Lipoprotein lipase synthesis and secretion: effects of concentration and type of fatty acids in adipocyte cell culture1

Fatty acids (FA) were added to differentiating chick adipocytes to study their effects on the synthesis and secretion of avian lipoprotein lipase (LPL). Oleate (18:ln-9), eicosapentaenoate (EPA, 20:5n-3), and linoleate (18:2n-6) were complexed to fatty acid-free bovine serum albumin (BSA) and separately added to cells in RMPI-1640 media containing 0.5% delipidated hen serum. LPL secretion in the presence of 10 U/ml heparin was used as a means of estimating LPL synthesis. FA from 50 pM to 165 pM depressed LPL secretion for cells exposed to 20:5n-3 and 18:2n-6. The decrease in adipocyte LPL secretion was only observed with chronic administration of FA. In other experiments, the rate of LPL synthesis was estimated by incorporation of radiolabel (Tran 35S-labelTM) in cells exposed to 50 pM FA. Total radioactivity incorporated into LPL, expressed as a percentage of total trichloroacetic acid (TCA)precipitable radioactivity, was not affected in cells fed 18:ln-9 but was significantly decreased for cells fed 20:5n-3 (45%) or 18:2n-6 (67%) relative to controls given equimolar BSA (33 pM). Abundance of LPL message in similarly treated cells also decreased for cells incubated with 20:5n-3 or 18:2n-6 (35%) relative to controls and 18:ln-9-treated cells. A decrease in adipocyte LPL secretion was also observed with administration of lipoprotein (d < 1.006 g/ml) enriched in n-3 and n-6 fatty acids. LPL secretion of cells incubated with n-3 enriched lipoprotein at 50 pM and 75 pM triglyceride fatty acid equivalents was significantly greater than that of cells incubated with n-6-enriched lipoprotein. Interestingly, at the same concentrations of triglyceride fatty acids, lipoproteins enriched with n-9 fatty acids had no effect on LPL secretion relative to controls. These studies document that in cultured avian adipocytes, LPL secretion, synthesis, and level of message are decreased by chronic administration of n-3 and n-6 fatty acids. In contrast, in adipocytes supplemented with oleic acid there was no effect on LPL synthesis and secretion.-Montalto, M. B., and A. Bensadoun. Lipoprotein lipase synthesis and secretion: effects of concentration and type of fatty acids in adipocyte cell culture. J. Lipid Res. 1993. 34: 397-407. Supplementary key words free fatty acids eicosapentaenoic acid linoleic acid LPL mRNA oleic acid polyunsaturated fatty acid Lipoprotein lipase (LPL) is primarily synthesized and secreted by subendothelial cells of adipose, heart, and skeletal muscle (1, 2) and is responsible for the hydrolysis of the triglyceride-rich core of circulating chylomicrons and very low density lipoproteins (1-7). Control of LPL gene expression by hormonal factors has been shown to be tissue-specific (5, 7). Insulin increases gene expression in adipocytes (8-11). In heart cells CAMP increases cellular LPL dramatically (12); in adipocytes the effect of CAMP is more complex. Short term exposure to CAMP decreases LPL synthesis and secretion (12, 13) whereas long term treatment (24 h) increases the secretion of the lipase. Epidemiological and clinical research has suggested that a diet rich in polyunsaturated fatty acids may decrease the incidence of cardiovascular disease by lowering plasma triglyceride and very low density lipoprotein concentrations (14, 15). Long chain fatty acids derived from fish oil, mainly eicosapentaenoic acid (EPA, 20:5n-3), have been shown to be an important factor in the hypotriglyceridemic response to diets containing fish oil (14, 16). It is possible that fatty acids in fish oils and other oils affect the synthesis and secretion of LPL; changes in LPL activity would influence the clearance of