Abstract
The present study was undertaken to evaluate quantitatively the turnover of serum triacylglycerol (triglyceride) in the starved rat and to determine whether serum triacylglycerol recycled to liver contributes a significant fraction of the total hepatic triacylglycerol turnover. Serum was labelled in vitro with [3H]trioleoylglycerol (glycerol [3H]trioleate) to provide uniform labelling of all lipoprotein species. By using the curves describing disappearance of isotope from serum and its appearance in liver, rate constants for movement of triacylglycerol out of serum (0.29 min-1) and the uptake of serum triacylglycerol by liver (0.22 min-1) were calculated. The total rate of movement (flux) of triacylglycerol in these processes, the product of rate constant and serum pool size, was calculated to be 0.39 and 0.29 mg/min per 100 g body wt. respectively. A model is postulated for whole-body triacylglycerol metabolism consistent with the present data as well as most observations in the literature. From the model it can be predicted that: (1) the entire turnover of liver triacylglycerol in the starved rat can be accounted for on the basis of contributions from serum non-esterified fatty acid and serum triacylglycerol; (2) the entire turnover of the serum triacylglycerol pool can be accounted for quantitatively on the basis of contributions from intestine and liver; (3) the release rate for triacylglycerol from liver should be 0.34 to 0.35 mg/min per 100 g body wt.; (4) triacylglycerol synthesized by liver from non-esterified fatty acid of serum and by intestine can account quantitatively for the irreversible disposal rate of triacylglycerol from serum.
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- AVIGAN J. A method for incorporating cholesterol and other lipides into serum lipoproteins in vitro. J Biol Chem. 1959 Apr;234(4):787–790. [PubMed] [Google Scholar]
- Abrams M. A., Cooper C. Mechanism of increased hepatic uptake of unesterified fatty acid from serum of ethanol-treated rats. Biochem J. 1976 Apr 15;156(1):47–54. doi: 10.1042/bj1560047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Abrams M. A., Cooper C. Quantitative analysis of metabolism of hepatic triglyceride in ethanol-treated rats. Biochem J. 1976 Apr 15;156(1):33–46. doi: 10.1042/bj1560033. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
- Baxter J. Origin and characteristics of endogenous lipid in thoracic duct lymph in rat. J Lipid Res. 1966 Jan;7(1):158–166. [PubMed] [Google Scholar]
- Belfrage P., Elovson J., Olivecrona T. Radioactivity in blood and liver partial glycerides, and liver phospholipids after intravenous administration to carbohydrate-fed rats of chyle containing double-labeled triglycerides. Biochim Biophys Acta. 1965 Jul 7;106(1):45–55. doi: 10.1016/0005-2760(65)90094-9. [DOI] [PubMed] [Google Scholar]
- Belfrage P. Metabolism of chyle triglycerides in the liver. I. Studies on the mechanisms for liver uptake of intravenously injected, glycerol- and fatty acid-labeled chyle in the carbohydrate-fed rat. Biochim Biophys Acta. 1966 Dec 7;125(3):474–484. [PubMed] [Google Scholar]
- Brenneman D. E., McGee R., Spector A. A. Cholesterol metabolism in the Ehrlich ascites tumor. Cancer Res. 1974 Oct;34(10):2605–2611. [PubMed] [Google Scholar]
- Brenneman D. E., Spector A. A. Utilization of ascites plasma very low density lipoprotein triglycerides by Ehrlich cells. J Lipid Res. 1974 Jul;15(4):309–316. [PubMed] [Google Scholar]
- Cenedella R. J., Crouthamel W. G. Halofenate and clofibrate: mechanism of hypotriglyceridemic action in the rat. J Lipid Res. 1976 Mar;17(2):156–166. [PubMed] [Google Scholar]
- Eaton R. P., Berman M., Steinberg D. Kinetic studies of plasma free fatty acid and triglyceride metabolism in man. J Clin Invest. 1969 Aug;48(8):1560–1579. doi: 10.1172/JCI106122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elovson J., Olivecrona T., Belfrage P. Metabolism in the rat of chyle obtained after feeding hydrogenated coconut oil labeled with stearic acid. Biochim Biophys Acta. 1965 Jul 7;106(1):34–44. doi: 10.1016/0005-2760(65)90093-7. [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]
- FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
- FRENCH J. E., MORRIS B. The tissue distribution and oxidation of 14C-labelled chylomicron fat injected intravenously in rats. J Physiol. 1958 Feb 17;140(2):262–271. doi: 10.1113/jphysiol.1958.sp005932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Faergeman O., Havel R. J. Metabolism of cholesteryl esters of rat very low density lipoproteins. J Clin Invest. 1975 Jun;55(6):1210–1218. doi: 10.1172/JCI108039. [DOI] [PMC free article] [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]
- Felts J. M. The metabolism of chylomicron triglyceride fatty acids by perfused rat livers and by intact rats. Ann N Y Acad Sci. 1965 Oct 8;131(1):24–33. doi: 10.1111/j.1749-6632.1965.tb34776.x. [DOI] [PubMed] [Google Scholar]
