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

Abstract 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 epit...

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Autores principales:	Neeraj Sinha, Maria Suarez-Diez, Evert M. van Schothorst, Jaap Keijer, Vitor A. P. Martins dos Santos, Guido J. E. J. Hooiveld
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c462354ad8b458993d41746fb3efcc9
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spelling	oai:doaj.org-article:9c462354ad8b458993d41746fb3efcc92021-12-02T16:06:12ZPredicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition10.1038/s41598-017-07350-12045-2322https://doaj.org/article/9c462354ad8b458993d41746fb3efcc92017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07350-1https://doaj.org/toc/2045-2322Abstract 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.Neeraj SinhaMaria Suarez-DiezEvert M. van SchothorstJaap KeijerVitor A. P. Martins dos SantosGuido J. E. J. HooiveldNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Neeraj Sinha Maria Suarez-Diez Evert M. van Schothorst Jaap Keijer Vitor A. P. Martins dos Santos Guido J. E. J. Hooiveld Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
description	Abstract 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.
format	article
author	Neeraj Sinha Maria Suarez-Diez Evert M. van Schothorst Jaap Keijer Vitor A. P. Martins dos Santos Guido J. E. J. Hooiveld
author_facet	Neeraj Sinha Maria Suarez-Diez Evert M. van Schothorst Jaap Keijer Vitor A. P. Martins dos Santos Guido J. E. J. Hooiveld
author_sort	Neeraj Sinha
title	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_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_sort	predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9c462354ad8b458993d41746fb3efcc9
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Predicting the murine enterocyte metabolic response to diets that differ in lipid and carbohydrate composition

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