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The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue

Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in...

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Detalles Bibliográficos
Autores principales: Sun, Shengyi, Xia, Sheng, Ji, Yewei, Kersten, Sander, Qi, Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357307/
https://www.ncbi.nlm.nih.gov/pubmed/22415881
http://dx.doi.org/10.2337/db11-1389
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author Sun, Shengyi
Xia, Sheng
Ji, Yewei
Kersten, Sander
Qi, Ling
author_facet Sun, Shengyi
Xia, Sheng
Ji, Yewei
Kersten, Sander
Qi, Ling
author_sort Sun, Shengyi
collection PubMed
description Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X(7)), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% high-fat diet (HFD), coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X(7) in adipose tissue. Unexpectedly, P2X(7)-deficient animals on HFD exhibit no changes in metabolic phenotypes, inflammatory responses, or inflammasome activation when compared with the wild-type controls. Similar observations have been obtained in hematopoietic cell–specific P2X(7)-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia but, unexpectedly, is not mediated by the ATP-P2X(7) signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized.
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spelling pubmed-33573072013-06-01 The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue Sun, Shengyi Xia, Sheng Ji, Yewei Kersten, Sander Qi, Ling Diabetes Obesity Studies Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X(7)), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% high-fat diet (HFD), coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X(7) in adipose tissue. Unexpectedly, P2X(7)-deficient animals on HFD exhibit no changes in metabolic phenotypes, inflammatory responses, or inflammasome activation when compared with the wild-type controls. Similar observations have been obtained in hematopoietic cell–specific P2X(7)-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia but, unexpectedly, is not mediated by the ATP-P2X(7) signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized. American Diabetes Association 2012-06 2012-05-14 /pmc/articles/PMC3357307/ /pubmed/22415881 http://dx.doi.org/10.2337/db11-1389 Text en © 2012 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 Obesity Studies
Sun, Shengyi
Xia, Sheng
Ji, Yewei
Kersten, Sander
Qi, Ling
The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue
title The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue
title_full The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue
title_fullStr The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue
title_full_unstemmed The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue
title_short The ATP-P2X(7) Signaling Axis Is Dispensable for Obesity-Associated Inflammasome Activation in Adipose Tissue
title_sort atp-p2x(7) signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue
topic Obesity Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3357307/
https://www.ncbi.nlm.nih.gov/pubmed/22415881
http://dx.doi.org/10.2337/db11-1389
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