Long-chain fatty acids decrease lipoprotein lipase activity of cultured rat adipocyte precursors

The effect of fatty acids on rat adipocyte precursor lipoprotein lipase (LPL) activity was examined. Cellular LPL activity in cultured perirenal precursors reached a maximum after 6 days. At day 6, addition of 10^-8 mol/L oleic acid to the culture medium for 6 hours resulted in a significant reduction of LPL activity. Exposing cultured precursors to 10^-4 mol/L oleic acid caused more than a 50% decrease of intracellular LPL activity measured in either acetone-ether or detergent extracts and more than a 60% decrease of heparin-releasable LPL activity. These reductions were evident within 2.5 hours of exposure to oleic acid, and exposure to oleic acid for as little as 15 minutes caused a subsequent decrease in LPL activity. LPL activity recovered 48 hours after removal of oleic acid from culture medium. Decreased LPL activity after oleic acid exposure was also noted in epididymal cells and in differentiated adipocyte precursors. The extent of decrease of LPL activity upon fatty acid exposure was dependent on the presence of the carboxyl group and was affected by acyl chain length. Although oleic acid did not affect protein synthesis estimated by [³H]-leucine incorporation, LPL mRNA levels were decreased following exposure of cells to oleic acid. Glycerol-3-phosphate dehydrogenase (G3PD) activity and mRNA levels were not affected by oleic acid exposure. Hence, fatty acids cause a dose-, acyl chain-, and carboxyl group-dependent specific decrease of heparin-releasable and intracellular LPL activities in cultured rat adipocyte precursors; this effect is associated with and is likely caused at least in part by a decrease in LPL mRNA levels.