Dissertation/Thesis Abstract

Regulation of Food Intake by Mechanosensory Ion Channels in Enteric Neurons
by Olds, William Henry, III, Ph.D., Yale University, 2015, 73; 3663652
Abstract (Summary)

Balancing energy expenditure and uptake is critical for animals' survival. If expenditure greatly exceeds energy uptake, animals can starve and die of malnutrition. If uptake exceeds expenditure, animals can become obese and develop a host of health issues. The mechanisms behind this energy balance are an active area of research. In Drosophila, the neurons regulating satiety have begun to emerge1-6. Several of these neurons activate in response to starvation, but they are not sensitive to nutrients3,4,6 These data raise the possibility that non-metabolic and non-nutritive signals such as gastric mechanic tension are critical to controlling food intake levels. In this dissertation, I show that posterior enteric neurons (PENs) require mechanosensory ion channels to control food intake. Activating the PENs halves food intake, while inactivating them triples the amount compared to controls. Genetic and pharmacological interrogations reveal that mechanosensory PPK1 is integral to the regulation of feeding by these neurons. These results suggest that the PENs, via PPK1, activate in response to gastric mechanic tension and transmit that information to the satiety center in the brain. Preliminary evidence using neuronal epistasis suggests that the cupcake neurons4 may be a downstream target of the PENs. Overall, my study demonstrates the importance of enteric neuronal signaling in energy homeostasis. These results may provide insight into how mammals sense gastric mechanic tension and suggest potential drug targets for obesity treatment.

Indexing (document details)
Advisor: Xu, Tian
School: Yale University
School Location: United States -- Connecticut
Source: DAI-B 76/11(E), Dissertation Abstracts International
Subjects: Neurosciences
Keywords: Enteric Neurons, Food Intake
Publication Number: 3663652
ISBN: 978-1-321-95765-5
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