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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 Feb;81(2):300–309. doi: 10.1172/JCI113321

Interaction of dietary cholesterol and triglycerides in the regulation of hepatic low density lipoprotein transport in the hamster.

D K Spady 1, J M Dietschy 1
PMCID: PMC329571  PMID: 2448340

Abstract

These studies report the effects of dietary cholesterol and triglyceride on rates of receptor-dependent and receptor-independent LDL transport in the liver of the hamster. In animals fed diets enriched with 0.1, 0.25, or 1% cholesterol for 1 mo, receptor-dependent LDL transport in the liver was suppressed by 43, 63, and 77%, respectively, and there were reciprocal changes in plasma LDL-cholesterol concentrations. In addition, dietary triglycerides modified the effect of dietary cholesterol on hepatic LDL transport and plasma LDL concentrations so that at each level of cholesterol intake, polyunsaturated triglycerides diminished and saturated triglycerides accentuated the effect of dietary cholesterol. When animals were raised from weaning on diets containing small amounts of cholesterol, the decline in receptor-dependent LDL transport was nearly abolished by the addition of polyunsaturated or monounsaturated triglycerides, but was markedly augmented by the addition of saturated lipids. When animals raised on diets containing cholesterol and saturated triglycerides were returned to the low cholesterol, low triglyceride control diet, hepatic receptor-dependent LDL transport and plasma LDL-cholesterol concentrations returned essentially to normal within 2 wk. Neither receptor-independent LDL transport nor the receptor-dependent uptake of asialofetuin was significantly altered by dietary cholesterol or triglyceride suggesting that the effect of these lipids on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physiochemical properties of hepatic membranes. These studies demonstrate the important role of saturated triglycerides in augmenting the effect of cholesterol in suppressing hepatic LDL receptor activity and elevating LDL-cholesterol levels.

