Expression of the adipocyte fatty acid-binding protein in streptozotocin-diabetes: effects

The adipocyte fatty acid-binding protein, aP2 or ALBP, is an abundant cytosolic protein postulated to function in binding and intracellular transport of long-chain fatty acids. In this report, we investigated levels of aP2 mRNA and protein and transcriptional activity of the aP2 gene in tissues from streptozotocin-diabetic rats at different time periods following the induction of diabetes. An average 75% decrease in mRNA for aP2 (relative to mRNA for 8-actin) was observed in all diabetic rats at 7 days post-STZ injection. Insulin supplementation rapidly (2 h) restored aP2 mRNA and the insulin effect was cycloheximide-sensitive. Nuclear transcription assays measured a 60% decrease in transcription of the aP2 gene in diabetic rats that was reversed by insulin administration. Levels of aP2 protein were still high, in some cases, 1 day after the decrease in mRNA levels consistent with a long half-life of the protein. Decreases in aP2 protein were rapidly reversed by insulin administration. There were no changes in aP2 protein in the absence of changes in aP2 mRNA supporting a pretranslational mechanism of regulation. The decrease in aP2 mRNA was delayed in onset when compared with the rapid decline (at day 2 of diabetes) of mRNA for the lipogenic enzyme, fatty acid synthase, and with the accelerated depletion of adipose tissue lipid. Adipose tissue weight and lipid content had decreased by more than 80% 3 days before any significant changes in aP2 expression were observed. Changes in aP2 could not be related to changes in the levels of circulating fatty acids that regulate aP2 expression in vitro. I The study indicated 1) that insulin deficiency and supplementation can regulate expression of aP2 in vivo and 2) that changes in aP2 levels are unlikely to contribute to the abnormalities of fatty acid metabolism in adipose tissue from diabetic rats.-Melki, S. A., and N. A. Abumrad. Expression of the adipocyte fatty acid binding protein with streptozotocin-diabetes: effects of insulin deficiency and supplementation. J. Lipid Res. 1993. 34: 1527-1534. Supplementary key words tein * insulin * streptozotocin diabetes adipose tissue fatty acid-binding proof preadipocytes in culture coinciding with the increase in FA esterification rate (5-7). This induction is dependent on the presence of adipogenesis-promoting hormones, insulin and insulin growth-factor 1, IGF-1 (8, 9). In addition to its postulated roles in intracellular binding and shuttling of FA, there is evidence that aP2 is phosphorylated by the insulin receptor tyrosine kinase leading to the suggestion that it might be involved in the insulinsignaling pathway in adipocytes (10, 11). There is little information concerning regulation of aP2 expression in vivo. Such information is important for evaluating the physiological role of aP2. In particular, the effect of diabetes on aP2 expression would be of interest as this condition is associated with marked disorders of FA metabolism. Diabetes is characterized by an increase in FA mobilization and by a progressive and marked wasting of triglyceride stores in adipose tissue. We examined aP2 expression in streptozotocin (STZ) diabetic rats at different times after induction of diabetes and after insulin supplementation and withdrawal. Metabolic measurements were also carried out under the same conditions. O u r data indicated that levels of aP2 mRNA and protein are markedly decreased by diabetes and this decrease is rapidly reversed by insulin supplementation. However, the decrease in aP2 gene expression was delayed when compared with diabetes-induced alterations in adipose