Regulation of food intake by mechanosensory ion channels in enteric neurons.

William H Olds,Tian Xu

doi:10.7554/elife.04402

Abstract

Regulation of food intake is fundamental to energy homeostasis in animals. The contribution of non-nutritive and metabolic signals in regulating feeding is unclear. Here we show that enteric neurons play a major role in regulating feeding through specialized mechanosensory ion channels in Drosophila. Modulating activities of a specific subset of enteric neurons, the posterior enteric neurons (PENs), results in sixfold changes in food intake. Deficiency of the mechanosensory ion channel PPK1 gene or RNAi knockdown of its expression in the PENS result in a similar increase in food intake, which can be rescued by expression of wild-type PPK1 in the same neurons. Finally, pharmacological inhibition of the mechanosensory ion channel phenocopies the result of genetic interrogation. Together, our study provides the first molecular genetic evidence that mechanosensory ion channels in the enteric neurons are involved in regulating feeding, offering an enticing alternative to current therapeutic strategy for weight control.

Highlights

The sensation of fullness has been documented as far back as Homer's Odyssey
Recent studies in Drosophila have identified neuronal regulation of food intake and nutrient sensing in the central nervous system (Marella et al, 2012; Dus et al, 2013)
We utilized four previously characterized Gal4 lines that are expressed in enteric neurons in the different parts of the Drosophila digestive system (Figure 1A,B)

Summary

Introduction

The sensation of fullness has been documented as far back as Homer's Odyssey. On the basis of experiments in fruit flies, Olds and Xu suggest an alternative strategy, namely targeting the ‘stretch-sensitive’ ion channels in the neurons in the digestive system that signal to the brain that the body has ingested enough food. Deleting the gene that encodes the PPK1 ion channel had the same effect as silencing neurons, suggesting that drugs that act directly on PPK1 could help to regulate food intake.

Results

Conclusion