Wdnm1-like, a new adipokine with a role in MMP-2 activation

Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E205-15. doi: 10.1152/ajpendo.90316.2008. Epub 2008 May 20.


White adipose tissue functions in energy storage and as an endocrine organ. DNA microarray analysis led us to identify Wdnm1-like, a distant member of the whey acidic protein/four-disulfide core (WAP/4-DSC) family, as a differentiation-dependent gene in white and brown adipogenesis. Wdnm1-like is a novel 6.8-kDa protein, and Western blot analysis reveals secretion into culture media. Wdnm1-like transcript is selectively expressed in adipose tissue and liver and is enriched approximately 500-fold in white adipose depots vs. brown. Cellular fractionation of WAT demonstrates Wdnm1-like transcript expression is restricted to the adipocyte population. Studies in 3T3-L1 preadipocytes, an in vitro model of white adipogenesis, indicate Wdnm1-like transcript increases within 6 h of adipogenic induction with an approximately 17,000-fold increase by day 7. Dramatic upregulation of Wdnm1-like also accompanies white adipogenesis of ScAP-23 preadipocytes and primary preadipocytes. TNF-alpha treatment of 3T3-L1 adipocytes increased Wdnm1-like transcript level 2.4-fold and was attenuated by pretreatment with the p38 MAP kinase inhibitor SB203580. A number of WAP/4-DSC family proteins function as protease inhibitors. This, taken with the role of extracellular remodeling in adipogenesis, led us to address effects of Wdnm1-like on matrix metalloproteinase (MMP) activity. Gelatin zymography of HT1080 fibrosarcoma cells transfected with a Wdnm1-like expression construct revealed markedly increased levels of active MMP-2. Our findings identify a new member of the adipocyte "secretome" that functions to enhance MMP-2 activity. We postulate that Wdnm1-like may play roles in remodeling of the extracellular milieu in adipogenesis, as well as in tumor microenvironments where adipocytes are key stromal components.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes, Brown / enzymology
  • Adipocytes, Brown / metabolism
  • Adipogenesis / physiology
  • Adipokines / biosynthesis
  • Adipokines / genetics
  • Adipokines / metabolism*
  • Adipose Tissue, White / enzymology
  • Adipose Tissue, White / metabolism*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • Enzyme Activation
  • Male
  • Matrix Metalloproteinase 2 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Transcription, Genetic
  • Transfection


  • Adipokines
  • RNA, Messenger
  • Matrix Metalloproteinase 2