Disease relevance of Gdf3

• Vgr-2 is expressed in F9 teratocarcinoma cells, and its RNA levels are down-regulated within 24 h after differentiation with retinoic acid [1].
• Mice transduced with GDF-3 displayed profound weight gain when fed with high fat diet [2].
• To identify its biological function, GDF-3 was overexpressed in mice by adenovirus mediated gene transfer [2].
• However, GDF-3 was not involved in blood glucose homeostasis or insulin resistance, a condition associated with obesity [2].
• Herein we investigate the physiological and molecular mechanisms that underlie this protection from diet-induced obesity and demonstrate that GDF3 deficiency selectively affects white adipose through its influence on basal metabolic rates [3].

High impact information on Gdf3

• In both human and mouse embryonic stem cells, a member of this family, GDF3, is specifically expressed in the pluripotent state [4].
• By Northern analysis, GDF-3 transcripts were detected primarily in adult bone marrow, spleen, thymus, and adipose tissue [5].
• Unlike all previously described members of this superfamily, both GDF-3 and GDF-9 lack the conserved cysteine residue that is believed to form the sole disulfide linkage between subunits in other family members [5].
• The genomic organization of Vgr-2 and its location on mouse chromosome 6 are reported [1].
• A cDNA clone, Vgr-2, with homology to certain members of the transforming growth factor-beta superfamily has been isolated from a mouse embryo cDNA library [1].

Biological context of Gdf3

• GDF-3 stimulated peroxisome proliferator activated receptor expression in adipocytes, a master nuclear receptor that controls adipogenesis [2].
• In contrast, similar phenotypes were not observed in GDF-3 mice fed with normal chow, indicating that GDF-3 is only active under high lipid load [2].
• Upregulation of bone morphogenetic protein GDF-3/Vgr-2 expression in adipose tissue of FABP4/aP2 null mice [6].

Anatomical context of Gdf3

• 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 [6].

References