Abstract
Measurements of transport of triglycerides (TG) in very low density lipoproteins (VLDL) were carried out in 59 patients by injection of radioactive glycerol, determinations of specific activities of VLDL-TG for 48 h thereafter, and treatment of the data by multicompartmental analysis. The patients were divided into three groups: normal weight (89-120% ideal weight), mildly obese (120-135% ideal weight), and markedly obese (135% ideal weight). They had varying levels of VLDL-TG ranging from normal to markedly elevated. In many subjects, there was a positive correlation between concentrations and transport of VLDL indicating that overproduction of VLDL-TG contributed to hypertriglyceridemia. In others, and particularly in several markedly obese subjects, transport rates were greatly increased without significant hypertriglyceridemia, suggesting that they had enhanced capacity to clear TG. In all groups, however, there were patients whose degree of hypertriglyceridemia seemed out of proportion to their transport rates. This finding and the fact that many patients have increased secretion of VLDL-TG without elevated plasma TG suggests that both overproduction of VLDL-TG and insufficient enhancement of clearance contributed to the development of hypertriglyceridemia.
The data showed a poor correlation between transport rates determined by our multicompartment analysis and single-exponential analysis used previously by other investigators (r = 0.46); this comparison was not improved by segregating patients according to their degree of obesity. Although two conversion pathways (fast and slow synthetic paths) were required to fit the data, there was no correlation between transport rates and the ratio of the two pathways. Also, despite the known pathway of conversion of VLDL to low density lipoprotein, no correlation was found between VLDL-TG transport rates and estimated low density lipoprotein-cholesterol concentrations.
Full text
PDFSelected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barter P. J., Nestel P. J. Plasma free fatty acid transport during prolonged glucose consumption and its relationship to plasma triglyceride fatty acids in man. J Lipid Res. 1972 Jul;13(4):483–490. [PubMed] [Google Scholar]
- Berman M., Hall M., 3rd, Levy R. I., Eisenberg S., Bilheimer D. W., Phair R. D., Goebel R. H. Metabolsim of apoB and apoC lipoproteins in man: kinetic studies in normal and hyperlipoproteininemic subjects. J Lipid Res. 1978 Jan;19(1):38–56. [PubMed] [Google Scholar]
- Bierman E. L., Porte D., Jr Carbohydrate intolerance and lipemia. Ann Intern Med. 1968 Apr;68(4):926–933. doi: 10.7326/0003-4819-68-4-926. [DOI] [PubMed] [Google Scholar]
- Boberg J., Augustin J., Baginsky M. L., Tejada P., Brown W. V. Quantitative determination of hepatic and lipoprotein lipase activities from human postheparin plasma. J Lipid Res. 1977 Jul;18(4):544–547. [PubMed] [Google Scholar]
- Boberg J., Carlson L. A., Freyschuss U. Determination of splanchnic secretion rate of plasma triglycerides and of total and splanchnic turnover of plasma free fatty acids in man. Eur J Clin Invest. 1972 Mar;2(3):123–132. doi: 10.1111/j.1365-2362.1972.tb00580.x. [DOI] [PubMed] [Google Scholar]
- Boberg J., Carlson L. A., Freyschuss U., Lassers B. W., Wahlqvist M. L. Splanchnic secretion rates of plasma triglycerides and total and splanchnic turnover of plasma free fatty acids in men with normo- and hypertriglyceridaemia. Eur J Clin Invest. 1972 Nov;2(6):454–466. doi: 10.1111/j.1365-2362.1972.tb00677.x. [DOI] [PubMed] [Google Scholar]
- CORVILAIN J., LOEB H., CHAMPENOIS A., ABRAMOW M. Effect of fasting on levels of plasma-nonesterified fatty acids in normal children, normal adults, and obese adults. Lancet. 1961 Mar 11;1(7176):534–535. doi: 10.1016/s0140-6736(61)91601-4. [DOI] [PubMed] [Google Scholar]
- Chait A., Hazzard W. R., Albers J. J., Kushwaha R. P., Brunzell J. D. Impaired very low density lipoprotein and triglyceride removal in broad beta disease: comparison with endogenous hypertriglyceridemia. Metabolism. 1978 Sep;27(9):1055–1066. doi: 10.1016/0026-0495(78)90151-8. [DOI] [PubMed] [Google Scholar]
