Advanced oxidation protein products induce inflammatory response and insulin resistance in cultured adipocytes via induction of endoplasmic reticulum stress

Qiu Gen Zhou, Min Zhou, Ai Ju Lou, Di Xie, Fan Fan Hou
Cellular Physiology and Biochemistry 2010, 26 (4-5): 775-86
Accumulation of advanced oxidation protein products (AOPPs) is prevalent in metabolic syndrome and type 2 diabetes. Adipocyte dysfunction has been recognized as a link between these conditions. To examine the effect of AOPPs on adipocyte perturbation, 3T3-L1 adipocytes were treated with increased levels of AOPPs as seen in these conditions. Exposure of adipocytes to AOPPs induced overexpression of tumor necrosis factor α and interleukin-6. This inflammatory response was completely blocked by nuclear factor-κB inhibitor SN50. AOPPs challenge also impaired insulin signaling, which was partly prevented by SN50. Treatment with AOPPs triggered endoplasmic reticulum (ER) stress, revealed by phosphorylation of PKR-like eukaryotic initiation factor 2α kinase, eukaryotic translational initiation factor 2α, inositol-requiring enzyme 1 and c-jun N-terminal kinase, and by overexpression of glucose regulated protein 78. AOPPs-induced ER stress was mediated by reactive oxygen species (ROS) generated by activation of NADPH oxidase since it was prevented by NADPH oxidase inhibitors or ROS scavenger. Treating the cells with inhibitors of NADPH oxidase or ER stress could completely abolish AOPPs-induced overexpression of adipocytokines and insulin resistance, suggesting that AOPPs induced adipocyte perturbation probably through induction of ROS-dependent ER stress. Our data identified AOPPs as a class of important mediator of adipocyte perturbation. Accumulation of AOPPs might be involved in adipocyte dysfunction as seen in metabolic syndrome and type 2 diabetes.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"