Glucose-based peritoneal dialysis solution suppresses adiponectin synthesis through oxidative stress in an experimental model of peritoneal dialysis.
OBJECTIVE
Accumulation of visceral fat is one of the major risk factors for the development of cardiovascular disease in peritoneal dialysis (PD) patients. Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic disease, is reported to be downregulated in its gene level in end-stage renal disease patients. Since excessive fat deposit is involved in increased reactive oxygen species (ROS), PD solution (PDS) may contribute to ROS production, resulting in dysregulation of adiponectin. In this study, we tested our hypothesis that oxidative stress induced by PDS may play a role in the regulation of adiponectin.


METHODS
Commercial PDS containing 3.86% glucose (20 - 30 mL) was administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10 mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate. For in vitro studies, fully differentiated 3T3-L1 adipocytes and adipocytes isolated from abdominal fat were treated with a high glucose solution, PDS, and H(2)O(2). Adiponectin levels in the conditioned media were measured by ELISA and immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were examined using real-time RT-PCR.


RESULTS
The levels of adiponectin in plasma and spent dialysate were significantly downregulated by PDS and this effect was suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by 50 mmol/L glucose, PDS diluted 2-fold, and H(2)O(2) (200 μmol/L). In addition, H(2)O(2) downregulated expression of adiponectin mRNA and secretion of adiponectin oligomer complexes.


CONCLUSIONS
Our data suggest that ROS induced by conventional glucose-based PDS may contribute to pathophysiological changes in abdominal fat and downregulate adiponectin secreted from adipocytes during long-term PD.
Huh
Joo Young
JY
Division of Life and Pharmaceutical Sciences, Department of Bioinspired Science, College of Pharmacy, Ewha Womans University, Seoul, Korea.
Seo
Eun-Young
EY
Lee
Hi Bahl
HB
Ha
Hunjoo
H
D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D052242:Adiponectin / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D015314:Dialysis Solutions / Q000008:administration & dosage*; D019468:Disease Management; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000008:administration & dosage*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013549:Sweetening Agents / Q000494:pharmacology
D052242:Adiponectin; D015314:Dialysis Solutions; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013549:Sweetening Agents; D005947:Glucose
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