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Selected References

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  1. AHRENS E. H., Jr, INSULL W., Jr, BLOMSTRAND R., HIRSCH J., TSALTAS T. T., PETERSON M. L. The influence of dietary fats on serum-lipid levels in man. Lancet. 1957 May 11;272(6976):943–953. doi: 10.1016/s0140-6736(57)91280-1. [DOI] [PubMed] [Google Scholar]
  2. Andersen J. M., Dietschy J. M. Relative importance of high and low density lipoproteins in the regulation of cholesterol synthesis in the adrenal gland, ovary, and testis of the rat. J Biol Chem. 1978 Dec 25;253(24):9024–9032. [PubMed] [Google Scholar]
  3. BEVERIDGE J. M., CONNELL W. F., MAYER G. A. Dietary factors affecting the level of plasma cholesterol in humans: the role of fat. Can J Biochem Physiol. 1956 May;34(3):441–455. [PubMed] [Google Scholar]
  4. BRONTE-STEWART B., ANTONIS A., EALES L., BROCK J. F. Effects of feeding different fats on serum-cholesterol level. Lancet. 1956 Apr 28;270(6922):521–526. doi: 10.1016/s0140-6736(56)90592-x. [DOI] [PubMed] [Google Scholar]
  5. Becker N., Illingworth D. R., Alaupovic P., Connor W. E., Sundberg E. E. Effects of saturated, monounsaturated, and omega-6 polyunsaturated fatty acids on plasma lipids, lipoproteins, and apoproteins in humans. Am J Clin Nutr. 1983 Mar;37(3):355–360. doi: 10.1093/ajcn/37.3.355. [DOI] [PubMed] [Google Scholar]
  6. Bilheimer D. W., Eisenberg S., Levy R. I. The metabolism of very low density lipoprotein proteins. I. Preliminary in vitro and in vivo observations. Biochim Biophys Acta. 1972 Feb 21;260(2):212–221. doi: 10.1016/0005-2760(72)90034-3. [DOI] [PubMed] [Google Scholar]
  7. Bilheimer D. W., Watanabe Y., Kita T. Impaired receptor-mediated catabolism of low density lipoprotein in the WHHL rabbit, an animal model of familial hypercholesterolemia. Proc Natl Acad Sci U S A. 1982 May;79(10):3305–3309. doi: 10.1073/pnas.79.10.3305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CONNOR W. E., STONE D. B., HODGES R. E. THE INTERRELATED EFFECTS OF DIETARY CHOLESTEROL AND FAT UPON HUMAN SERUM LIPID LEVELS. J Clin Invest. 1964 Aug;43:1691–1696. doi: 10.1172/JCI105044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Connor W. E., Witiak D. T., Stone D. B., Armstrong M. L. Cholesterol balance and fecal neutral steroid and bile acid excretion in normal men fed dietary fats of different fatty acid composition. J Clin Invest. 1969 Aug;48(8):1363–1375. doi: 10.1172/JCI106102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. ERICKSON B. A., COOTS R. H., MATTSON F. H., KLIGMAN A. M. THE EFFECT OF PARTIAL HYDROGENATION OF DIETARY FATS, OF THE RATIO OF POLYUNSATURATED TO SATURATED FATTY ACIDS, AND OF DIETARY CHOLESTEROL UPON PLASMA LIPIDS IN MAN. J Clin Invest. 1964 Nov;43:2017–2025. doi: 10.1172/JCI105076. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Faust J. R., Luskey K. L., Chin D. J., Goldstein J. L., Brown M. S. Regulation of synthesis and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase by low density lipoprotein and 25-hydroxycholesterol in UT-1 cells. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5205–5209. doi: 10.1073/pnas.79.17.5205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Glass C. K., Pittman R. C., Keller G. A., Steinberg D. Tissue sites of degradation of apoprotein A-I in the rat. J Biol Chem. 1983 Jun 10;258(11):7161–7167. [PubMed] [Google Scholar]
  13. Goodnight S. H., Jr, Harris W. S., Connor W. E., Illingworth D. R. Polyunsaturated fatty acids, hyperlipidemia, and thrombosis. Arteriosclerosis. 1982 Mar-Apr;2(2):87–113. doi: 10.1161/01.atv.2.2.87. [DOI] [PubMed] [Google Scholar]
  14. Jeske D. J., Dietschy J. M. Regulation of rates of cholesterol synthesis in vivo in the liver and carcass of the rat measured using [3H]water. J Lipid Res. 1980 Mar;21(3):364–376. [PubMed] [Google Scholar]
  15. KINSELL L. W., PARTRIDGE J., BOLING L., MARGEN S., MICHAELS G. Dietary modification of serum cholesterol and phospholipid levels. J Clin Endocrinol Metab. 1952 Jul;12(7):909–913. doi: 10.1210/jcem-12-7-909. [DOI] [PubMed] [Google Scholar]
  16. Kesaniemi Y. A., Witztum J. L., Steinbrecher U. P. Receptor-mediated catabolism of low density lipoprotein in man. Quantitation using glucosylated low density lipoprotein. J Clin Invest. 1983 Apr;71(4):950–959. doi: 10.1172/JCI110849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lewis B. Plasma-lipoprotein interrelationships. Biochem Soc Trans. 1977;5(2):589–601. doi: 10.1042/bst0050589. [DOI] [PubMed] [Google Scholar]
