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Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol
Sterol Response Element Binding Protein 2 (SREBP2) transcription factor is a master regulator of cholesterol homeostasis. Treatment with statins, inhibitors of cholesterol synthesis, activates intestinal SREBP2, which may hinder their cholesterol-lowering effects. Overactivation of SREBP2 in mouse l...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896331/ https://www.ncbi.nlm.nih.gov/pubmed/24465397 http://dx.doi.org/10.1371/journal.pone.0084221 |
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author | Ma, Ke Malhotra, Pooja Soni, Vinay Hedroug, Omar Annaba, Fadi Dudeja, Amish Shen, Le Turner, Jerrold R. Khramtsova, Ekaterina A. Saksena, Seema Dudeja, Pradeep K. Gill, Ravinder K. Alrefai, Waddah A. |
author_facet | Ma, Ke Malhotra, Pooja Soni, Vinay Hedroug, Omar Annaba, Fadi Dudeja, Amish Shen, Le Turner, Jerrold R. Khramtsova, Ekaterina A. Saksena, Seema Dudeja, Pradeep K. Gill, Ravinder K. Alrefai, Waddah A. |
author_sort | Ma, Ke |
collection | PubMed |
description | Sterol Response Element Binding Protein 2 (SREBP2) transcription factor is a master regulator of cholesterol homeostasis. Treatment with statins, inhibitors of cholesterol synthesis, activates intestinal SREBP2, which may hinder their cholesterol-lowering effects. Overactivation of SREBP2 in mouse liver was shown to have no effect on plasma cholesterol. However, the influence of activating intestinal SREBP2 on plasma cholesterol is not known. We have generated a novel transgenic mouse model with intestine specific overexpression of active SREBP2 (ISR2) driven by villin promoter. ISR2 mice showed overexpression of active SREBP2 specifically in the intestine. Microarray analysis of jejunal RNA from ISR2 mice showed a significant increase in genes involved in fatty acid and cholesterol synthesis. Cholesterol and triglyceride (TG) in jejunum and liver (mg/g protein) were significantly increased in ISR2 vs wild type mice. Serum Cholesterol was significantly increased in VLDL and LDL fractions whereas the level of serum triglycerides was decreased in ISR2 vs wild type mice. In conclusion, activation of intestinal SREBP2 alone seems to be sufficient to increase plasma cholesterol, highlighting the essential role of intestine in maintaining cholesterol homeostasis in the body. |
format | Online Article Text |
id | pubmed-3896331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38963312014-01-24 Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol Ma, Ke Malhotra, Pooja Soni, Vinay Hedroug, Omar Annaba, Fadi Dudeja, Amish Shen, Le Turner, Jerrold R. Khramtsova, Ekaterina A. Saksena, Seema Dudeja, Pradeep K. Gill, Ravinder K. Alrefai, Waddah A. PLoS One Research Article Sterol Response Element Binding Protein 2 (SREBP2) transcription factor is a master regulator of cholesterol homeostasis. Treatment with statins, inhibitors of cholesterol synthesis, activates intestinal SREBP2, which may hinder their cholesterol-lowering effects. Overactivation of SREBP2 in mouse liver was shown to have no effect on plasma cholesterol. However, the influence of activating intestinal SREBP2 on plasma cholesterol is not known. We have generated a novel transgenic mouse model with intestine specific overexpression of active SREBP2 (ISR2) driven by villin promoter. ISR2 mice showed overexpression of active SREBP2 specifically in the intestine. Microarray analysis of jejunal RNA from ISR2 mice showed a significant increase in genes involved in fatty acid and cholesterol synthesis. Cholesterol and triglyceride (TG) in jejunum and liver (mg/g protein) were significantly increased in ISR2 vs wild type mice. Serum Cholesterol was significantly increased in VLDL and LDL fractions whereas the level of serum triglycerides was decreased in ISR2 vs wild type mice. In conclusion, activation of intestinal SREBP2 alone seems to be sufficient to increase plasma cholesterol, highlighting the essential role of intestine in maintaining cholesterol homeostasis in the body. Public Library of Science 2014-01-20 /pmc/articles/PMC3896331/ /pubmed/24465397 http://dx.doi.org/10.1371/journal.pone.0084221 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Ma, Ke Malhotra, Pooja Soni, Vinay Hedroug, Omar Annaba, Fadi Dudeja, Amish Shen, Le Turner, Jerrold R. Khramtsova, Ekaterina A. Saksena, Seema Dudeja, Pradeep K. Gill, Ravinder K. Alrefai, Waddah A. Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol |
title | Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol |
title_full | Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol |
title_fullStr | Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol |
title_full_unstemmed | Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol |
title_short | Overactivation of Intestinal SREBP2 in Mice Increases Serum Cholesterol |
title_sort | overactivation of intestinal srebp2 in mice increases serum cholesterol |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896331/ https://www.ncbi.nlm.nih.gov/pubmed/24465397 http://dx.doi.org/10.1371/journal.pone.0084221 |
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