Advertisement

Klinische Wochenschrift

, Volume 62, Issue 8, pp 338–345 | Cite as

Regulation of cholesterol metabolism in man and in other species

  • J. M. Dietschy
Heinrich-Wieland-Preis-Vorlesung

Summary

In the whole animal and in man, cholesterol is acquired either by absorption from the diet or by synthesis in the various organs. While there are marked variations among different animal species, the liver and intestine are generally the most important organs for the synthesis of cholesterol, although recent data indicate that nearly all of the remaining tissues of the body also are capable of significant cholesterol synthesis. Peripheral tissues also acquire cholesterol through the uptake of low density lipoproteins (LDL). However, most LDL are removed from the plasma by the liver, and more than 90|X% of this clearance process is mediated by the LDL receptor. Hence, the circulating levels of cholesterol carried in LDL are determined primarily by the rate of LDL production and the rate of LDL uptake by the liver. Changes in the rate of entry of cholesterol into the body are compensated for primarily by changes in the rate of cholesterol synthesis in the liver and, to some extent, in the intestine. As long as these changes in synthetic rates can fully compensate for the variations in the rate of cholesterol entry into or exit from the body, the rate of LDL uptake by the liver and the intestine, and the circulating levels of plasma cholesterol, remain essentially constant. When the adaptive changes in cholesterol synthesis are not adequate to meet the changes in cholesterol entry or exit, then the level of LDL receptor activity in the liver may either increase or decrease, resulting in a corresponding lowering or elevation of the circulating plasma LDL-cholesterol levels.