  18. Luskey K. L., Faust J. R., Chin D. J., Brown M. S., Goldstein J. L. Amplification of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, but not for the 53-kDa protein, in UT-1 cells. J Biol Chem. 1983 Jul 10;258(13):8462–8469. [PubMed] [Google Scholar]
  19. Mahley R. W., Weisgraber K. H., Melchior G. W., Innerarity T. L., Holcombe K. S. Inhibition of receptor-mediated clearance of lysine and arginine-modified lipoproteins from the plasma of rats and monkeys. Proc Natl Acad Sci U S A. 1980 Jan;77(1):225–229. doi: 10.1073/pnas.77.1.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Meddings J. B., Dietschy J. M. Regulation of plasma levels of low-density lipoprotein cholesterol: interpretation of data on low-density lipoprotein turnover in man. Circulation. 1986 Oct;74(4):805–814. doi: 10.1161/01.cir.74.4.805. [DOI] [PubMed] [Google Scholar]
  21. Munford R. S., Andersen J. M., Dietschy J. M. Sites of tissue binding and uptake in vivo of bacterial lipopolysaccharide-high density lipoprotein complexes: studies in the rat and squirrel monkey. J Clin Invest. 1981 Dec;68(6):1503–1513. doi: 10.1172/JCI110404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nervi F. O., Weis H. J., Dietschy J. M. The kinetic characteristics of inhibition of hepatic cholesterogenesis by lipoproteins of intestinal origin. J Biol Chem. 1975 Jun 10;250(11):4145–4151. [PubMed] [Google Scholar]
  23. Pardridge W. M., Van Herle A. J., Naruse R. T., Fierer G., Costin A. In vivo quantification of receptor-mediated uptake of asialoglycoproteins by rat liver. J Biol Chem. 1983 Jan 25;258(2):990–994. [PubMed] [Google Scholar]
  24. Schwartz A. L., Fridovich S. E., Lodish H. F. Kinetics of internalization and recycling of the asialoglycoprotein receptor in a hepatoma cell line. J Biol Chem. 1982 Apr 25;257(8):4230–4237. [PubMed] [Google Scholar]
  25. Shepherd J., Packard C. J., Grundy S. M., Yeshurun D., Gotto A. M., Jr, Taunton O. D. Effects of saturated and polyunsaturated fat diets on the chemical composition and metabolism of low density lipoproteins in man. J Lipid Res. 1980 Jan;21(1):91–99. [PubMed] [Google Scholar]
  26. Spady D. K., Bilheimer D. W., Dietschy J. M. Rates of receptor-dependent and -independent low density lipoprotein uptake in the hamster. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3499–3503. doi: 10.1073/pnas.80.11.3499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Spady D. K., Dietschy J. M. Dietary saturated triacylglycerols suppress hepatic low density lipoprotein receptor activity in the hamster. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4526–4530. doi: 10.1073/pnas.82.13.4526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Spady D. K., Dietschy J. M. Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat. J Lipid Res. 1983 Mar;24(3):303–315. [PubMed] [Google Scholar]
  29. Spady D. K., Huettinger M., Bilheimer D. W., Dietschy J. M. Role of receptor-independent low density lipoprotein transport in the maintenance of tissue cholesterol balance in the normal and WHHL rabbit. J Lipid Res. 1987 Jan;28(1):32–41. [PubMed] [Google Scholar]
  30. Spady D. K., Meddings J. B., Dietschy J. M. Kinetic constants for receptor-dependent and receptor-independent low density lipoprotein transport in the tissues of the rat and hamster. J Clin Invest. 1986 May;77(5):1474–1481. doi: 10.1172/JCI112460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spady D. K., Stange E. F., Bilhartz L. E., Dietschy J. M. Bile acids regulate hepatic low density lipoprotein receptor activity in the hamster by altering cholesterol flux across the liver. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1916–1920. doi: 10.1073/pnas.83.6.1916. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Spady D. K., Turley S. D., Dietschy J. M. Rates of low density lipoprotein uptake and cholesterol synthesis are regulated independently in the liver. J Lipid Res. 1985 Apr;26(4):465–472. [PubMed] [Google Scholar]
  33. Spady D. K., Turley S. D., Dietschy J. M. Receptor-independent low density lipoprotein transport in the rat in vivo. Quantitation, characterization, and metabolic consequences. J Clin Invest. 1985 Sep;76(3):1113–1122. doi: 10.1172/JCI112066. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Turner J. D., Le N. A., Brown W. V. Effect of changing dietary fat saturation on low-density lipoprotein metabolism in man. Am J Physiol. 1981 Jul;241(1):E57–E63. doi: 10.1152/ajpendo.1981.241.1.E57. [DOI] [PubMed] [Google Scholar]

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