Regulation of adipocyte fatty acid binding protein (a-FABP) gene expression during the early events of adipocyte differentiation

Abstract

The conversion of preadipocytes to adipocytes is stimulated by the insulin growth factor 1 (IGF-1) and appears to be one of the consequences of insulin resistance seen in patient suffering from obesity and non insulin dependent diabetes milletus (NIDDM). The study of the adipocyte specific gene a-FABP has yielded important information regarding the molecular mechanisms regulating adipocyte differentiation. One of the most significant contribution was the discovery of the adipogenic transcription factor mPPARγ2. Original studies suggested that an increase in mPPARγ2 expression was sufficient to trigger the adipogenic program, and this event was amplified by ligand activation. The work presented here tested the timely expression of mPPARγ2 and of RXRα, its binding partner, during the early event of fat cell terminal differentiation. Our work suggest a novel regulatory mechanism for the control of expression of genes that are target for mPPARγ2 and more precisely for aFABP. An increase in mPPARγ2 was detectable but an increase in RXRα protein expression appeared to be the key regulatory event for the activation of the heterodimer. During the process of studying these events we also characterized a novel 3T3-L1 derivative cell line that contained a defective signaling system which did not permit ligand activation of mPPARγ2 and terminal differentiation.