FIGURE 4.

Beneficial and detrimental phenotypes of altering OGT, OGA, and GFAT. GFAT upregulation in skeletal muscle, fat, the liver, or β cells caused metabolic dysfunction and exacerbated hypertrophy after pressure overload in cardiomyocytes. GFAT knockout in cardiomyocyte attenuated hypertrophy after pressure overload. The cardiomyocyte phenotypes are associated with change of protein O-GlcNAcylation and mTOR activity. Ogt knockout or Oga knockout/dominant negative expression have both detrimental effects (mostly on tissue pathologies) and beneficial effects (on metabolism or learning and memory). Oga upregulation through AAV-i.v. injections seems to attenuate left ventricle remodeling in diabetic mice. Red highlights detrimental effects, and blue highlights beneficial effects.