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Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition

The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial ce...

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Autores principales: Sinha, Neeraj, Suarez-Diez, Maria, van Schothorst, Evert M., Keijer, Jaap, Martins dos Santos, Vitor A. P., Hooiveld, Guido J. E. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562867/
https://www.ncbi.nlm.nih.gov/pubmed/28821741
http://dx.doi.org/10.1038/s41598-017-07350-1
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author Sinha, Neeraj
Suarez-Diez, Maria
van Schothorst, Evert M.
Keijer, Jaap
Martins dos Santos, Vitor A. P.
Hooiveld, Guido J. E. J.
author_facet Sinha, Neeraj
Suarez-Diez, Maria
van Schothorst, Evert M.
Keijer, Jaap
Martins dos Santos, Vitor A. P.
Hooiveld, Guido J. E. J.
author_sort Sinha, Neeraj
collection PubMed
description The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu_ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids. Our simulation results predicted luminal sodium as a limiting factor for active glucose absorption; necessity of apical localization of glucose transporter GLUT2 for absorption of all glucose in the postprandial state; potential for gluconeogenesis in enterocytes; and the requirement of oxygen for the formation of endogenous cholesterol needed for chylomicron formation under luminal cholesterol-free conditions. In addition, for a number of enzymopathies related to intestinal carbohydrate and lipid metabolism it was found that their effects might be ameliorated through dietary interventions. In conclusion, our improved enterocyte-specific model was shown to be a suitable platform to study effects of dietary interventions on enterocyte metabolism, and provided novel and deeper insights into enterocyte metabolism.
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spelling pubmed-55628672017-08-21 Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition Sinha, Neeraj Suarez-Diez, Maria van Schothorst, Evert M. Keijer, Jaap Martins dos Santos, Vitor A. P. Hooiveld, Guido J. E. J. Sci Rep Article The small intestine serves as gatekeeper at the interface between body and diet and is thought to play an important role in the etiology of obesity and associated metabolic disorders. A computational modelling approach was used to improve our understanding of the metabolic responses of epithelial cells to different diets. A constraint based, mouse-specific enterocyte metabolic model (named mmu_ENT717) was constructed to describe the impact of four fully characterized semi-purified diets, that differed in lipid and carbohydrate composition, on uptake, metabolism, as well as secretion of carbohydrates and lipids. Our simulation results predicted luminal sodium as a limiting factor for active glucose absorption; necessity of apical localization of glucose transporter GLUT2 for absorption of all glucose in the postprandial state; potential for gluconeogenesis in enterocytes; and the requirement of oxygen for the formation of endogenous cholesterol needed for chylomicron formation under luminal cholesterol-free conditions. In addition, for a number of enzymopathies related to intestinal carbohydrate and lipid metabolism it was found that their effects might be ameliorated through dietary interventions. In conclusion, our improved enterocyte-specific model was shown to be a suitable platform to study effects of dietary interventions on enterocyte metabolism, and provided novel and deeper insights into enterocyte metabolism. Nature Publishing Group UK 2017-08-18 /pmc/articles/PMC5562867/ /pubmed/28821741 http://dx.doi.org/10.1038/s41598-017-07350-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sinha, Neeraj
Suarez-Diez, Maria
van Schothorst, Evert M.
Keijer, Jaap
Martins dos Santos, Vitor A. P.
Hooiveld, Guido J. E. J.
Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
title Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
title_full Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
title_fullStr Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
title_full_unstemmed Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
title_short Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
title_sort predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562867/
https://www.ncbi.nlm.nih.gov/pubmed/28821741
http://dx.doi.org/10.1038/s41598-017-07350-1
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