Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney disease

Nephrol Dial Transplant. 2007 Jan;22(1):171-8. doi: 10.1093/ndt/gfl552. Epub 2006 Sep 27.

Abstract

Background: Despite the favourable effects of adiponectin on the vasculature and insulin resistance (IR), levels are increased in patients with end-stage kidney disease (ESKD), in whom both IR and atherosclerosis are prevalent.

Methods: To investigate this paradox, we examined the distribution of adiponectin isoforms, the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched controls, and its function by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation of AdipoR on PBMC. We also compared the expression of AdipoR on PBMC with that on muscle and subcutaneous and visceral fat in 10 patients undergoing elective cholecystectomy.

Results: The proportion of the high molecular weight (HMW) isoform of adiponectin was increased in the dialysis group (P = 0.001), even though these patients were significantly insulin resistant compared with controls (P = 0.006). AdipoR1 and AdipoR2 on PBMC were also increased in patients with ESKD (P < 0.05 and P = 0.007, respectively), but levels did not correlate with IR, the HMW isoform or other anthropometric measurements. There was a strong correlation between AdipoR1 and AdipoR2 on PBMC in ESKD and in subcutaneous and visceral fat in controls. However, there was no relationship between AdipoR in PBMC, muscle or visceral fat. Phosphorylation of AMPK by recombinant adiponectin showed that AdipoR on PBMC, from controls and ESKD patients, were equally functional.

Conclusions: IR in ESKD is not explained by the change in isoformic distribution, or by AdipoR down-regulation or dysfunction. Rather, this receptor-ligand axis is up-regulated and may be a beneficial response to the inflammatory milieu of ESKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Adiponectin / biosynthesis*
  • Adiponectin / blood
  • Adiponectin / chemistry
  • Adolescent
  • Adult
  • Aged
  • Atherosclerosis / complications
  • Atherosclerosis / metabolism
  • Humans
  • Insulin Resistance
  • Kidney Failure, Chronic / diagnosis*
  • Kidney Failure, Chronic / metabolism*
  • Leukocytes, Mononuclear / cytology
  • Middle Aged
  • Multienzyme Complexes / biosynthesis
  • Phosphorylation
  • Protein Isoforms
  • Protein Serine-Threonine Kinases / biosynthesis
  • Receptors, Adiponectin
  • Receptors, Cell Surface / biosynthesis
  • Up-Regulation*

Substances

  • ADIPOR1 protein, human
  • Adiponectin
  • Multienzyme Complexes
  • Protein Isoforms
  • Receptors, Adiponectin
  • Receptors, Cell Surface
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases