White adipose tissue overproduces the lipid-mobilizing factor zinc α2-glycoprotein in chronic kidney disease

Kidney Int. 2013 May;83(5):878-86. doi: 10.1038/ki.2013.9. Epub 2013 Feb 20.


Chronic kidney disease (CKD) is frequently associated with protein-energy wasting, a recognized strong predictive factor of mortality. Zinc α2-glycoprotein (ZAG) is a new adipokine involved in body weight control through its lipid-mobilizing activity. Here we tested whether the uremic environment in CKD could alter ZAG production by white adipose tissue and contribute to CKD-associated metabolic disturbances. Compared with normal plasma, uremic plasma induced a significant increase in ZAG synthesis (124%), was associated with a significant increase in basal lipolysis (31%), and significantly blunted lipogenesis (-53%) in 3T3-L1 adipocytes in vitro. In 5/6 nephrectomized rats and mice in vivo, there was a significant decrease in white adipose tissue accretion (-44% and -43%, respectively) and a significantly higher white adipose tissue content of ZAG protein than in sham-operated, pair-fed control animals (498% and 106%, respectively). Subcutaneous white adipose tissue biopsies from patients with end-stage renal disease exhibited a higher content of ZAG (573%) than age-matched controls. Thus, the ZAG content is increased in white adipose tissue from patients or animal models with CKD. Overproduction of ZAG in CKD could be a major contributor to metabolic disturbances associated with CKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipokines
  • Adipose Tissue, White / metabolism*
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biopsy
  • Carrier Proteins / blood*
  • Case-Control Studies
  • Disease Models, Animal
  • Female
  • Glycoproteins / blood*
  • Humans
  • Kidney Failure, Chronic / blood
  • Lipogenesis
  • Lipolysis
  • Male
  • Mice
  • Middle Aged
  • Peritoneal Dialysis
  • Rats
  • Rats, Wistar
  • Renal Dialysis
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / therapy
  • Up-Regulation
  • Uremia / blood


  • AZGP1 protein, human
  • Adipokines
  • Carrier Proteins
  • Glycoproteins