抄録
White adipose tissue plays an important metabolic role by storing triacylglycerol in periods of energy excess and releasing free fatty acids and glycerol during energy deprivation. Furthermore, adipocytes secrete a number of hormones that regulate metabolic homeostasis. The process of adipocyte differentiation has been characterized in cultures of cell lines of preadipocytes. In vitro adipogenesis requires a sequence of events, including growth arrest of proliferating preadipocytes, coordinated reentry into the cell cycle with limited clonal expansion, and growth arrest associated with terminal differentiation. Insulin and insulin-like growth factoir-1 promote differentiation of preadipocyes and it has been demonstrated that PI 3-kinase activity plays an important role in adipogenesis. However, the mechanism by which the PI 3-kinase /Akt signal is relayed to the nucleus to activate adipocyte differentiation is unknown. Akt phosphorylates the forkhead transcription factor Foxo1 and inhibits its transcriptional activity. Foxo1 is induced in the early stages of adipocyte differentiation but that its activation is delayed until the end of the clonal expansion stage. Constitutively active Foxo1 prevents the differentiation of preadipocyte due to early induction of cyclin-dependent kinase inhibitor, p21/Cip. In contrast, dominant-negative Foxo1 restores adipocyte differentiation of embryonic fibroblasts from insulin receptor-deficient mice. These data suggest that Foxo1 plays an important role in the integration of hormone-activated signaling pathway with the complex transcriptional cascade that promotes adipocyte differentiation. [Jpn J Physiol 54 Suppl:S7 (2004)]
