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Taste buds are the first line of defense against eating too much and too fast

When you eagerly dig into a long-awaited dinner, signals from your stomach, not your taste buds, tell your brain keep you from eating so much you’ll regret it — or so it’s been thought. That theory had never really been directly tested until a team of scientists at UC San Francisco recently took up the question.

Taste wins over stomach signals

The picture, it turns out, is a little different. The team, led by Zachary Knight, PhD, a UCSF professor of physiology in the Kavli Institute for Fundamental Neuroscience, discovered that it’s our sense of taste that pulls us back from the brink of food inhalation on a hungry day.

Stimulated by the perception of flavor, a set of neurons in the brain leaps to attention almost immediately to curtail our food intake.

Knight says, “We’ve uncovered a logic the brainstem uses to control how fast and how much we eat, using two different kinds of signals, one coming from the mouth, and one coming much later from the gut.”

Knight is also an investigator with the Howard Hughes Medical Institute and a member of the UCSF Weill Institute for Neurosciences. He further elucidates, “This discovery gives us a new framework to understand how we control our eating.”

The study could help reveal exactly how weight-loss drugs like Ozempic work, and how to make them more effective.

Revisiting Pavlov’s theories about taste

Pavlov proposed over a century ago that the sight, smell and taste of food are important for regulating digestion. More recent studies in the 1970s and 1980s have also suggested that the taste of food may restrain how fast we eat.

However, it’s been impossible to study the relevant brain activity during eating because the brain cells that control this process are located deep in the brainstem. Their location makes them hard to access or record in an animal that’s awake.

New techniques developed by lead author Truong Ly, PhD, a graduate student in Knight’s lab, allowed for the first-ever imaging and recording of a brainstem structure critical for feeling full, called the nucleus of the solitary tract, or NTS, in an awake, active mouse.

Surprising discovery

The team found that when they put food directly into the mouse’s stomach, brain cells called PRLH (for prolactin-releasing hormone) were activated by nutrient signals sent from the GI tract.

However, when they allowed the mice to eat the food as they normally would, those signals from the gut didn’t show up. Instead, the PRLH brain cells switched to a new activity pattern that was entirely controlled by signals from the mouth.

“It was a total surprise that these cells were activated by the perception of taste,” said Ly. “It shows that there are other components of the appetite-control system that we should be thinking about.”

Balancing act between taste and stomach

While it may seem counterintuitive for our brains to slow eating when we’re hungry, the brain is actually using the taste of food in two different ways at the same time.

One part is saying, “This tastes good, eat more,” and another part is watching how fast you’re eating and saying, “Slow down or you’re going to be sick.”

Meanwhile, it takes many minutes for a different group of brain cells, called CGC neurons, to begin responding to signals from the stomach and intestines. These drugs act on the same region of the brainstem that Ly’s technology has finally allowed researchers to study.

A deeper understanding of how signals from different parts of the body control appetite would open doors to designing weight-loss regimens designed for the individual ways people eat by optimizing how the signals from the two sets of brain cells interact, the researchers said.

The team plans to investigate those interactions, seeking to better understand how taste signals from food interact with feedback from the gut to suppress our appetite during a meal.

The full study was published in the journal Nature.

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