title: 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 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.
  
  
  CONCLUSIONS
  In conclusion, PD-induced hyperleptinemia amplifies the inflammatory response of adipose tissue through short-form leptin receptor when the long-form isotype is defective.
authors.affiliation: Department of Medicine, Queen Mary Hospital, University of Hong Kong, Pokfulam, Hong Kong. jckleung@hku.hk
authors.forename: Joseph C K
authors.initials: JC
authors.lastname: Leung
authors.forename: Loretta Y Y
authors.initials: LY
authors.lastname: Chan
authors.forename: Man Fai
authors.initials: MF
authors.lastname: Lam
authors.forename: Sydney C W
authors.initials: SC
authors.lastname: Tang
authors.forename: Chui Wa
authors.initials: CW
authors.lastname: Chow
authors.forename: Ai Ing
authors.initials: AI
authors.lastname: Lim
authors.forename: Kar Neng
authors.initials: KN
authors.lastname: Lai
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D054392:Adipokines / Q000097:blood / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015314:Dialysis Solutions / Q000009:adverse effects*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054392:Adipokines; D017931:DNA Primers; D015314:Dialysis Solutions; D015850:Interleukin-6; D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; D014409:Tumor Necrosis Factor-alpha