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Obesity induced fibrinogen formation and its effect on adipocyte inflammation and glucose uptake
Author(s) -
Paton Chad M
Publication year - 2013
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.27.1_supplement.565.1
Subject(s) - fibrinogen , inflammation , medicine , endocrinology , adipose tissue , adipocyte , chemistry , proinflammatory cytokine , fibrin , adipose tissue macrophages , insulin resistance , fibrosis , insulin , white adipose tissue , biology , immunology
Obesity and insulin resistance are associated with increased fibrinogen production and inflammation, yet the effect of fibrin degradation products (FDP‐E and FDP‐D) on glucose disposal is completely unknown. We hypothesize that FDP‐E will decrease glucose disposal by increasing inflammation and cytokine production in macrophages. First, we determined the effect of obesity on fibrinogen expression and fibrin deposition. WT B6 mice fed a high fat diet for 15 weeks increased plasma fibrinogen content along with hepatic fibrinogen expression and FDP‐E content increased 4‐fold. Next, we injected FDP‐E directly into S.C fat which induced inflammation and apoptosis. In fibroblasts, FDP‐E reduced cell viability and induced pro‐fibrotic gene expression. 3T3‐L1 adipocytes were treated with FDP‐E or conditioned media (CM) from FDP‐E treated peritoneal macrophages. We found that FDP‐E and CM suppressed glucose uptake in adipocytes and caused a significant increase in M1 proinflammatory biomarkers such as TNF‐á and IL‐6 in macrophages and mature adipocytes with no appreciable effect on M2 antiinflammatory gene expression. Fibrinogen expression and deposition is increased with obesity. The increase in fibrinogen expression and fibrin deposition leads to increased adipocyte inflammation and macrophage infiltration which suppresses glucose uptake and may promote adipose tissue fibrosis.