Upregulation of bone morphogenetic protein GDF-3/Vgr-2 expression in adipose tissue of FABP4/aP2 null mice

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Abstract

High-fat-fed C57Bl/6J FABP4/aP2 null mice develop obesity but not the related hyperglycemia or hyperinsulinemia characteristic of type II diabetes. FABP4/aP2 protein's function to bind fatty acids in the adipocytes may promote total body energy homeostasis by linking energy depots to the ability to express signaling molecules similar to leptin. To test this hypothesis, proteomic analysis of serum proteins from high-fat-fed wild-type and FABP4/aP2 null mice revealed that the GDF-3/Vgr-2 protein, a bone morphogenetic protein, was upregulated in C57Bl/6J FABP4/aP2 null mice. The increase in serum GDF-3/Vgr-2 protein was correlated with a 27-fold increase in adipose GDF-3/Vgr-2 mRNA. In contrast, leptin expression was unaltered between FABP4/aP2 null and wild-type animals. The expression of GDF-3/Vgr-2 mRNA was not substantially different in adipose tissue of db/db and tb/tb mice compared to wild-type controls. The expression of GDF-3/Vgr-2 mRNA was dependent upon the age and diet of the animals, declining as a function of age in high-fat-fed wild-type animals while increasing in the FABP4/aP2 null strain. These results identify GDF-3/Vgr-2 as an age- and fat-regulated, adipose-derived cytokine suggesting a linkage between adipocyte fatty acid metabolism and the expression of the bone morphogenetic family of differentiation regulators.

Original languageEnglish (US)
Pages (from-to)129-135
Number of pages7
JournalCytokine
Volume14
Issue number3
DOIs
StatePublished - May 7 2001

Bibliographical note

Funding Information:
We would like to thank the members of the Bernlohr laboratory, particularly Dr Ann Hertzel and Ms Jun Liu for their assistance with glucose and insulin measurements. Also, we would particularly like to thank Tom Krick, Director of the Minnesota Mass Spectrometry Core Facility (NSF 9871237) for his assistance with analysis of peptides by MALDI-TOF. This work was supported, in part, by the NIH (DK53189) and ADA (RA0004) to DAB and the Minnesota Obesity Center (NIH DK-50456) to BAW.

Keywords

  • Adipose tissue
  • Fatty acid binding protein
  • GDF-3/Vgr-2
  • Proteomics

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