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The influence of inflammation on the human visceral adipose tissue secretome
Author(s) -
Vonk Roel J.,
Szalowska Ewa,
Weening Desiree,
Vries Marcel,
Hoek Annemieke,
Roelofsen Han
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.659.16
Subject(s) - adipose tissue , inflammation , chemokine , secretion , adipokine , tumor necrosis factor alpha , interleukin 8 , immune system , proteome , chemistry , adipose tissue macrophages , biology , biochemistry , insulin resistance , immunology , endocrinology , white adipose tissue , insulin
Chronic inflammation of obese adipose tissue is involved in the development of insulin resistance and type 2 diabetes, probably via altered secretion of adipokines and free fatty acids. To determine how inflammation changes the adipose tissue secretome, adipose tissue was challenged with LPS, a potent immune activator. Secretome changes were analyzed by a quantitative proteomics approach: Comparison of Isotope Labeled Amino acid Incorporation Rates (CILAIR). CILAIR compares incorporation rates of 13C‐labeled lysine in secreted proteins between conditions (Mol Cell Proteomics 2009, 8:316). Methods Human visceral adipose tissue was divided over six dishes. 13C‐Lys containing medium was added and to three dishes also LPS (100 μg/ml). Dishes were incubated for 24 hrs. Media were collected and processed separately, involving SDS‐PAGE fractionation, in‐gel digestion of excised bands and LC‐MS/MS. Database searching with ProteinPilot (Applied Biosystems) provided identifications and C13/C12 ratios. Results 37 proteins were significantly changed (p<0.05) in expression of which 19 were up‐regulated by LPS and 19 were down‐regulated. Examples of up‐regulated proteins are: Plasminogen activator inhibitor 2, Growth‐regulated alpha protein and Interleukin‐6. In addition, 12 proteins were only expressed in the inflammatory condition. Examples are: Tumor necrosis factor‐α and C‐C motif chemokine 2 and 20. Conclusion These results indicate that inflammation profoundly changes the adipose tissue secretome. Secretion of several inflammatory cytokines and chemokines was up‐regulated as well as proteins involved in cell adhesion of attracted immune cells. These findings may have implications for the regulation of whole body insulin sensitivity and energy metabolism.