PPARγ activators improve glucose homeostasis by stimulating fatty acid uptake in the adipocytes

It is currently thought that the effects of PPAR gamma activation on glucose homeostasis may be due to the effect of this nuclear receptor on the production of adipocyte-derived signalling molecules, which affect muscle glucose metabolism. Potential signalling molecules derived from adipocytes and modified by PPAR gamma activation include TNF alpha and leptin, which both interfere with glucose homeostasis. In addition to its effects on these proteins, PPAR gamma also profoundly affects fatty acid metabolism. Activation of PPAR gamma will selectively induce the expression of several genes involved in fatty acid uptake, such as lipoprotein lipase, fatty acid transport protein and acyl-CoA synthetase, in adipose tissue without changing their expression in muscle tissue. This co-ordinate regulation of fatty acid partitioning by PPAR gamma results in an adipocyte 'FFA steal' causing a relative depletion of fatty acids in the muscle. Based on the well established interference of muscle fatty acid and glucose metabolism it is hypothesized that reversal of muscle fatty acid accumulation will contribute to the improvement in whole body glucose homeostasis. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.