- DOLE V. P. A relation between non-esterified fatty acids in plasma and the metabolism of glucose. J Clin Invest. 1956 Feb;35(2):150–154. doi: 10.1172/JCI103259. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EDELMAN I. S., LEIBMAN J. Anatomy of body water and electrolytes. Am J Med. 1959 Aug;27:256–277. doi: 10.1016/0002-9343(59)90346-8. [DOI] [PubMed] [Google Scholar]
- Eisenberg S., Bilheimer D. W., Levy R. I., Lindgren F. T. On the metabolic conversion of human plasma very low density lipoprotein to low density lipoprotein. Biochim Biophys Acta. 1973 Dec 20;326(3):361–377. doi: 10.1016/0005-2760(73)90138-0. [DOI] [PubMed] [Google Scholar]
- FARQUHAR J. W., GROSS R. C., WAGNER R. M., REAVEN G. M. VALIDATION OF AN INCOMPLETELY COUPLED TWO-COMPARTMENT NONRECYCLING CATENARY MODEL FOR TURNOVER OF LIVER AND PLASMA TRIGLYCERIDE IN MAN. J Lipid Res. 1965 Jan;6:119–134. [PubMed] [Google Scholar]
- Faergeman O., Sata T., Kane J. P., Havel R. J. Metabolism of apoprotein B of plasma very low density lipoproteins in the rat. J Clin Invest. 1975 Dec;56(6):1396–1403. doi: 10.1172/JCI108220. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farquhar J. W., Frank A., Gross R. C., Reaven G. M. Glucose, insulin, and triglyceride responses to high and low carbohydrate diets in man. J Clin Invest. 1966 Oct;45(10):1648–1656. doi: 10.1172/JCI105472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ford S., Jr, Bozian R. C., Knowles H. C., Jr Interactions of obesity, and glucose and insulin levels in hypertriglyceridemia. Am J Clin Nutr. 1968 Sep;21(9):904–910. doi: 10.1093/ajcn/21.9.904. [DOI] [PubMed] [Google Scholar]
- Grundy S. M. Effects of polyunsaturated fats on lipid metabolism in patients with hypertriglyceridemia. J Clin Invest. 1975 Feb;55(2):269–282. doi: 10.1172/JCI107930. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grundy S. M., Mok H. Y. Chylomicron clearance in normal and hyperlipidemic man. Metabolism. 1976 Nov;25(11):1225–1239. doi: 10.1016/s0026-0495(76)80006-6. [DOI] [PubMed] [Google Scholar]
- Havel R. J., Kane J. P., Balasse E. O., Segel N., Basso L. V. Splanchnic metabolism of free fatty acids and production of triglycerides of very low density lipoproteins in normotriglyceridemic and hypertriglyceridemic humans. J Clin Invest. 1970 Nov;49(11):2017–2035. doi: 10.1172/JCI106422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KNITTLE J. L., AHRENS E. H., Jr CARBOHYDRATE METABOLISM IN TWO FORMS OF HYPERGLYCERIDEMIA. J Clin Invest. 1964 Mar;43:485–495. doi: 10.1172/JCI104934. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Letarte J., Fraser T. R. Stimulation by insulin of the incorporation of U-14C-glucose into lipids released by the liver. Diabetologia. 1969 Oct;5(5):358–359. doi: 10.1007/BF00452914. [DOI] [PubMed] [Google Scholar]
- Miller H. I., Bortz W. M., Durham B. C. The rate of appearance of FFA in plasma triglyceride of normal and obese subjects. Metabolism. 1968 Jun;17(6):515–521. doi: 10.1016/0026-0495(68)90043-7. [DOI] [PubMed] [Google Scholar]
- Myers L. H., Phillips N. R., Havel R. J. Mathematical evaluation of methods for estimation of the concentration of the major lipid components of human serum lipoproteins. J Lab Clin Med. 1976 Sep;88(3):491–505. [PubMed] [Google Scholar]
- Nestel P. J. Triglyceride turnover in coronary heart disease and the effect of dietary carbohydrate. Clin Sci. 1966 Aug;31(1):31–38. [PubMed] [Google Scholar]
- Nestel P. J. Triglyceride turnover in man. Effects of dietary carbohydrate. Prog Biochem Pharmacol. 1973;8:125–160. [PubMed] [Google Scholar]
- Nestel P. J., Whyte H. M. Plasma free fatty acid and triglyceride turnover in obesity. Metabolism. 1968 Dec;17(12):1122–1128. doi: 10.1016/0026-0495(68)90092-9. [DOI] [PubMed] [Google Scholar]
- Nikkilä E. A. Control of plasma and liver triglyceride kinetics by carbohydrate metabolism and insulin. Adv Lipid Res. 1969;7:63–134. doi: 10.1016/b978-0-12-024907-7.50009-9. [DOI] [PubMed] [Google Scholar]
- Nikkilä E. A., Huttunen J. K., Ehnholm C. Effect of clofibrate on postheparin plasma triglyceride lipase activities in patients with hypertriglyceridemia. Metabolism. 1977 Feb;26(2):179–186. doi: 10.1016/0026-0495(77)90053-1. [DOI] [PubMed] [Google Scholar]
- Nikkilä E. A., Kekki M. Plasma endogenous triglyceride transport in hypertriglyceridaemia and effect of a hypolipidaemic drug (SU-13437). Eur J Clin Invest. 1972 Jun;2(4):231–238. doi: 10.1111/j.1365-2362.1972.tb00649.x. [DOI] [PubMed] [Google Scholar]
