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A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes

Low-carbohydrate ketogenic diets (LCKDs) are used for treating obesity and epilepsy; however, the molecular mechanism of LCKDs in tissues has not been fully investigated. In this study, novel LCKD-associated molecular targets were explored using gene expression profiling in the liver of mice fed a L...

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Autor principal: Okuda, Tetsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527835/
https://www.ncbi.nlm.nih.gov/pubmed/31110277
http://dx.doi.org/10.1038/s41598-019-43952-7
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author Okuda, Tetsuya
author_facet Okuda, Tetsuya
author_sort Okuda, Tetsuya
collection PubMed
description Low-carbohydrate ketogenic diets (LCKDs) are used for treating obesity and epilepsy; however, the molecular mechanism of LCKDs in tissues has not been fully investigated. In this study, novel LCKD-associated molecular targets were explored using gene expression profiling in the liver of mice fed a LCKD. The result showed that the LCKD promoted the expression of glycosyltransferase genes involved in ganglioside synthesis and suppressed the expression of Gm2a, the gene encoding GM2 ganglioside activator protein, a lysosomal protein indispensable for ganglioside degradation. These changes were correlated with increased ganglioside content in the liver and serum. As gangliosides are mainly expressed in central nervous tissues, we also analyzed LCKD effect on cerebral cortex. Although ganglioside levels were unchanged in mice on the LCKD, Gm2a expression was significantly down-regulated. Further analyses suggested that the LCKD altered the expression levels of gangliosides in a limited area of central nervous system tissues susceptible to Gm2a.
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spelling pubmed-65278352019-05-30 A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes Okuda, Tetsuya Sci Rep Article Low-carbohydrate ketogenic diets (LCKDs) are used for treating obesity and epilepsy; however, the molecular mechanism of LCKDs in tissues has not been fully investigated. In this study, novel LCKD-associated molecular targets were explored using gene expression profiling in the liver of mice fed a LCKD. The result showed that the LCKD promoted the expression of glycosyltransferase genes involved in ganglioside synthesis and suppressed the expression of Gm2a, the gene encoding GM2 ganglioside activator protein, a lysosomal protein indispensable for ganglioside degradation. These changes were correlated with increased ganglioside content in the liver and serum. As gangliosides are mainly expressed in central nervous tissues, we also analyzed LCKD effect on cerebral cortex. Although ganglioside levels were unchanged in mice on the LCKD, Gm2a expression was significantly down-regulated. Further analyses suggested that the LCKD altered the expression levels of gangliosides in a limited area of central nervous system tissues susceptible to Gm2a. Nature Publishing Group UK 2019-05-20 /pmc/articles/PMC6527835/ /pubmed/31110277 http://dx.doi.org/10.1038/s41598-019-43952-7 Text en © The Author(s) 2019 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
Okuda, Tetsuya
A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
title A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
title_full A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
title_fullStr A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
title_full_unstemmed A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
title_short A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
title_sort low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527835/
https://www.ncbi.nlm.nih.gov/pubmed/31110277
http://dx.doi.org/10.1038/s41598-019-43952-7
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