Depot-specific differences in inflammatory mediators and a role for NK cells and IFN-gamma in inflammation in human adipose tissue

Background: Adipose tissue is a primary in vivo site of inflammation in obesity. Excess visceral adipose tissue (VAT), when compared to subcutaneous adipose tissue (SAT), imparts an increased risk of obesity-related comorbidities and mortality, and exhibits differences in inflammation. Defining depo...

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Vydáno v:International Journal of Obesity Ročník 33; číslo 9; s. 978 - 990
Hlavní autoři: O'Rourke, R.W, Metcalf M.D, White, A.E, Madala, A, Winters, B.R, Maizlin, I.I, Jobe, B.A, Roberts, C.T. Jr, Slifka, M.K, Marks, D.L
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 01.09.2009
Nature Publishing Group
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ISSN:0307-0565, 1476-5497, 1476-5497
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Shrnutí:Background: Adipose tissue is a primary in vivo site of inflammation in obesity. Excess visceral adipose tissue (VAT), when compared to subcutaneous adipose tissue (SAT), imparts an increased risk of obesity-related comorbidities and mortality, and exhibits differences in inflammation. Defining depot-specific differences in inflammatory function may reveal underlying mechanisms of adipose-tissue-based inflammation. Methods: Stromovascular cell fractions (SVFs) from VAT and SAT from obese humans undergoing bariatric surgery were studied in an in vitro culture system with transcriptional profiling, flow cytometric phenotyping, enzyme-linked immunosorbent assay and intracellular cytokine staining. Results: Transcriptional profiling of SVF revealed differences in inflammatory transcript levels in VAT relative to SAT, including elevated interferon- (IFN-) transcript levels. VAT demonstrated a broad leukocytosis relative to SAT that included macrophages, T cells and natural killer (NK) cells. IFN- induced a proinflammatory cytokine expression pattern in SVF and adipose tissue macrophages (ATM). NK cells, which constitutively expressed IFN-, were present at higher frequency in VAT relative to SAT. Both T and NK cells from SVF expressed IFN- on activation, which was associated with tumor necrosis factor- expression in macrophages. Conclusion: These data suggest involvement of NK cells and IFN- in regulating ATM phenotype and function in human obesity and a potential mechanism for the adverse physiologic effects of VAT.
Bibliografie:http://dx.doi.org/10.1038/ijo.2009.133
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ISSN:0307-0565
1476-5497
1476-5497
DOI:10.1038/ijo.2009.133