- Nikkilä E. A., Kekki M. Plasma triglyceride metabolism in thyroid disease. J Clin Invest. 1972 Aug;51(8):2103–2114. doi: 10.1172/JCI107017. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nikkilä E. A., Kekki M. Polymorphism of plasma triglyceride kinetics in normal human adult subjects. Acta Med Scand. 1971 Jul-Aug;190(1-2):49–59. doi: 10.1111/j.0954-6820.1971.tb07395.x. [DOI] [PubMed] [Google Scholar]
- OPIE L. H., WALFISH P. G. Plasma free fatty acid concentrations in obesity. N Engl J Med. 1963 Apr 4;268:757–760. doi: 10.1056/NEJM196304042681404. [DOI] [PubMed] [Google Scholar]
- Olefsky J., Farquhar J. W., Reaven G. M. Sex difference in the kinetics of triglyceride metabolism in normal and hypertriglyceridaemic human subjects. Eur J Clin Invest. 1974 Apr;4(2):121–127. doi: 10.1111/j.1365-2362.1974.tb00382.x. [DOI] [PubMed] [Google Scholar]
- Porte D., Jr, Bierman E. L. The effect of heparin infusion on plasma triglyceride in vivo and in vitro with a method for calculating triglyceride turnover. J Lab Clin Med. 1969 Apr;73(4):631–648. [PubMed] [Google Scholar]
- Quarfordt S. H., Frank A., Shames D. M., Berman M., Steinberg D. Very low density lipoprotein triglyceride transport in type IV hyperlipoproteinemia and the effects of carbohydrate-rich diets. J Clin Invest. 1970 Dec;49(12):2281–2297. doi: 10.1172/JCI106448. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reardon M. F., Fidge N. H., Nestel P. J. Catabolism of very low density lipoprotein B apoprotein in man. J Clin Invest. 1978 Mar;61(3):850–860. doi: 10.1172/JCI108999. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reaven G. M., Bernstein R. M. Effect of obesity on the relationship between very low density lipoprotein production rate and plasma triglyceride concentration in normal and hypertriglyceridemic subjects. Metabolism. 1978 Sep;27(9):1047–1054. doi: 10.1016/0026-0495(78)90150-6. [DOI] [PubMed] [Google Scholar]
- Reaven G. M., Hill D. B., Gross R. C., Farquhar J. W. Kinetics of triglyceride turnover of very low density lipoproteins of human plasma. J Clin Invest. 1965 Nov;44(11):1826–1833. doi: 10.1172/JCI105290. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reaven G. M., Lerner R. L., Stern M. P., Farquhar J. W. Role of insulin in endogenous hypertriglyceridemia. J Clin Invest. 1967 Nov;46(11):1756–1767. doi: 10.1172/JCI105666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robertson R. P., Gavareski D. J., Henderson J. D., Porte D., Jr, Bierman E. L. Accelerated triglyceride secretion. A metabolic consequence of obesity. J Clin Invest. 1973 Jul;52(7):1620–1626. doi: 10.1172/JCI107340. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ruderman N. B., Jones A. L., Krauss R. M., Shafrir E. A biochemical and morphologic study of very low density lipoproteins in carbohydrate-induced hypertriglyceridemia. J Clin Invest. 1971 Jun;50(6):1355–1368. doi: 10.1172/JCI106615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ryan W. G., Schwartz T. B. Dynamics of plasma triglyceride turnover in man. Metabolism. 1965 Dec;14(12):1243–1254. doi: 10.1016/s0026-0495(65)80004-x. [DOI] [PubMed] [Google Scholar]
- Sailer S., Sandhofer F., Braunsteiner H. Umsatzraten für freie Fettsäuren und Triglyceride im Plasma bei essentieller Hyperlipämie. Klin Wochenschr. 1966 Sep 1;44(17):1032–1036. doi: 10.1007/BF01878782. [DOI] [PubMed] [Google Scholar]
- Sigurdsson G., Nicoll A., Lewis B. Conversion of very low density lipoprotein to low density lipoprotein. A metabolic study of apolipoprotein B kinetics in human subjects. J Clin Invest. 1975 Dec;56(6):1481–1490. doi: 10.1172/JCI108229. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wolfe B. M., Ahuja S. P. Effects of intravenously administered fructose and glucose on splanchnic secretion of plasma triglycerides in hypertriglyceridemic men. Metabolism. 1977 Sep;26(9):963–978. doi: 10.1016/0026-0495(77)90014-2. [DOI] [PubMed] [Google Scholar]
- Zech L. A., Grundy S. M., Steinberg D., Berman M. Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects. J Clin Invest. 1979 Jun;63(6):1262–1273. doi: 10.1172/JCI109421. [DOI] [PMC free article] [PubMed] [Google Scholar]