF21 levels in their blood in hourly intervals over four hours. Based on the results, FGF21 peaked in response to alcohol two hours after consumption, then fell afterward.
“This suggests that FGF21 might someday be used as a drug to limit alcohol consumption and protect against its effects in people,” UT Southwestern’s Dr. David Mangelsdorf added. “[These] 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.”
However, researchers pointed out that the response following FGF21 induced thirst may rely on another signaling pathway called the β-adrenergic circuit. According to Mangelsdorf, earlier studies have hinted at this pathway to regulate thirst; data in the current research also supports this theory.
The results of the study, the researchers said, could change how feeding behavior is studied. Currently, the focus of behavior has been on metabolic behavior, instead of hydration.
“To put this in context, we always look at food intake, and the metabolic field has spent comparatively little time studying water intake,” Kliewer added. “This study suggests that we should think more about hydration and how it might contribute to metabolism.” (Related: Alcohol – not marijuana – is the gateway drug, study shows.)
In a separate study, researchers from the University of Exeter in the U.K. and the University of Copenhagen in Denmark have found that a genetic variation of FGF21, which they called the “A version,” is linked to lower body fat. However, this also made them prone to cravings and eat more sugar than others.
“We were surprised that the version of the gene associated with eating more sugar is associated with lower body fat. It may reduce body fat because the same allele also results in a lower consumption of protein and fat in the diet,” added Timothy Frayling, the study’s first author and a molecular geneticist at the University of Exeter Medical School.
Still, people with this genetic variant have their fair share of complications: Researchers said that A version is also linked to a rise in blood pressure and the development of an apple-shaped body.
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