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The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents

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Title: The homeostatic dynamics of feeding behaviour identify novel mechanisms of anorectic agents
Authors: McGrath, T
Spreckley, E
Rodriguez, A
Viscomi, C
Alamshah, A
Akalestou, E
Murphy, K
Jones, N
Item Type: Journal Article
Abstract: Better understanding of feeding behaviour will be vital in reducing obesity and metabolic syndrome, but we lack a standard model that captures the complexity of feeding behaviour. We construct an accurate stochastic model of rodent feeding at the bout level in order to perform quantitative behavioural analysis. Analysing the different effects on feeding behaviour of PYY3-36, lithium chloride, GLP-1 and leptin shows the precise behavioural changes caused by each anorectic agent. Our analysis demonstrates that the changes in feeding behaviour evoked by the anorectic agents investigated do not mimic the behaviour of well-fed animals, and that the intermeal interval is influenced by fullness. We show how robust homeostatic control of feeding thwarts attempts to reduce food intake, and how this might be overcome. In silico experiments suggest that introducing a minimum intermeal interval or modulating upper gut emptying can be as effective as anorectic drug administration.
Issue Date: 5-Dec-2019
Date of Acceptance: 1-Nov-2019
URI: http://hdl.handle.net/10044/1/74858
DOI: 10.1371/journal.pbio.3000482
ISSN: 1544-9173
Publisher: Public Library of Science (PLoS)
Start Page: 1
End Page: 30
Journal / Book Title: PLoS Biology
Volume: 17
Issue: 12
Copyright Statement: © 2019 McGrath et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
BBSRC DTP
NC3Rs (National Centre for the Replacement, Refinement and Reduction of Animals in Research)
Biotechnology and Biological Sciences Research Council (BBSRC)
Funder's Grant Number: EP/N014529/1
BB/J014575/1
NC/K500379/1
BB/I001816/1
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biology
Life Sciences & Biomedicine - Other Topics
DETERMINISTIC MARKOV-PROCESSES
NEURONS MEDIATE
POMC NEURONS
BODY-WEIGHT
MEAL
MODEL
SATIATION
SATIETY
OBESITY
LEPTIN
Animals
Appetite Depressants
Eating
Feeding Behavior
Glucagon-Like Peptide 1
Homeostasis
Leptin
Male
Mice
Obesity
Peptide Fragments
Peptide YY
Rats
Animals
Mice
Rats
Obesity
Peptide YY
Leptin
Peptide Fragments
Appetite Depressants
Feeding Behavior
Homeostasis
Eating
Male
Glucagon-Like Peptide 1
06 Biological Sciences
07 Agricultural and Veterinary Sciences
11 Medical and Health Sciences
Developmental Biology
Publication Status: Published
Article Number: ARTN e3000482
Online Publication Date: 2019-12-05
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Mathematics
Applied Mathematics and Mathematical Physics
Faculty of Medicine
Faculty of Natural Sciences