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Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells

Small intestinal epithelial cells (sIECs) have a significant share in whole body metabolism as they perform enzymatic digestion and absorption of nutrients. Furthermore, the diet plays a key role in a number of complex diseases including obesity and diabetes. The impact of diet and altered genetic b...

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Autores principales: Sahoo, Swagatika, Thiele, Ines
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674809/
https://www.ncbi.nlm.nih.gov/pubmed/23492669
http://dx.doi.org/10.1093/hmg/ddt119
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author Sahoo, Swagatika
Thiele, Ines
author_facet Sahoo, Swagatika
Thiele, Ines
author_sort Sahoo, Swagatika
collection PubMed
description Small intestinal epithelial cells (sIECs) have a significant share in whole body metabolism as they perform enzymatic digestion and absorption of nutrients. Furthermore, the diet plays a key role in a number of complex diseases including obesity and diabetes. The impact of diet and altered genetic backgrounds on human metabolism may be studied by using computational modeling. A metabolic reconstruction of human sIECs was manually assembled using the literature. The resulting sIEC model was subjected to two different diets to obtain condition-specific metabolic models. Fifty defined metabolic tasks evaluated the functionalities of these models, along with the respective secretion profiles, which distinguished between impacts of different dietary regimes. Under the average American diet, the sIEC model resulted in higher secretion flux for metabolites implicated in metabolic syndrome. In addition, enzymopathies were analyzed in the context of the sIEC metabolism. Computed results were compared with reported gastrointestinal (GI) pathologies and biochemical defects as well as with biomarker patterns used in their diagnosis. Based on our simulations, we propose that (i) sIEC metabolism is perturbed by numerous enzymopathies, which can be used to study cellular adaptive mechanisms specific for such disorders, and in the identification of novel co-morbidities, (ii) porphyrias are associated with both heme synthesis and degradation and (iii) disturbed intestinal gamma-aminobutyric acid synthesis may be linked to neurological manifestations of various enzymopathies. Taken together, the sIEC model represents a comprehensive, biochemically accurate platform for studying the function of sIEC and their role in whole body metabolism.
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spelling pubmed-36748092013-06-06 Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells Sahoo, Swagatika Thiele, Ines Hum Mol Genet Articles Small intestinal epithelial cells (sIECs) have a significant share in whole body metabolism as they perform enzymatic digestion and absorption of nutrients. Furthermore, the diet plays a key role in a number of complex diseases including obesity and diabetes. The impact of diet and altered genetic backgrounds on human metabolism may be studied by using computational modeling. A metabolic reconstruction of human sIECs was manually assembled using the literature. The resulting sIEC model was subjected to two different diets to obtain condition-specific metabolic models. Fifty defined metabolic tasks evaluated the functionalities of these models, along with the respective secretion profiles, which distinguished between impacts of different dietary regimes. Under the average American diet, the sIEC model resulted in higher secretion flux for metabolites implicated in metabolic syndrome. In addition, enzymopathies were analyzed in the context of the sIEC metabolism. Computed results were compared with reported gastrointestinal (GI) pathologies and biochemical defects as well as with biomarker patterns used in their diagnosis. Based on our simulations, we propose that (i) sIEC metabolism is perturbed by numerous enzymopathies, which can be used to study cellular adaptive mechanisms specific for such disorders, and in the identification of novel co-morbidities, (ii) porphyrias are associated with both heme synthesis and degradation and (iii) disturbed intestinal gamma-aminobutyric acid synthesis may be linked to neurological manifestations of various enzymopathies. Taken together, the sIEC model represents a comprehensive, biochemically accurate platform for studying the function of sIEC and their role in whole body metabolism. Oxford University Press 2013-07-01 2013-03-13 /pmc/articles/PMC3674809/ /pubmed/23492669 http://dx.doi.org/10.1093/hmg/ddt119 Text en © The Author 2013. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/3.0/), which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permission@oup.com
spellingShingle Articles
Sahoo, Swagatika
Thiele, Ines
Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
title Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
title_full Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
title_fullStr Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
title_full_unstemmed Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
title_short Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
title_sort predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674809/
https://www.ncbi.nlm.nih.gov/pubmed/23492669
http://dx.doi.org/10.1093/hmg/ddt119
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