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 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.
Type
Journal articleSubject
Adipose TissueCells, Cultured
3T3-L1 Cells
Adipocytes
Macrophages
Animals
Humans
Mice
Kidney Failure, Chronic
Uremia
Obesity
Inflammation
Inflammation Mediators
Cytokines
Coculture Techniques
Case-Control Studies
Cell Communication
Lipolysis
Male
Primary Cell Culture
RAW 264.7 Cells
THP-1 Cells
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https://hdl.handle.net/10161/25727Published Version (Please cite this version)
10.1038/s41598-021-82685-4Publication Info
Martos-Rus, Cristina; Katz-Greenberg, Goni; Lin, Zhao; Serrano, Eurico; Whitaker-Menezes,
Diana; Domingo-Vidal, Marina; ... Martinez Cantarin, Maria P (2021). Macrophage and adipocyte interaction as a source of inflammation in kidney disease.
Scientific reports, 11(1). pp. 2974. 10.1038/s41598-021-82685-4. Retrieved from https://hdl.handle.net/10161/25727.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Goni Katz-Greenberg
Assistant Professor of Medicine

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