Amyloid precursor protein expression is induced by tumor necrosis factor alpha in 3T3-L1 adipocytes.
Amyloid precursor protein (APP) has been characterized as an adipocyte-secreted protein that might contribute to obesity-related insulin resistance, inflammation, and dementia. In the current study, regulation of APP by the proinflammatory and insulin resistance-inducing cytokine tumor necrosis factor (TNF) alpha was determined in 3T3-L1 adipocytes. Interestingly, APP protein synthesis and mRNA expression were significantly increased by TNFalpha in a time-dependent manner with maximal induction observed after 24 h of treatment. Furthermore, TNFalpha induced APP mRNA expression dose-dependently with maximal 6.4-fold upregulation seen at 100 ng/ml effector. Moreover, inhibitor experiments suggested that TNFalpha-induced APP expression was mediated by nuclear factor kappa B. Taken together, we show for the first time a potent upregulation of APP by TNFalpha suggesting a potential role of this adipocyte-secreted protein in TNFalpha-induced insulin resistance and inflammatory disease.
Department of Internal Medicine III, University of Leipzig, 04103 Leipzig, Germany.
Grit
G
Sommer
Susan
S
Kralisch
Jana
J
Lipfert
Sebastian
S
Weise
Kerstin
K
Krause
Beate
B
Jessnitzer
Ulrike
U
Lössner
Matthias
M
Blüher
Michael
M
Stumvoll
Mathias
M
Fasshauer
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha