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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/E869    most recent 91011.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhou, Q. G. Articles by Peng, X. Search for Related Content PubMed PubMed Citation Articles by Zhou, Q. G. Articles by Peng, X.

Asymmetrical dimethylarginine triggers lipolysis and inflammatory response via induction of endoplasmic reticulum stress in cultured adipocytes

Division of Nephrology, Nanfang Hospital, Southern Medical University, Key Laboratory of Organ Failure, Ministry of Education, Guangzhou, China

Submitted 18 December 2008 ; accepted in final form 3 February 2009

Protein energy wasting, a state of decreased stores of body protein and fat, is a risk factor for mortality in advanced chronic kidney disease (CKD). Little is known about the mechanism underlying loss of fat in CKD. Accumulation of asymmetric dimethylarginine (ADMA) is prevalent in advanced CKD. Here we assessed the effect of ADMA on cellular perturbation in cultured 3T3-L1 adipocytes. Exposure of adipocytes to ADMA induced lipolysis and decreased perilipin A, with no alteration of lipases expression or activity. ADMA treatment also upregulated the expression of inflammatory adipocytokines via activation of nuclear factor-B (NF-B). Blocking the inflammatory responses with NF-B inhibitor partly inhibited the ADMA-induced lipolysis. Furthermore, ADMA treatment triggered endoplasmic reticulum (ER) stress, revealed by phosphorylation of PKR-like eukaryotic initiation factor 2 kinase, eukaryotic translational initiation factor 2, c-Jun NH₂-terminal kinase, and overexpression of glucose-regulated protein 78. Treatment with ER stress inhibitor completely abolished the ADMA-induced lipolysis and inflammatory responses. Moreover, conditioned medium from the ADMA-treated adipocytes increased protein degradation in cultured C₂C₁₂ myotubes, suggesting that the ADMA-induced adipocyte perturbation may promote skeletal muscle proteolysis. These data suggest that elevated ADMA promoted the adipocyte perturbation through induction of ER stress, which might have implication for protein energy wasting in CKD.

asymmetric dimethylarginine; adipocytes; lipolysis; inflammatory response; endoplasmic reticulum stress; protein energy wasting