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

High-fat-fed C57B1/6J FABP4/aP2 null mice develop obesity but not the relat ed hyperglycemia or hyperinsulinemia characteristic of type U[ diabetes. FA BP4/aP2 protein's function to bind fatty acids in the adipocytes may promot e total body energy homeostasis by linking energy depots to the ability to express signaling molecules similar to leptin, To test this hypothesis, pro teomic 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 prot ein, was upregulated in C57B1/6J 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/aP 2 null and wild-type animals, The expression of GDF-3/Vgr-2 mRNA was not su bstantially 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 regulato rs, (C) 2001 Academic Press.