From Preadipocyte to Adipocyte: Differentiation-Directed Signals of Insulin from the Cell Surface to the Nucleus

Abstract

An alarming rise in obesity, and the accompanying threat of type 2 diabetes mellitus and cardiovascular disease, have attracted worldwide attention. The pathogenic mechanism(s) underlying obesity remains obscure. However, new cellular and molecular insights about the development of adipose tissue, with respect to adipocyte number (hyperplasia) and size (hypertrophy), are occurring at a rapid pace. Specialized fibroblasts (preadipocytes) committed to the adipocyte lineage are present throughout life. Primary cell culture systems and immortalized cell line models of preadipocytes have advanced the study of adipocyte differentiation (adipogenesis). Differentiation-inducing cues are able to trigger a complex network of intracellular signaling pathways in the preadipocyte, allowing signals from cell-surface receptors to reach nuclear transcription factors that regulate the genetic program of adipocyte differentiation. The extracellular matrix environment of the preadipocyte, known to modulate adipogenesis, may act by altering some of these signaling events.

KEYWORDS: :

• obesity
• adipocyte differentiation
• preadipocyte
• insulin
• insulin-like growth factor-1
• phosphatidylinositol 3-kinase
• protein kinase B
• p70 S6 kinase
• Ras
• extracellular matrix.