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

dc.contributor.author

Martos-Rus, Cristina

dc.contributor.author

Katz-Greenberg, Goni

dc.contributor.author

Lin, Zhao

dc.contributor.author

Serrano, Eurico

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Whitaker-Menezes, Diana

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Domingo-Vidal, Marina

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Roche, Megan

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Ramaswamy, Kavitha

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Hooper, Douglas C

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Falkner, Bonita

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Martinez Cantarin, Maria P

dc.date.accessioned

2022-09-20T21:06:46Z

dc.date.available

2022-09-20T21:06:46Z

dc.date.issued

2021-02-03

dc.date.updated

2022-09-20T21:06:42Z

dc.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.

dc.identifier

10.1038/s41598-021-82685-4

dc.identifier.issn

2045-2322

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2045-2322

dc.identifier.uri

https://hdl.handle.net/10161/25727

dc.language

eng

dc.publisher

Springer Science and Business Media LLC

dc.relation.ispartof

Scientific reports

dc.relation.isversionof

10.1038/s41598-021-82685-4

dc.subject

Adipose Tissue

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Cells, Cultured

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3T3-L1 Cells

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Adipocytes

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Macrophages

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Animals

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Humans

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Mice

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Kidney Failure, Chronic

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Uremia

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Obesity

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Inflammation

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Inflammation Mediators

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Cytokines

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Coculture Techniques

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Case-Control Studies

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Cell Communication

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Lipolysis

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Male

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Primary Cell Culture

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RAW 264.7 Cells

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THP-1 Cells

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Katz-Greenberg, Goni|0000-0003-4780-4156

pubs.begin-page

2974

pubs.issue

1

pubs.organisational-group

Duke

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School of Medicine

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Clinical Science Departments

pubs.organisational-group

Medicine

pubs.organisational-group

Medicine, Nephrology

pubs.publication-status

Published

pubs.volume

11

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