Advertisement

Hypotriglyceridemic Drugs and Lipoprotein Catabolism

  • S. Eisenberg
Conference paper
Part of the Proceedings in Life Sciences book series (LIFE SCIENCES)

Abstract

In the last DALM Symposium, we described in detail our findings of abnormal lipoprotein systems in human subjects with dyslipoproteinemia, predominantly hypertriglyceridemia (HTG) (1). These studies, recently published (2,3), can be summarized as follows: HTG states are associated with excessive lipid transfer reactions (4). The lipids that are transferred are the hydrophobic cholesteryl ester (CE) and triglyceride (TG) molecules. The reaction thus causes excessive enrichment of VLDL with CE (5,6), while both LDL and HDL lose CE and acquire TG (1,2,7). Since acquired TG in LDL and HDL are hydrolyzed by plasma lipases (8,9), the particles become smaller and denser as compared to the normal lipoproteins. On the basis of these observations; we suggested abnormal metabolism of HTG-lipoproteins (1). For VLDL, we showed that the large and less dense populations, VLDL-I and VLDL-II, contain 50–150% more CE molecules than present in LDL, and pointed out that such particles cannot complete the VLDL → LDL conversion cascade. Hence, in HTG, “remnants” of these VLDL populations must be cleared from the plasma independently of the LDL pathway (1,5). HTG-LDL is CE-poor, TG-rich, small and dense lipoprotein, and the cholesterol content of the LDL decreases with a curvilinear relation to plasma TG levels. Such LDLs, therefore, are expected to be inefficient regulators of cellular metabolic activities that depend on cholesterol influx, e.g., cholesterol synthesis and B,E receptor protein activity. These postulates have been further investigated in our laboratory during the last 3 years, using LDL and cultured human skin fibroblasts.

Keywords

Cholesteryl Ester Human Skin Fibroblast Cellular Metabolic Activity Plasma Lipase Inefficient Regulator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Eisenberg S (1985) Hypertriglyceridemia and atherosclerosis: analysis of an abnormal lipoprotein system and potential beneficial effects of triglyceride lowering therapy. Adv Exp Med Biol 183:73–84PubMedGoogle Scholar
  2. 2.
    Eisenberg S, Gavish D, Oschry Y, Fainaru M, Deckelbaum RJ (1984) Abnormalities in very low, low and high density lipoproteins in hypertriglyceridemia. Reversal towards normal with Bezafibrate treatment. J Clin Invest 74:470–482PubMedCrossRefGoogle Scholar
  3. 3.
    Gavish D, Oschry Y, Fainaru M, Eisenberg S (1986) Change in very low-, low-, and high-density lipoproteins during lipid lowering (Bezafibrate) therapy: studies in type IIA and type IIB hyperlipoproteinemia. Eur J Clin Invest 16:61–68PubMedCrossRefGoogle Scholar
  4. 4.
    Eisenberg S, Deckelbaum R (1986) Intravascular lipoprotein remodelling: neutral lipid transfer proteins. Clin Biochem (in press)Google Scholar
  5. 5.
    Oschry Y, Olivecrona T, Deckelbaum RJ, Eisenberg S (1985) Is hypertriglyceridemic very low density lipoprotein a precursor of normal low density lipoproteins. J Lipid Res 26:158–167PubMedGoogle Scholar
  6. 6.
    Eisenberg S (1985) Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters. J Lipid Res 26:487–494PubMedGoogle Scholar
  7. 7.
    Deckelbaum RJ, Granot E, Oschry Y, Rose L, Eisenberg S (1984) Plasma triglyceride determines structure-composition in low and high density lipoproteins. Arteriosclerosis 4:226–231Google Scholar
  8. 8.
    Deckelbaum R, Eisenberg S, Oschry Y, Olivecrona T (1982) Reverse modification of human plasma low density lipoprotein toward triglyceride rich precursors: a mechanism for losing excess cholesterol ester. J Biol Chem 257:6509–6517PubMedGoogle Scholar
  9. 9.
    Deckelbaum RJ, Eisenberg S, Oschry Y, Granot E, Sharon I, Bengtsson-Olivecrona G (1986) Modelling of human plasma high density lipoproteins: roles of neutral lipid exchange and triglyceride lipases. J Biol Chem 261:5201–5208PubMedGoogle Scholar
  10. 10.
    Kleinman Y, Eisenberg S, Orschry Y, Gavish D, Stein O, Stein Y (1985) Defective metabolism of hypertriglyceridemic low density lipoprotein in cultured human skin fibroblasts. J Clin Invest 75:1796–1803PubMedCrossRefGoogle Scholar
  11. 11.
    Kleinman Y, Schonfeld F, Gavish D, Oschry Y, Eisenberg S (1987) Hypolipidemic therapy modulates expression of apolipoprotein B epitopes on low density lipoproteins. J Lipid Res 28:540–548PubMedGoogle Scholar
  12. 12.
    Kleinman Y, Oschry Y, Berger GMB, Eisenberg S (1986) Familial lipoprotein upase deficiency: abnormal lipoproteins and defective metabolism of low density lipoproteins in cultured human skin fibroblasts (submitted)Google Scholar
  13. 13.
    Kleinman Y, Oschry Y, Eisenberg S (1987) Abnormal regulation of LDL receptor activity and abnormal cellular metabolism of hypertriglyceridemic low density lipoprotein. Normalization with Bezafibrate therapy. Eur J Clin Invest (in press)Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • S. Eisenberg
    • 1
  1. 1.Lipid Research Laboratory, Department of Medicine BHadassah University HospitalJerusalemIsrael

Personalised recommendations