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

Nephrol Dial Transplant. 2012 Aug;27(8):3119-29. doi: 10.1093/ndt/gfr774. Epub 2012 Jan 28.

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 transcription-polymerase 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipokines / blood
  • Adipokines / genetics
  • Adipose Tissue / metabolism
  • Adipose Tissue / pathology
  • Animals
  • Base Sequence
  • DNA Primers / genetics
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / pathology
  • Dialysis Solutions / adverse effects*
  • Inflammation / etiology
  • Inflammation / metabolism
  • Interleukin-6 / metabolism
  • Leptin / blood
  • Leptin / genetics
  • Leptin / metabolism*
  • MAP Kinase Signaling System
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Peritoneal Dialysis, Continuous Ambulatory / adverse effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Leptin / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Adipokines
  • DNA Primers
  • Dialysis Solutions
  • Interleukin-6
  • Leptin
  • RNA, Messenger
  • Receptors, Leptin
  • Tumor Necrosis Factor-alpha