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. 1995 Jun 1;308(Pt 2):537–542. doi: 10.1042/bj3080537

Quantification in vivo of the effects of different types of dietary fat on the loci of control involved in hepatic triacylglycerol secretion.

A M Moir 1, B S Park 1, V A Zammit 1
PMCID: PMC1136958  PMID: 7772038

Abstract

Polyunsaturated fatty acids (PUFA) have been suggested to exert their hypotriglyceridaemic effect through several possible mechanisms that would be expected to decrease the rate of hepatic very-low-density-lipoprotein-triacylglycerol secretion. We have quantified the role played in vivo by changes in the pattern of partitioning of (i) acyl-CoA between oxidation and esterification, (ii) diacylglycerol between synthesis of triacylglycerol and of the major phospholipids, and (iii) triacylglycerol between secretion and storage within the liver, in response to two dietary levels of n-6 and n-3 PUFA. In order to achieve this we used the technique of selective labelling of hepatic fatty acids in vivo. Compared with a predominantly saturated fatty acid diet, both n-6 and n-3 PUFA intake resulted in a decrease in the proportion of acyl moieties that were secreted by the liver, through an increased diversion of acyl-CoA towards oxidation and a lower fractional rate of secretion of newly synthesized triacylglycerol. In addition, a diet rich in n-3 fatty acids resulted not only in a greater magnitude of these effects but also in a doubling of the partitioning of diacylglycerol towards phospholipid labelling. It is shown that the overall 50% reduction achieved by fish oil feeding in the proportion of acyl groups that were secreted by the liver was distributed over all three branch points. The contribution of each of these adaptations was quantified. The application of such an approach, i.e. the localization and in vivo quantification of the importance of loci of control, in studies on dietary and pharmacological agents that affect lipaemia, is discussed.

