FATTY-ACIDS REGULATE THE EXPRESSION OF LIPOPROTEIN-LIPASE GENE AND ACTIVITY IN PREADIPOSE AND ADIPOSE-CELLS

During fasting, a reduction in lipoprotein lipase (LPL) activity has b een observed in rat fat pad with no change in enzyme mass, whereas LPL mRNA and synthesis are increased, suggesting that insulin and/or fatt y acids (FA) regulate LPL activity post-translationaly [Doolittle, Ben -Zeev, Elovson, Martin and Kirch-gessner (1990) J. Biol. Chem. 265, 45 70-4577]. To examine the role of FA, either preadipose Ob1771 cells or Ob1771 and 3T3-F442A adipose cells were exposed to long-chain FA and to 2-bromopalmitate, a non-metabolized FA. A rapid (2-8 h) and dose-de pendent increase (up to 6-fold) in LPL mRNA occurred, primarily due to increased transcription, which is accompanied by a decrease (down to 4-fold) in LPL cellular activity. Under these conditions, secretion of active LPL was nearly abolished. Removal of FA led to full recovery o f LPL activity, LPL gene expression in 3T3-C2 fibroblasts was not affe cted by FA treatment, However fatty acid-activated receptor transfecte d-3T3-C2 cells, which show FA responsiveness, had increased LPL gene e xpression upon FA addition. LPL synthesis and cellular content appeare d unaffected by FA treatment, whereas secretion of LPL was inhibited. These results indicate that FA regulate the posttranslational processi ng of LPL. It is proposed that the regulation of LPL activity by FA is important with regard to the fine-tuning of FA entry into adipocytes during fasting/feeding periods.