Expression of the adipocyte fatty acid-binding protein in streptozotocin-diabetes: effects of insulin deficiency and supplementation.
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 beta-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Melki
S A
SA
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232.
Abumrad
N A
NA
D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism*; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000097:blood / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D015151:Immunoblotting; D007328:Insulin / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology*; D008297:Male; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012313:RNA / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000235:genetics
D001786:Blood Glucose; D002352:Carrier Proteins; C490174:Fabp7 protein, rat; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D007328:Insulin; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012313:RNA