Macrophage and adipocyte interaction as a source of inflammation in kidney disease

Abstract In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the cont...

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Autores principales: Cristina Martos-Rus, Goni Katz-Greenberg, Zhao Lin, Eurico Serrano, Diana Whitaker-Menezes, Marina Domingo-Vidal, Megan Roche, Kavitha Ramaswamy, Douglas C. Hooper, Bonita Falkner, Maria P. Martinez Cantarin
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/bc495e9753f94b0790517583f240a4d3
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spelling oai:doaj.org-article:bc495e9753f94b0790517583f240a4d32021-12-02T14:06:49ZMacrophage and adipocyte interaction as a source of inflammation in kidney disease10.1038/s41598-021-82685-42045-2322https://doaj.org/article/bc495e9753f94b0790517583f240a4d32021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82685-4https://doaj.org/toc/2045-2322Abstract In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.Cristina Martos-RusGoni Katz-GreenbergZhao LinEurico SerranoDiana Whitaker-MenezesMarina Domingo-VidalMegan RocheKavitha RamaswamyDouglas C. HooperBonita FalknerMaria P. Martinez CantarinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Cristina Martos-Rus
Goni Katz-Greenberg
Zhao Lin
Eurico Serrano
Diana Whitaker-Menezes
Marina Domingo-Vidal
Megan Roche
Kavitha Ramaswamy
Douglas C. Hooper
Bonita Falkner
Maria P. Martinez Cantarin
Macrophage and adipocyte interaction as a source of inflammation in kidney disease
description Abstract In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.
format article
author Cristina Martos-Rus
Goni Katz-Greenberg
Zhao Lin
Eurico Serrano
Diana Whitaker-Menezes
Marina Domingo-Vidal
Megan Roche
Kavitha Ramaswamy
Douglas C. Hooper
Bonita Falkner
Maria P. Martinez Cantarin
author_facet Cristina Martos-Rus
Goni Katz-Greenberg
Zhao Lin
Eurico Serrano
Diana Whitaker-Menezes
Marina Domingo-Vidal
Megan Roche
Kavitha Ramaswamy
Douglas C. Hooper
Bonita Falkner
Maria P. Martinez Cantarin
author_sort Cristina Martos-Rus
title Macrophage and adipocyte interaction as a source of inflammation in kidney disease
title_short Macrophage and adipocyte interaction as a source of inflammation in kidney disease
title_full Macrophage and adipocyte interaction as a source of inflammation in kidney disease
title_fullStr Macrophage and adipocyte interaction as a source of inflammation in kidney disease
title_full_unstemmed Macrophage and adipocyte interaction as a source of inflammation in kidney disease
title_sort macrophage and adipocyte interaction as a source of inflammation in kidney disease
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/bc495e9753f94b0790517583f240a4d3
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