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Selected References

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  1. Aarsland A., Lundquist M., Børretsen B., Berge R. K. On the effect of peroxisomal beta-oxidation and carnitine palmitoyltransferase activity by eicosapentaenoic acid in liver and heart from rats. Lipids. 1990 Sep;25(9):546–548. doi: 10.1007/BF02537162. [DOI] [PubMed] [Google Scholar]
  2. BARTLETT G. R. Colorimetric assay methods for free and phosphorylated glyceric acids. J Biol Chem. 1959 Mar;234(3):469–471. [PubMed] [Google Scholar]
  3. Baltzell J. K., Jenkins R. L., Wooten J. T., Otto D. A. Dependence of the plasma triacylglycerol-lowering effect of fish oil on insulin replacement in streptozotocin diabetic rats. Biochim Biophys Acta. 1993 Apr 7;1167(2):197–203. doi: 10.1016/0005-2760(93)90162-3. [DOI] [PubMed] [Google Scholar]
  4. Berge R. K., Nilsson A., Husøy A. M. Rapid stimulation of liver palmitoyl-CoA synthetase, carnitine palmitoyltransferase and glycerophosphate acyltransferase compared to peroxisomal beta-oxidation and palmitoyl-CoA hydrolase in rats fed high-fat diets. Biochim Biophys Acta. 1988 Jun 15;960(3):417–426. doi: 10.1016/0005-2760(88)90050-1. [DOI] [PubMed] [Google Scholar]
  5. Bergseth S., Christiansen E. N., Bremer J. The effect of feeding fish oils, vegetable oils and clofibrate on the ketogenesis from long chain fatty acids in hepatocytes. Lipids. 1986 Aug;21(8):508–514. doi: 10.1007/BF02535638. [DOI] [PubMed] [Google Scholar]
  6. Byrne C. D., Wang T. W., Hales C. N. Control of Hep G2-cell triacylglycerol and apolipoprotein B synthesis and secretion by polyunsaturated non-esterified fatty acids and insulin. Biochem J. 1992 Nov 15;288(Pt 1):101–107. doi: 10.1042/bj2880101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Clarke S. D., Jump D. B. Dietary polyunsaturated fatty acid regulation of gene transcription. Annu Rev Nutr. 1994;14:83–98. doi: 10.1146/annurev.nu.14.070194.000503. [DOI] [PubMed] [Google Scholar]
  8. Coleman R., Bell R. M. Triacylglycerol synthesis in isolated fat cells. Studies on the microsomal diacylglycerol acyltransferase activity using ethanol-dispersed diacylglycerols. J Biol Chem. 1976 Aug 10;251(15):4537–4543. [PubMed] [Google Scholar]
  9. Coniglio J. G. How does fish oil lower plasma triglycerides? Nutr Rev. 1992 Jul;50(7):195–197. doi: 10.1111/j.1753-4887.1992.tb01324.x. [DOI] [PubMed] [Google Scholar]
  10. Duerden J. M., Marsh B., Burnham F. J., Gibbons G. F. Regulation of hepatic synthesis and secretion of cholesterol and glycerolipids in animals maintained in different nutritional states. Biochem J. 1990 Nov 1;271(3):761–766. doi: 10.1042/bj2710761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Emmison N., Zammit V. A., Agius L. Triacylglycerol accumulation and secretion in hepatocyte cultures. Effects of insulin, albumin and Triton WR 1339. Biochem J. 1992 Jul 15;285(Pt 2):655–660. doi: 10.1042/bj2850655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Halminski M. A., Marsh J. B., Harrison E. H. Differential effects of fish oil, safflower oil and palm oil on fatty acid oxidation and glycerolipid synthesis in rat liver. J Nutr. 1991 Oct;121(10):1554–1561. doi: 10.1093/jn/121.10.1554. [DOI] [PubMed] [Google Scholar]
  13. Lawson N., Jennings R. J., Pollard A. D., Sturton R. G., Ralph S. J., Marsden C. A., Fears R., Brindley D. N. Effects of chronic modification of dietary fat and carbohydrate in rats. Biochem J. 1981 Nov 15;200(2):265–273. doi: 10.1042/bj2000265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Levy E., Roy C. C., Goldstein R., Bar-On H., Ziv E. Metabolic fate of chylomicrons obtained from rats maintained on diets varying in fatty acid composition. J Am Coll Nutr. 1991 Feb;10(1):69–78. doi: 10.1080/07315724.1991.10718129. [DOI] [PubMed] [Google Scholar]
  15. Lottenberg A. M., Oliveira H. C., Nakandakare E. R., Quintão E. C. Effect of dietary fish oil on the rate of very low density lipoprotein triacylglycerol formation and on the metabolism of chylomicrons. Lipids. 1992 May;27(5):326–330. doi: 10.1007/BF02536145. [DOI] [PubMed] [Google Scholar]
  16. Marsh J. B., Topping D. L., Nestel P. J. Comparative effects of dietary fish oil and carbohydrate on plasma lipids and hepatic activities of phosphatidate phosphohydrolase, diacylglycerol acyltransferase and neutral lipase activities in the rat. Biochim Biophys Acta. 1987 Nov 21;922(2):239–243. doi: 10.1016/0005-2760(87)90160-3. [DOI] [PubMed] [Google Scholar]
  17. Moir A. M., Zammit V. A. Monitoring of changes in hepatic fatty acid and glycerolipid metabolism during the starved-to-fed transition in vivo. Studies on awake, unrestrained rats. Biochem J. 1993 Jan 1;289(Pt 1):49–55. doi: 10.1042/bj2890049. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moir A. M., Zammit V. A. Rapid switch of hepatic fatty acid metabolism from oxidation to esterification during diurnal feeding of meal-fed rats correlates with changes in the properties of acetyl-CoA carboxylase, but not of carnitine palmitoyltransferase I. Biochem J. 1993 Apr 1;291(Pt 1):241–246. doi: 10.1042/bj2910241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Otto D. A., Baltzell J. K., Wooten J. T. Reduction in triacylglycerol levels by fish oil correlates with free fatty acid levels in ad libitum fed rats. Lipids. 1992 Dec;27(12):1013–1017. doi: 10.1007/BF02535581. [DOI] [PubMed] [Google Scholar]
