title: Regulation of food intake by mechanosensory ion channels in enteric neurons.
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.
authors.affiliation: Department of Genetics, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, United States.
authors.forename: William H
authors.initials: WH
authors.lastname: Olds
authors.affiliation: Department of Genetics, Howard Hughes Medical Institute, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, United States.
authors.forename: Tian
authors.initials: T
authors.lastname: Xu
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D004435:Eating; D017615:Enteric Nervous System / Q000166:cytology*; D005247:Feeding Behavior; D040542:Mechanotransduction, Cellular; D009474:Neurons / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D015222:Sodium Channels; C532965:ppk protein, Drosophila
keywords: D. melanogaster; enteric neurons; feeding; gut; human biology; medicine; neuroscience