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Proinflammatory adipocytokines induce TIMP‐1 expression in 3T3‐L1 adipocytes
Author(s) -
Kralisch Susan,
Klein Johannes,
Lossner Ulrike,
Bluher Matthias,
Paschke Ralf,
Stumvoll Michael,
Fasshauer Mathias
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.10.033
Subject(s) - adipokine , proinflammatory cytokine , 3t3 l1 , microbiology and biotechnology , medicine , chemistry , endocrinology , adipocyte , biology , inflammation , leptin , adipose tissue , obesity
Tissue inhibitor of metalloproteinase (TIMP)‐1 is an adipocyte‐secreted protein upregulated in obesity which promotes adipose tissue development. Furthermore, the proinflammatory adipocytokines tumor necrosis factor α (TNFα) and interleukin (IL)‐6 induce insulin resistance, and plasma concentrations are increased during weight gain. In the current study, the impact of TNFα and IL‐6 on TIMP‐1 mRNA and protein expression was determined in 3T3‐L1 adipocytes. Interestingly, TNFα and IL‐6 induced TIMP‐1 protein secretion more than 3‐ and 2‐fold, respectively. Furthermore, TIMP‐1 mRNA was upregulated in a time‐ and dose‐dependent fashion. Inhibitor experiments suggested that nuclear factor κB and p44/42 mitogen‐activated protein kinase are involved in both, basal and adipocytokine‐induced TIMP‐1 expression. Moreover, the thiazolidinedione troglitazone partly reversed TNFα‐ but not IL‐6‐induced TIMP‐1 synthesis. Taken together, we demonstrate that TIMP‐1 expression is selectively upregulated in fat cells by proinflammatory adipocytokines and might play a role in maintaining adipose tissue mass in obesity.