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HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders
A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based o...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570097/ https://www.ncbi.nlm.nih.gov/pubmed/23319699 http://dx.doi.org/10.1084/jem.20121357 |
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author | Gautier, Emmanuel L. Westerterp, Marit Bhagwat, Neha Cremers, Serge Shih, Alan Abdel-Wahab, Omar Lütjohann, Dieter Randolph, Gwendalyn J. Levine, Ross L. Tall, Alan R. Yvan-Charvet, Laurent |
author_facet | Gautier, Emmanuel L. Westerterp, Marit Bhagwat, Neha Cremers, Serge Shih, Alan Abdel-Wahab, Omar Lütjohann, Dieter Randolph, Gwendalyn J. Levine, Ross L. Tall, Alan R. Yvan-Charvet, Laurent |
author_sort | Gautier, Emmanuel L. |
collection | PubMed |
description | A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based on expression of human leukemia disease alleles, we uncovered a mechanism by which proliferating and inflammatory myeloid cells take up and oxidize glucose during the feeding period, contributing to energy dissipation and subsequent loss of adipose mass. In vivo, lentiviral inhibition of Glut1 by shRNA prevented myeloproliferation and adipose tissue loss in mice with defective cholesterol efflux pathway in leukocytes. Thus, Glut1 was necessary to sustain proliferation and potentially divert glucose from fat storage. We also showed that overexpression of the human ApoA-I transgene to raise high-density lipoprotein (HDL) levels decreased Glut1 expression, dampened myeloproliferation, and prevented fat loss. These experiments suggest that inhibition of Glut-1 and HDL cholesterol–raising therapies could provide novel therapeutic approaches to treat the energy imbalance observed in myeloproliferative disorders. |
format | Online Article Text |
id | pubmed-3570097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-35700972013-08-11 HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders Gautier, Emmanuel L. Westerterp, Marit Bhagwat, Neha Cremers, Serge Shih, Alan Abdel-Wahab, Omar Lütjohann, Dieter Randolph, Gwendalyn J. Levine, Ross L. Tall, Alan R. Yvan-Charvet, Laurent J Exp Med Article A high metabolic rate in myeloproliferative disorders is a common complication of neoplasms, but the underlying mechanisms are incompletely understood. Using three different mouse models of myeloproliferative disorders, including mice with defective cholesterol efflux pathways and two models based on expression of human leukemia disease alleles, we uncovered a mechanism by which proliferating and inflammatory myeloid cells take up and oxidize glucose during the feeding period, contributing to energy dissipation and subsequent loss of adipose mass. In vivo, lentiviral inhibition of Glut1 by shRNA prevented myeloproliferation and adipose tissue loss in mice with defective cholesterol efflux pathway in leukocytes. Thus, Glut1 was necessary to sustain proliferation and potentially divert glucose from fat storage. We also showed that overexpression of the human ApoA-I transgene to raise high-density lipoprotein (HDL) levels decreased Glut1 expression, dampened myeloproliferation, and prevented fat loss. These experiments suggest that inhibition of Glut-1 and HDL cholesterol–raising therapies could provide novel therapeutic approaches to treat the energy imbalance observed in myeloproliferative disorders. The Rockefeller University Press 2013-02-11 /pmc/articles/PMC3570097/ /pubmed/23319699 http://dx.doi.org/10.1084/jem.20121357 Text en © 2013 Gautier et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Gautier, Emmanuel L. Westerterp, Marit Bhagwat, Neha Cremers, Serge Shih, Alan Abdel-Wahab, Omar Lütjohann, Dieter Randolph, Gwendalyn J. Levine, Ross L. Tall, Alan R. Yvan-Charvet, Laurent HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders |
title | HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders |
title_full | HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders |
title_fullStr | HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders |
title_full_unstemmed | HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders |
title_short | HDL and Glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders |
title_sort | hdl and glut1 inhibition reverse a hypermetabolic state in mouse models of myeloproliferative disorders |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570097/ https://www.ncbi.nlm.nih.gov/pubmed/23319699 http://dx.doi.org/10.1084/jem.20121357 |
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