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Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression

OBJECTIVE: Resistin is a secreted polypeptide that impairs glucose metabolism and, in rodents, is derived exclusively from adipocytes. In murine obesity, resistin circulates at elevated levels but its gene expression in adipose tissue is paradoxically reduced. The mechanism behind the downregulation...

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Autores principales: Lefterova, Martina I., Mullican, Shannon E., Tomaru, Takuya, Qatanani, Mohammed, Schupp, Michael, Lazar, Mitchell A.
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712799/
https://www.ncbi.nlm.nih.gov/pubmed/19491212
http://dx.doi.org/10.2337/db08-1706
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author Lefterova, Martina I.
Mullican, Shannon E.
Tomaru, Takuya
Qatanani, Mohammed
Schupp, Michael
Lazar, Mitchell A.
author_facet Lefterova, Martina I.
Mullican, Shannon E.
Tomaru, Takuya
Qatanani, Mohammed
Schupp, Michael
Lazar, Mitchell A.
author_sort Lefterova, Martina I.
collection PubMed
description OBJECTIVE: Resistin is a secreted polypeptide that impairs glucose metabolism and, in rodents, is derived exclusively from adipocytes. In murine obesity, resistin circulates at elevated levels but its gene expression in adipose tissue is paradoxically reduced. The mechanism behind the downregulation of resistin mRNA is poorly understood. We investigated whether endoplasmic reticulum (ER) stress, which is characteristic of obese adipose tissue, regulates resistin expression in cultured mouse adipocytes. RESEARCH DESIGN AND METHODS: The effects of endoplasmic stress inducers on resistin mRNA and secreted protein levels were examined in differentiated 3T3-L1 adipocytes, focusing on the expression and genomic binding of transcriptional regulators of resistin. The association between downregulated resistin mRNA and induction of ER stress was also investigated in the adipose tissue of mice fed a high-fat diet. RESULTS: ER stress reduced resistin mRNA in 3T3-L1 adipocytes in a time- and dose-dependent manner. The effects of ER stress were transcriptional because of downregulation of CAAT/enhancer binding protein-α and peroxisome proliferator–activated receptor-γ transcriptional activators and upregulation of the transcriptional repressor CAAT/enhancer binding protein homologous protein-10 (CHOP10). Resistin protein was also substantially downregulated, showing a close correspondence with mRNA levels in 3T3-L1 adipocytes as well as in the fat pads of obese mice. CONCLUSIONS: ER stress is a potent regulator of resistin, suggesting that ER stress may underlie the local downregulation of resistin mRNA and protein in fat in murine obesity. The paradoxical increase in plasma may be because of various systemic abnormalities associated with obesity and insulin resistance.
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spelling pubmed-27127992010-08-01 Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression Lefterova, Martina I. Mullican, Shannon E. Tomaru, Takuya Qatanani, Mohammed Schupp, Michael Lazar, Mitchell A. Diabetes Original Article OBJECTIVE: Resistin is a secreted polypeptide that impairs glucose metabolism and, in rodents, is derived exclusively from adipocytes. In murine obesity, resistin circulates at elevated levels but its gene expression in adipose tissue is paradoxically reduced. The mechanism behind the downregulation of resistin mRNA is poorly understood. We investigated whether endoplasmic reticulum (ER) stress, which is characteristic of obese adipose tissue, regulates resistin expression in cultured mouse adipocytes. RESEARCH DESIGN AND METHODS: The effects of endoplasmic stress inducers on resistin mRNA and secreted protein levels were examined in differentiated 3T3-L1 adipocytes, focusing on the expression and genomic binding of transcriptional regulators of resistin. The association between downregulated resistin mRNA and induction of ER stress was also investigated in the adipose tissue of mice fed a high-fat diet. RESULTS: ER stress reduced resistin mRNA in 3T3-L1 adipocytes in a time- and dose-dependent manner. The effects of ER stress were transcriptional because of downregulation of CAAT/enhancer binding protein-α and peroxisome proliferator–activated receptor-γ transcriptional activators and upregulation of the transcriptional repressor CAAT/enhancer binding protein homologous protein-10 (CHOP10). Resistin protein was also substantially downregulated, showing a close correspondence with mRNA levels in 3T3-L1 adipocytes as well as in the fat pads of obese mice. CONCLUSIONS: ER stress is a potent regulator of resistin, suggesting that ER stress may underlie the local downregulation of resistin mRNA and protein in fat in murine obesity. The paradoxical increase in plasma may be because of various systemic abnormalities associated with obesity and insulin resistance. American Diabetes Association 2009-08 2009-06-02 /pmc/articles/PMC2712799/ /pubmed/19491212 http://dx.doi.org/10.2337/db08-1706 Text en © 2009 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Lefterova, Martina I.
Mullican, Shannon E.
Tomaru, Takuya
Qatanani, Mohammed
Schupp, Michael
Lazar, Mitchell A.
Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression
title Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression
title_full Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression
title_fullStr Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression
title_full_unstemmed Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression
title_short Endoplasmic Reticulum Stress Regulates Adipocyte Resistin Expression
title_sort endoplasmic reticulum stress regulates adipocyte resistin expression
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712799/
https://www.ncbi.nlm.nih.gov/pubmed/19491212
http://dx.doi.org/10.2337/db08-1706
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