Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha2-glycoprotein

Biochim Biophys Acta. 2004 Feb 27;1636(1):59-68. doi: 10.1016/j.bbalip.2003.12.004.


Loss of adipose tissue in cancer cachexia has been associated with tumour production of a lipid-mobilizing factor (LMF) which has been shown to be homologous with the plasma protein zinc-alpha(2)-glycoprotein (ZAG). The aim of this study was to compare the ability of human ZAG with LMF to stimulate lipolysis in vitro and induce loss of body fat in vivo, and to determine the mechanisms involved. ZAG was purified from human plasma using a combination of Q Sepharose and Superdex 75 chromatography, and was shown to stimulate glycerol release from isolated murine epididymal adipocytes in a dose-dependent manner. The effect was enhanced by the cyclic AMP phosphodiesterase inhibitor Ro20-1724, and attenuated by freeze/thawing and the specific beta3-adrenoreceptor antagonist SR59230A. In vivo ZAG caused highly significant, time-dependent, decreases in body weight without a reduction in food and water intake. Body composition analysis showed that loss of body weight could be attributed entirely to the loss of body fat. Loss of adipose tissue may have been due to the lipolytic effect of ZAG coupled with an increase in energy expenditure, since there was a dose-dependent increase in expression of uncoupling protein-1 (UCP-1) in brown adipose tissue. These results suggest that ZAG may be effective in the treatment of obesity.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipose Tissue / metabolism*
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Body Composition
  • Body Weight / drug effects
  • Carrier Proteins / analysis
  • Carrier Proteins / metabolism
  • Cells, Cultured
  • Humans
  • Ion Channels
  • Lipolysis
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / metabolism
  • Mice
  • Mitochondrial Proteins
  • Seminal Plasma Proteins / isolation & purification
  • Seminal Plasma Proteins / pharmacology
  • Seminal Plasma Proteins / physiology*
  • Uncoupling Protein 1


  • Carrier Proteins
  • Ion Channels
  • Membrane Proteins
  • Mitochondrial Proteins
  • Seminal Plasma Proteins
  • UCP1 protein, human
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Zn-alpha-2-glycoprotein