Adipogenesis and glycemic improvement can be concurrent, yet independent (133.7)

Abstract

Although excessive adiposity is linked with impaired glycemic control, in some animal models transgenic manipulations that increase adiposity, paradoxically improve glycemic control. In mice, Ad36, ‐a human adenovirus, promotes adipogenesis, and enhances glycemic control. The E4orf1 gene of Ad36 is sufficient to improve diet induced hyperglycemia in mice, which offers therapeutic potential. Studies indicate that via E4orf1, Ad36 increases Ras to up‐regulate PPARγ and Glut4 signaling, leading to adipogenesis and better glycemic control, respectively. Our objective was to determine if the adipogenic and glycemic signaling pathways induced by E4orf1 are interdependent. PPARγ null mouse embryonic fibroblasts were transfected with vector expressing E4orf1 or a null vector. Compared to cells transfected with the null vector, E4orf1 expression significantly increased glucose uptake despite a complete absence of PPARγ or adipogenesis, and significantly enhanced Ras activation and the protein abundance of glucose transporters Glut4, Glut1 and adiponectin. Thus, E4orf1 can enhance the signaling underlying glucose disposal, independent of adipogenic signaling. This offers the possibility to harness the anti‐diabetic property of E4orf1, without its adipogenic effect. Moreover, conceptually, these results suggest that adipogenesis and glycemic improvement can be concurrent, yet independent.Grant Funding Source: Vital Health Interventions