We feel full because stretched intestine tells us so

Your gut houses a distinct brain -- extensive web of nerve endings lining your intestine -- which tells you when to stop eating and feel sated, researchers have found.

The nerve endings lining your gut plays an important role in controlling how much you eat by monitoring the contents of the stomach and intestine and then sending signals back to the brain that boost or lower your appetite.

Most scientists believe this feedback involves hormone-sensitive nerve endings in the gut that track the nutrients you consume and calculate when you've had enough, but no one has yet tracked down the exact type of neurons that convey these signals to the brain.

"Given how central eating is to our lives, it is remarkable that we still don't understand how our bodies know to stop being hungry when we eat food," said neuroscientist Zachary Knight, a Howard Hughes Medical Institute Investigator and associate professor in the Department of Physiology at University of California San Francisco.

One of the challenges to answering this question is that the thousands of sensory nerves involved in collecting sensory information from the stomach and intestine come in many different types, yet all of them transmit messages back to the brain via the same giant bundle, which is called the vagus nerve.

Scientists can either block or stimulate the activity of this nerve bundle and change animals' appetites, but how to figure out which vagal nerve endings in particular were responsible for the change?

To resolve this mystery, the team, led by postdoctoral researcher Ling Bai, comprehensively mapped the molecular and anatomical identities of the vagal sensory cell types neurons innervating the stomach and intestine.

This new map, published in the journal Cell, allowed the researchers to selectively stimulate different types of vagal neurons in mice, revealing that intestinal stretch sensors are uniquely able to stop even hungry mice from wanting to eat.

"The vagus nerve is the major neural pathway that transmits information from gut to brain, but the identities and functions of the specific neurons that are sending these signals were still poorly understood," Bai said.

Using these techniques, Bai and colleagues discovered that mucosal endings actually come in many different varieties -- four of which the researchers studied in detail.

Some of these were mainly found in the stomach and others mainly in different parts of the intestines, with each type specialized to sense a particular combination of nutrient-related hormones.

The findings also suggest a potential explanation for why bariatric surgery -- performed to treat extreme obesity by reducing the size of the gut -- is so mysteriously effective at promoting long-term appetite and weight reduction.