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A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling
AIMS: Obesity and hyperlipidaemia are associated with insulin resistance (IR); however, the mechanisms responsible remain incompletely understood. Pro-atherogenic hyperlipidaemic states are characterized by inflammation, oxidant stress, and pathophysiologic oxidized lipids, including ligands for the...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028977/ https://www.ncbi.nlm.nih.gov/pubmed/21088116 http://dx.doi.org/10.1093/cvr/cvq360 |
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author | Kennedy, David J. Kuchibhotla, Sai Westfall, Kristen M. Silverstein, Roy L. Morton, Richard E. Febbraio, Maria |
author_facet | Kennedy, David J. Kuchibhotla, Sai Westfall, Kristen M. Silverstein, Roy L. Morton, Richard E. Febbraio, Maria |
author_sort | Kennedy, David J. |
collection | PubMed |
description | AIMS: Obesity and hyperlipidaemia are associated with insulin resistance (IR); however, the mechanisms responsible remain incompletely understood. Pro-atherogenic hyperlipidaemic states are characterized by inflammation, oxidant stress, and pathophysiologic oxidized lipids, including ligands for the scavenger receptor CD36. Here we tested the hypothesis that the absence of CD36 protects mice from IR associated with diet-induced obesity and hyperlipidaemia. METHODS AND RESULTS: Adipose tissue from CD36(−/−) mice demonstrated a less inflammatory phenotype and improved insulin signalling in vivo and at the level of the adipocyte and macrophage. The pathophysiologic ligand oxidized low-density lipoprotein (oxLDL) activated c-Jun N-terminal kinase (JNK) and disrupted insulin signalling in both adipocytes and macrophages in a CD36-dependent manner. Macrophages isolated from CD36(−/−) mice after high-fat diet feeding elicited less JNK activation and inhibition of insulin signalling in adipocytes after co-culture compared with wild-type macrophages. CONCLUSION: These data suggest that a CD36-dependent inflammatory paracrine loop between adipocytes and macrophages facilitates chronic inflammation and contributes to IR common in obesity and dyslipidaemia. |
format | Text |
id | pubmed-3028977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-30289772011-01-27 A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling Kennedy, David J. Kuchibhotla, Sai Westfall, Kristen M. Silverstein, Roy L. Morton, Richard E. Febbraio, Maria Cardiovasc Res Original Articles AIMS: Obesity and hyperlipidaemia are associated with insulin resistance (IR); however, the mechanisms responsible remain incompletely understood. Pro-atherogenic hyperlipidaemic states are characterized by inflammation, oxidant stress, and pathophysiologic oxidized lipids, including ligands for the scavenger receptor CD36. Here we tested the hypothesis that the absence of CD36 protects mice from IR associated with diet-induced obesity and hyperlipidaemia. METHODS AND RESULTS: Adipose tissue from CD36(−/−) mice demonstrated a less inflammatory phenotype and improved insulin signalling in vivo and at the level of the adipocyte and macrophage. The pathophysiologic ligand oxidized low-density lipoprotein (oxLDL) activated c-Jun N-terminal kinase (JNK) and disrupted insulin signalling in both adipocytes and macrophages in a CD36-dependent manner. Macrophages isolated from CD36(−/−) mice after high-fat diet feeding elicited less JNK activation and inhibition of insulin signalling in adipocytes after co-culture compared with wild-type macrophages. CONCLUSION: These data suggest that a CD36-dependent inflammatory paracrine loop between adipocytes and macrophages facilitates chronic inflammation and contributes to IR common in obesity and dyslipidaemia. Oxford University Press 2011-02-15 2010-11-18 /pmc/articles/PMC3028977/ /pubmed/21088116 http://dx.doi.org/10.1093/cvr/cvq360 Text en Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2010. For permissions please email: journals.permissions@oup.com. http://creativecommons.org/licenses/by-nc/2.5/ The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oup.com. |
spellingShingle | Original Articles Kennedy, David J. Kuchibhotla, Sai Westfall, Kristen M. Silverstein, Roy L. Morton, Richard E. Febbraio, Maria A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling |
title | A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling |
title_full | A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling |
title_fullStr | A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling |
title_full_unstemmed | A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling |
title_short | A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling |
title_sort | cd36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028977/ https://www.ncbi.nlm.nih.gov/pubmed/21088116 http://dx.doi.org/10.1093/cvr/cvq360 |
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