Key words

Cholesterol synthesis Low density lipoproteins 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Turley SD, Dietschy JM (1982) Cholesterol metabolism and excretion. In: Arias I, Popper H, Schachter D, Shafritz DA (eds) The liver: biology and pathobiology. Raven Press, New York, pp 467–492Google Scholar
  2. 2.
    Westergaard H, Dietschy JM (1976) The mechanism whereby bile acid micelles increase the rate of fatty acid and cholesterol uptake into the intestinal mucosal cell. J Clin Invest 58:97–108Google Scholar
  3. 3.
    Thomson ABR, Dietschy JM (1981) Intestinal lipid absorption: Major extracellular and intracellular events. In: Johnson LR (ed) Physiology of the gastrointestinal tract. Raven Press, New York, pp 1147–1220Google Scholar
  4. 4.
    Fielding CJ (1978) Origin and properties of remnant lipoproteins. In: Dietschy JM, Gotto AM Jr, Ontko JA (eds) Disturbances in lipid and lipoprotein metabolism. Waverly Press, Baltimore, pp 83–98Google Scholar
  5. 5.
    Sherrill BD, Dietschy JM (1978) Characterization of the sinusoidal transport process responsible for uptake of chylomicrons by the liver. J Biol Chem 253:1859–1867Google Scholar
  6. 6.
    Nervi FO, Weis HJ, Dietschy JM (1975) The kinetic characteristics of inhibition of hepatic cholesterogenesis by lipoproteins of intestinal origin. J Biol Chem 250:4145–4151Google Scholar
  7. 7.
    Nervi FO, Dietschy JM (1975) Ability of six different lipoprotein fractions to regulate the rate of hepatic cholesterogenesis in vivo. J Biol Chem 250:8704–9711Google Scholar
  8. 8.
    Havel RJ (1982) Approach to the patient with hyperlipidemia. In: Havel RJ (ed) The medical clinics of North America. Saunders, Philadelphia, pp 319–333Google Scholar
  9. 9.
    Andersen JM, Dietschy JM (1976) Cholesterogenesis: Derepression in extrahepatic tissue with 4-aminopyrazola[3,4-d]pyrimidine. Science 193:903–905Google Scholar
  10. 10.
    Andersen JM, Dietschy JM (1977) Regulation of sterol synthesis in 15 tissues of rat II. Role of rat and human high and low density plasma lipoproteins and of rat chylomicron remnants. J Biol Chem 252:3652–3659Google Scholar
  11. 11.
    Mahley RW (1983) Apolipoprotein E and cholesterol metabolism. Klin Wochenschr 61:225–232Google Scholar
  12. 12.
    Andersen JM, Dietschy JM (1979) Absolute rates of cholesterol synthesis in extrahepatic tissues measured with3H-labeled water and14C-labeled substrates. J Lipid Res 20:740–752Google Scholar
  13. 13.
    Dietschy JM, McGarry JD (1974) Limitations of acetate as a substrate for measuring cholesterol synthesis in liver. J Biol Chem 249:52–58Google Scholar
  14. 14.
    Dietschy JM, Brown MS (1974) Effect of alterations of the specific activity of the intracellular acetyl CoA pool on apparent rates of hepatic cholesterogenesis. J Lipid Res 15:508–516Google Scholar
  15. 15.
    Brown MS, Goldstein JL, Dietschy JD (1979) Active and inactive forms of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the liver of the rat. J Biol Chem 254:5144–5149Google Scholar
  16. 16.
    Dietschy JM, Wilson JD (1970) Regulation of cholesterol metabolism. New Engl J Med :1128–1249Google Scholar
  17. 17.
    Jeske DJ, Dietschy JM (1980) Regulation of rates of cholesterol synthesis in vivo in the liver and carcass of the rat measured using [3H]water. J Lipid Res 21:364–376Google Scholar
  18. 18.
    Turley SD, Andersen JM, Dietschy JM (1981) Rates of sterol synthesis and uptake in the major organs of the rat in vivo. J Lipid Res 22:551–569Google Scholar
  19. 19.
    Spady DK, Dietschy JM (1983) Sterol synthesis in vivo in 18 tissues of the squirrel monkey, guinea pig, rabbit, hamster, and rat. J Lipid Res 24:303–315Google Scholar
  20. 20.
    Spady DK, Bilheimer DW, Dietschy JM (1983) Rates of receptor-dependent and -independent low density lipoprotein uptake in the hamster. Proc Natl Acad Sci USA 80:3499–3503Google Scholar
  21. 21.
    Dietschy JM, Turley SD, Spady DK (1983) The role of the liver in lipid and lipoprotein metabolism. In: Bianchi L, Gerok W, Landmann L, Sickinger K, Stalder GA (eds) Liver in metabolic diseases. MTP Press, Boston The Hague Dordrecht Lancaster, pp 25–39Google Scholar
  22. 22.
    Pittman RC, Attie AD, Carew TE, Steinberg D (1979) Tissue sites of degradation of low density lipoprotein: Application of a method for determining the fate of plasma proteins. Proc Natl Acad Sci USA 76:5345–5349Google Scholar
  23. 23.
    Andersen JM, Dietschy JM (1981) Kinetic parameters of the lipoprotein transport systems in the adrenal gland of the rat determined in vivo. Comparison of low and high density lipoproteins of human and rat origin. J Biol Chem 256:7362–7370Google Scholar
  24. 24.
    Brown MS, Goldstein JL (1975) Lipoprotein receptors and the genetic control of cholesterol metabolism in cultured human cells. Naturwissenschaften 62:385–389Google Scholar
  25. 25.
    Mahley RW, Weisgraber KH, Melchior GW, Innerarity TL, Holcombe KS (1980) Inhibition of receptor-mediated clearance of lysine and arginine-modified lipoproteins from the plasma of lysine and arginine-modified lipoproteins from the plasma of rats and monkeys. Proc Natl Acad Sci USA 77:225–229Google Scholar
  26. 26.
    Brown MS, Goldstein JL (1983) Lipoprotein receptors in the liver: Control signals for plasma cholesterol traffic. J Clin Invest 72:743–747Google Scholar
  27. 27.
    Stange EF, Dietschy JM (1983) Cholesterol synthesis and low density lipoprotein uptake are regulated independently in rat small intestinal epithelium. Proc Natl Acad Sci USA 80:5739–5743Google Scholar

Copyright information

© Springer-Verlag 1984

Authors and Affiliations

  • J. M. Dietschy
    • 1
  1. 1.Department of Internal MedicineThe University of Texas Health Science Center at Dallas, Southwestern Medical SchoolDallasUSA

Personalised recommendations