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 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-gamma (IFN-gamma) transcript levels. VAT demonstrated a broad leukocytosis relative to SAT that included macrophages, T cells and natural killer (NK) cells. IFN-gamma induced a proinflammatory cytokine expression pattern in SVF and adipose tissue macrophages (ATM). NK cells, which constitutively expressed IFN-gamma, were present at higher frequency in VAT relative to SAT. Both T and NK cells from SVF expressed IFN-gamma on activation, which was associated with tumor necrosis factor-alpha expression in macrophages.


CONCLUSIONS
These data suggest involvement of NK cells and IFN-gamma in regulating ATM phenotype and function in human obesity and a potential mechanism for the adverse physiologic effects of VAT.
O'Rourke
R W
RW
Department of Surgery, Oregon Health and Science University, Portland, OR 97239-3098, USA. orourkro@ohsu.edu
Metcalf
M D
MD
White
A E
AE
Madala
A
A
Winters
B R
BR
Maizlin
I I
II
Jobe
B A
BA
Roberts
C T
CT
Slifka
M K
MK
Marks
D L
DL
D000328:Adult; D050110:Bariatric Surgery; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D015434:Panniculitis / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*
D018836:Inflammation Mediators; D007371:Interferon-gamma