2016-11-142013-05-242016-11-142013-05http://hdl.handle.net/2346/ETD-TTU-2013-05-1172http://hdl.handle.net/2346/48905Obesity, the most predominant disease in the world, is strongly associated with chronic inflammation which is directly correlated with insulin resistance (IR). Obesity also results in hyperfibrinogenemia. Fibrinogen, a glycoprotein involved in coagulation, is converted to fibrin via thrombin to form a blood clot and fibrin is degraded into two D (FDP-D) and one E (FDP-E) fragment by plasmin. Previous studies show that fibrinogen and fibrin induce inflammation but effect of FDP is unknown. FDP-D is used as a biomarker of hypercoagulability and has less bioactivity so we decided to focus on examining the effect of FDP-E on inflammation and adipocyte glucose disposal. First, cytokine mRNA expression in primary macrophages treated with FDP-E was measured and the results showed that FDP-E induces inflammation (55.9±7.1 fold change in MCP-1). RAW264.7 macrophages and 3T3-L1 adipocytes were treated with FDP-E from 0- to 100nM or for different times from 1 to 12 hours. FDP-E had the greatest effect at 100nM for 6 hours in both macrophages (29.5±9.8 fold change in MCP-1) and adipocytes (11.3±3.1 fold change in MCP-1). Next, adipocytes were treated with increasing concentrations of conditioned medium from FDP-E treated macrophages or FDP-E itself to assess the indirect or direct effects on glucose uptake. After 24 hours, the capacity for glucose uptake using radiolabeled 3H-2-deoxy-D-glucose was determined. There was no significant difference in conditioned medium treated cells but FDP-E itself suppressed insulin stimulated glucose uptake significantly (71% reduction; p=0.00001). We found that FDP-E induces inflammation in macrophages and adipocytes and decreases glucose uptake in adipocytes. From these results, we can conclude that FDP-E could be a key molecule in obesity, inflammation, and insulin resistance.application/pdfengObesityChronic inflammationInsulin resistanceFDP-EThesis2346/ETD-TTU-2013-05-1172