Few pleasures compare to a long cool drink on a hot day. As a glass of water or other tasty drink makes its way to your digestive tract, your brain is tracking it — but how? Scientists have known for some time that thirst is controlled by neurons that send an alert to put down the glass when the right amount has been guzzled. What precisely tells them that it is time, though, is still a bit mysterious.
In an earlier study, a team of researchers found that the act of gulping a liquid — really anything from water to oil — is enough to trigger a temporary shutdown of thirst. But they knew that gulping was not the only source of satisfaction. There were signals that shut down thirst coming from deeper within the body.
In a paper published Wednesday in Nature, scientists from the same lab report that they’ve followed the signals down the neck, through one of the body’s most important nerves, into the gut, and finally to an unexpected place for this trigger: a set of small veins in the liver.
The motion of gulping might provide a quick way for the body to monitor fluid intake. But whatever you swallowed will swiftly arrive in the stomach and gut, and then its identity will become clear to your body as something that can fulfill the body’s need for hydration, or not. Water changes the concentration of nutrients in your blood, and researchers believe that this is the trigger for real satiation.
“There is a mechanism to ensure that what you’re drinking is water, not anything else,” said Yuki Oka, a professor at Caltech and an author of both studies. To find out where the body senses changes to your blood’s concentration, Dr. Oka and his colleagues first ran water into the intestines of mice and watched the behavior of nerves that connect the brain to the gut area, which are believed to work similarly in humans. One major nerve, the vagus nerve, fired the closest in time with the water’s arrival in the intestines, suggesting that this is the route the information takes on the way to the brain.
Then, the researchers went one by one and sliced each of the nerve’s connections to different regions in the gut. To their surprise, nothing changed when they cut off contact to the intestines.
Instead, it was the portal veins of the liver — vessels that carry that blood from around the intestine to the filtering organ — whose isolation silenced the messages back to the brain.
These veins ferry nutrients and fluid into the liver, so it’s plausible that they could be a monitoring center for thirst, Dr. Oka said. The team found that just running water through the portal veins was not enough to get the nerve to fire, however. Something about the water’s arrival had to trigger another part of the body’s hydration Rube Goldberg machine.
The researchers narrowed it down to a hormone called vasoactive intestinal peptide, or VIP. When water reaches the portal veins, VIP levels go up, and it is VIP, rather than the water itself, that causes the vagus to fire, alerting the brain.
As intriguing as that is, the scientists don’t know how the water causes this rise. They are hoping to keep following the signals and identify precisely which cells and molecules connect these unassuming veins and the peptide with the grand acronym.
“That is the major thing that we are in a good position to tackle next,” Dr. Oka said.
And there is probably even more to learn. While VIP causes the vagus nerve to sound off, the signal isn’t as strong as the researchers would expect if it worked alone. Water is so important to the body’s functioning that Dr. Oka and his team think our brains most likely have multiple, redundant ways to monitor it. With every glass of water you drink, you’re putting that system through its paces.