  20. Otto D. A., Tsai C. E., Baltzell J. K., Wooten J. T. Apparent inhibition of hepatic triacylglycerol secretion, independent of synthesis, in high-fat fish oil-fed rats: role for insulin. Biochim Biophys Acta. 1991 Feb 26;1082(1):37–48. doi: 10.1016/0005-2760(91)90297-u. [DOI] [PubMed] [Google Scholar]
  21. Ribeiro A., Mangeney M., Cardot P., Loriette C., Rayssiguier Y., Chambaz J., Bereziat G. Effect of dietary fish oil and corn oil on lipid metabolism and apolipoprotein gene expression by rat liver. Eur J Biochem. 1991 Mar 14;196(2):499–507. doi: 10.1111/j.1432-1033.1991.tb15842.x. [DOI] [PubMed] [Google Scholar]
  22. Rustan A. C., Christiansen E. N., Drevon C. A. Serum lipids, hepatic glycerolipid metabolism and peroxisomal fatty acid oxidation in rats fed omega-3 and omega-6 fatty acids. Biochem J. 1992 Apr 15;283(Pt 2):333–339. doi: 10.1042/bj2830333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Rustan A. C., Nossen J. O., Christiansen E. N., Drevon C. A. Eicosapentaenoic acid reduces hepatic synthesis and secretion of triacylglycerol by decreasing the activity of acyl-coenzyme A:1,2-diacylglycerol acyltransferase. J Lipid Res. 1988 Nov;29(11):1417–1426. [PubMed] [Google Scholar]
  24. Sanders T. A., Vickers M., Haines A. P. Effect on blood lipids and haemostasis of a supplement of cod-liver oil, rich in eicosapentaenoic and docosahexaenoic acids, in healthy young men. Clin Sci (Lond) 1981 Sep;61(3):317–324. doi: 10.1042/cs0610317. [DOI] [PubMed] [Google Scholar]
  25. Surette M. E., Whelan J., Broughton K. S., Kinsella J. E. Evidence for mechanisms of the hypotriglyceridemic effect of n-3 polyunsaturated fatty acids. Biochim Biophys Acta. 1992 Jun 22;1126(2):199–205. doi: 10.1016/0005-2760(92)90291-3. [DOI] [PubMed] [Google Scholar]
  26. Tijburg L. B., Geelen M. J., van Golde L. M. Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine in the liver. Biochim Biophys Acta. 1989 Jul 17;1004(1):1–19. doi: 10.1016/0005-2760(89)90206-3. [DOI] [PubMed] [Google Scholar]
  27. Ventura M. A., Woollett L. A., Spady D. K. Dietary fish oil stimulates hepatic low density lipoprotein transport in the rat. J Clin Invest. 1989 Aug;84(2):528–537. doi: 10.1172/JCI114195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Wang H., Chen X., Fisher E. A. N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes. J Clin Invest. 1993 Apr;91(4):1380–1389. doi: 10.1172/JCI116340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Willumsen N., Hexeberg S., Skorve J., Lundquist M., Berge R. K. Docosahexaenoic acid shows no triglyceride-lowering effects but increases the peroxisomal fatty acid oxidation in liver of rats. J Lipid Res. 1993 Jan;34(1):13–22. [PubMed] [Google Scholar]
  30. Willumsen N., Skorve J., Hexeberg S., Rustan A. C., Berge R. K. The hypotriglyceridemic effect of eicosapentaenoic acid in rats is reflected in increased mitochondrial fatty acid oxidation followed by diminished lipogenesis. Lipids. 1993 Aug;28(8):683–690. doi: 10.1007/BF02535987. [DOI] [PubMed] [Google Scholar]
  31. Wilson M. D., Blake W. L., Salati L. M., Clarke S. D. Potency of polyunsaturated and saturated fats as short-term inhibitors of hepatic lipogenesis in rats. J Nutr. 1990 Jun;120(6):544–552. doi: 10.1093/jn/120.6.544. [DOI] [PubMed] [Google Scholar]
  32. Wong S. H., Marsh J. B. Inhibition of apolipoprotein secretion and phosphatidate phosphohydrolase activity by eicosapentaenoic and docosahexaenoic acids in the perfused rat liver. Metabolism. 1988 Dec;37(12):1177–1181. doi: 10.1016/0026-0495(88)90197-7. [DOI] [PubMed] [Google Scholar]
  33. Wong S. H., Nestel P. J., Trimble R. P., Storer G. B., Illman R. J., Topping D. L. The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver. Biochim Biophys Acta. 1984 Feb 9;792(2):103–109. doi: 10.1016/0005-2760(84)90209-1. [DOI] [PubMed] [Google Scholar]
  34. Yamazaki R. K., Shen T., Schade G. B. A diet rich in (n-3) fatty acids increases peroxisomal beta-oxidation activity and lowers plasma triacylglycerols without inhibiting glutathione-dependent detoxication activities in the rat liver. Biochim Biophys Acta. 1987 Jul 13;920(1):62–67. doi: 10.1016/0005-2760(87)90311-0. [DOI] [PubMed] [Google Scholar]
  35. Yeo Y. K., Holub B. J. Influence of dietary fish oil on the relative synthesis of triacylglycerol and phospholipids in rat liver in vivo. Lipids. 1990 Dec;25(12):811–814. doi: 10.1007/BF02535902. [DOI] [PubMed] [Google Scholar]
  36. Zammit V. A., Moir A. M. Monitoring the partitioning of hepatic fatty acids in vivo: keeping track of control. Trends Biochem Sci. 1994 Aug;19(8):313–317. doi: 10.1016/0968-0004(94)90068-x. [DOI] [PubMed] [Google Scholar]
  37. Zhang Z. J., Wilcox H. G., Castellani L., Fungwe T. V., Elam M. B., Heimberg M. Concentration-dependent effects of eicosapentaenoic acid on very low density lipoprotein secretion by the isolated perfused rat liver. Lipids. 1993 May;28(5):419–425. doi: 10.1007/BF02535940. [DOI] [PubMed] [Google Scholar]
  38. Zhang Z. J., Wilcox H. G., Elam M. B., Castellani L. W., Heimberg M. Metabolism of n-3 polyunsaturated fatty acids by the isolated perfused rat liver. Lipids. 1991 Jul;26(7):504–511. doi: 10.1007/BF02536594. [DOI] [PubMed] [Google Scholar]

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