The role of leptin and its short-form receptor in inflammation in db/db mice infused with peritoneal dialysis fluid

Abstract

Background. In peritoneal dialysis (PD), the peritoneal membrane exhibits structural and functional changes following continuous exposure to the non-physiological peritoneal dialysis fluid (PDF). In this study, we examined the effect of PDF on peritoneal adipose tissue in a diabetic milieu. Methods. Six-week-old db/db mice and their non-diabetic littermates (db/m) were subjected to uninephrectomy. All animals then received intra-abdominal infusion of lactated Ringer's solution (Ringer) or 1.5 glucose-containing PDF (Dianeal) twice daily. Mice were sacrificed 4 weeks later. Parietal and visceral adipose tissues were harvested for examining gene and protein expression of adiponectin, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, tumor necrosis factor alpha (TNF-α), transforming growth factor beta and interleukin 6 (IL-6). Expression of TNF-α and F4/80 macrophage accumulation in adipose tissues was assessed by immunohistochemical staining. Modulation of leptin synthesis and leptin receptors expression and the relevant signaling pathways were also determined by quantitative reverse transcriptionpolymerase chain reaction, immunoblotting or enzyme-linked immunosorbent assay. Results. Compared to Ringer infusion, Dianeal infusion significantly increased serum leptin but decreased adiponectin in db/db mice. Increased expression of leptin, TNF-α and IL-6 was observed in visceral but not in parietal adipose tissue. Dianeal infusion also increased F4/80 macrophage accumulation and enhanced the expression of pro-inflammatory cytokines including IL-6 and TNF-α in the visceral adipose tissue. Compared to db/m mice, infusion with Dianeal exhibited a more deleterious effect on db/db mice, characterized by an upregulation of short-form leptin receptor ObRa and activation of the mitogen-activated protein kinase signaling pathway. Conclusion. In conclusion, PD-induced hyperleptinemia amplifies the inflammatory response of adipose tissue through short-form leptin receptor when the long-form isotype is defective. © The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.