title: FDP-E induces adipocyte inflammation and suppresses insulin-stimulated glucose disposal: effect of inflammation and obesity on fibrinogen Bβ mRNA.
abstract: Obesity is associated with increased fibrinogen production and fibrin formation, which produces fibrin degradation products (FDP-E and FDP-D). Fibrin and FDPs both contribute to inflammation, which would be expected to suppress glucose uptake and insulin signaling in adipose tissue, yet the effect of FDP-E and FDP-D on adipocyte function and glucose disposal is completely unknown. We tested the effects of FDPs on inflammation in 3T3-L1 adipocytes and primary macrophages and adipocyte glucose uptake in vitro. High-fat-fed mice increased hepatic fibrinogen mRNA expression ninefold over chow-fed mice, with concomitant increases in plasma fibrinogen protein levels. Obese mice also displayed increased fibrinogen content of epididymal fat pads. We treated cultured 3T3-L1 adipocytes and primary macrophages with FDP-E, FDP-D, or fibrinogen degradation products (FgnDP-E). FDP-D and FgnDP-E had no effect on inflammation or glucose uptake. Cytokine mRNA expression in RAW264.7 macrophage-like cells and 3T3-L1 adipocytes treated with FDP-E induced inflammation with maximal effects at 100 nM and 6 h. Insulin-stimulated 2-deoxy-d-[(3)H]glucose uptake was reduced by 71% in adipocytes treated with FDP-E. FDP-E, but not FDP-D or FgnDP-E, induces inflammation in macrophages and adipocytes and decreases glucose uptake in vitro. FDP-E may contribute toward obesity-associated acute inflammation and glucose intolerance, although its chronic role in obesity remains to be elucidated.
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas;
authors.forename: Minsung
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Nutritional Sciences, Texas Tech University, Lubbock, Texas; Department of Exercise Science, High Point University, High Point, North Carolina; and.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Vaughan
authors.affiliation: Department of Food Science and Technology & Foods and Nutrition, University of Georgia, Athens, Georgia.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Paton
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000633:toxicity*; D005340:Fibrinogen / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis
chemical_list: C115499:BBeta fibrinogen; D005338:Fibrin Fibrinogen Degradation Products; D007328:Insulin; D012333:RNA, Messenger; D005340:Fibrinogen; D005947:Glucose
keywords: adipogenesis; glucose tolerance; inflammation; obesity; thrombosis