The G(s alpha)/G(i alpha 2) axis controls adipogenesis independently of adenylylcyclase

Adipogenesis is the commitment of embryonic stem cells to the highly-differentiated phenotype of the adipocyte, a cell specialized to regulate. in a dynamic fashion, lipid storage. The mouse embryonic 3T3-L1 fibroblasts provide a useful model in which to probe the control of differentiation in general and adipogenesis in particular. The G-proteins G(s alpha) and G(i alpha 2), have been shown to modulate commitment of fibroblasts to adipocytes in response to inducers such as dexamethasone and methylisobutylxanthine. Cellular levels of G(s alpha) decline sharply in response to inducers as cells commit to the adipogenic phenotype. The molecular strategies of antisense DNA technology and expression of constitutively-activated mutants of G(i alpha 2) reveal that either suppression of G(s alpha) or expression of constitutively-active G(i alpha 2) dramatically accelerate the ability of inducers to stimulate adipogenesis or act as inducers themselves. These roles of Gs alpha and G(i alpha 2) are expressed in ambient or elevated intracellular cyclic AMP, demonstrating a critical role of G-proteins in cellular differentiation independent of adenylylcyclase.