Fat pill possible, at a stretch

How the intestines register fullness and tell the brain to stop eating has been uncovered by researchers in the US.

While it's well known that physical stretch and distention of the stomach and intestines forms part of a feedback loop used by the nervous system to signal feeling full, the detection system and nerve wiring responsible weren't known.

Now, working with flies, Yale scientists Williams Olds and Tian Xu have discovered a family of stretch-sensitive nerve cells that wrap themselves around the intestines, become more active as the intestines distend with food, and connect to the brain where to shut off eating.

Fruit flies were the ideal study subjects for the study because scientists have previously developed a molecular toolbox that makes is possible to deactivate specific genes in discrete target tissues.

Olds and Xu used this approach to both change the electrical activity of nerve cells supplying the fly intestines and then measuring how this affected the level of glucose in the fly's blood and the level of food intake.

One class of nerve cells, when deactivated in this way, triggered the flies to increase feeding sixfold. Enhancing the activity of these cells on the other hand, mimicking a full stomach, led to a drop in food intake and a corresponding fall in blood glucose.

Examining these nerve cells in more detail, the Yale researchers, who have published the work in the journal eLife, found that they express a stretch-sensor gene called PPK1, which is also used elsewhere in the body to detect movements and mechanical deformation of tissues. Knocking out this PPK1 gene also produced flies prone to over-eating.

"Previously we knew that the intestines were sensitive to stretch and feeling full," says Olds, "but we were clueless as to the identity of the system that detects this."

Intriguingly, humans also have the same nerve cells and the equivalent gene to the flies, indicating that the same process that keeps the fly appetite in check is also acting inside us, prompting speculation that this mechanism might have anti-fat-pill potential.

"The stretch-sensitive nerves are in the intestines where a drug would be absorbed," says Olds. "So it would be relatively easy to target them pharmacologically, switch them on and fool the gut into thinking it's more full than it is, cutting down eating..."