- GREEN C., WEBB J. A. THE UPTAKE OF CHYLOMICRON FATTY ACIDS BY ISOLATED LIVER CELLS. Biochim Biophys Acta. 1964 Aug 5;84:404–411. doi: 10.1016/0926-6542(64)90004-6. [DOI] [PubMed] [Google Scholar]
- HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harris K. L., Felts J. M. Kinetics of chylomicron triglyceride removal from plasma in rats: a comparison of the anesthetized and the unanesthetized states. J Lipid Res. 1970 Mar;11(2):75–81. [PubMed] [Google Scholar]
- Havel R. J., Kane J. P. Quantification of triglyceride transport in blood plasma: a critical analysis. Fed Proc. 1975 Dec;34(13):2250–2257. [PubMed] [Google Scholar]
- Higgins J. A. Forces involved in chylomicron binding by isolated cells of rat liver. J Lipid Res. 1967 Nov;8(6):636–641. [PubMed] [Google Scholar]
- Higgins J. A., Green C. The uptake of lipids by rat liver cells. Biochem J. 1966 Jun;99(3):631–639. doi: 10.1042/bj0990631. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kissebah A. H., Adams P. W., Wynn V. Plasma free fatty acid and triglyceride transport kinetics in man. Clin Sci Mol Med. 1974 Sep;47(3):259–278. doi: 10.1042/cs0470259. [DOI] [PubMed] [Google Scholar]
- Klauda H. C., Zilversmit D. B. Influx of cholesterol into plasma in rabbits with fasting hyperbetalipoproteinemia. J Lipid Res. 1974 Nov;15(6):593–601. [PubMed] [Google Scholar]
- Levy R. I., Bilheimer D. W., Eisenberg S. The structure and metabolism of chylomicrons and very low density lipoproteins (VLDL). Biochem Soc Symp. 1971;(33):3–17. [PubMed] [Google Scholar]
- Lowenstein J. M. Effect of (-)-hydroxycitrate on fatty acid synthesis by rat liver in vivo. J Biol Chem. 1971 Feb 10;246(3):629–632. [PubMed] [Google Scholar]
- Mistilis S. P., Ockner R. K. Effects of ethanol on endogenous lipid and lipoprotein metabolism in small intestine. J Lab Clin Med. 1972 Jul;80(1):34–46. [PubMed] [Google Scholar]
- Naito H. K., Wada M., Ehrhart L. A., Lewis L. A. Polyacrylamide-gel disc-electrophoresis as a screening procedure for serum lipoprotein abnormalities. Clin Chem. 1973 Feb;19(2):228–234. [PubMed] [Google Scholar]
- Nestel P. J., Havel R. J., Bezman A. SITES OF INITIAL REMOVAL OF CHYLOMICRON TRIGLYCERIDE FATTY ACIDS FROM THE BLOOD. J Clin Invest. 1962 Oct;41(10):1915–1921. doi: 10.1172/JCI104648. [DOI] [PMC free article] [PubMed] [Google Scholar]
- OLIVECRONA T., BELFRAGE P. MECHANISMS FOR REMOVAL OF CHYLE TRIGLYCERIDE FROM THE CIRCULATING BLOOD AS STUDIED WITH (14C)GLYCEROL AND (3H)PALMITIC ACID- LABELED CHYLE. Biochim Biophys Acta. 1965 Feb 1;98:81–93. doi: 10.1016/0005-2760(65)90013-5. [DOI] [PubMed] [Google Scholar]
- Ockner R. K., Hughes F. B., Isselbacher K. J. Very low density lipoproteins in intestinal lymph: origin, composition, and role in lipid transport in the fasting state. J Clin Invest. 1969 Nov;48(11):2079–2088. doi: 10.1172/JCI106174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ontko J. A. Chylomicron, free fatty acid and ketone body metabolism of isolated liver cells and liver homogenates. Biochim Biophys Acta. 1967 Feb 14;137(1):13–22. doi: 10.1016/0005-2760(67)90003-3. [DOI] [PubMed] [Google Scholar]
- Ontko J. A., Zilversmit D. B. Metabolism of chylomicrons by the isolated rat liver. J Lipid Res. 1967 Mar;8(2):90–96. [PubMed] [Google Scholar]
- Palmer J. F., Cooper C., Shipley R. A. Rate of release of hepatic triacylglycerol into serum in the starved rat. Biochem J. 1978 May 15;172(2):219–226. doi: 10.1042/bj1720219. [DOI] [PMC free article] [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]
- Quarfordt S. H., Goodman D. S. Metabolism of doubly-labeled chylomicron cholesteryl esters in the rat. J Lipid Res. 1967 May;8(3):264–273. [PubMed] [Google Scholar]
- ROHEIM P. S., MILLER L., EDER H. A. THE FORMATION OF PLASMA LIPOPROTEINS FROM APOPROTEIN IN PLASMA. J Biol Chem. 1965 Jul;240:2994–3001. [PubMed] [Google Scholar]
- Recknagel R. O. Carbon tetrachloride hepatotoxicity. Pharmacol Rev. 1967 Jun;19(2):145–208. [PubMed] [Google Scholar]
- Redgrave T. G., Roberts D. C., West C. E. Separation of plasma lipoproteins by density-gradient ultracentrifugation. Anal Biochem. 1975 May 12;65(1-2):42–49. doi: 10.1016/0003-2697(75)90488-1. [DOI] [PubMed] [Google Scholar]
- Roheim P. S., Edelstein D., Pinter G. G. Apolipoproteins in rat serum and renal lymph. Proc Natl Acad Sci U S A. 1976 May;73(5):1757–1760. doi: 10.1073/pnas.73.5.1757. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SCHOTZ M. C., BAKER N., CHAVEZ M. N. EFFECT OF CARBON TETRACHLORIDE INGESTION ON LIVER AND PLASMA TRIGLYCERIDE TURNOVER RATES. J Lipid Res. 1964 Oct;5:569–577. [PubMed] [Google Scholar]
- STEIN Y., SHAPIRO B. Uptake and metabolism of triglycerides by the rat liver. J Lipid Res. 1960 Jul;1:326–331. [PubMed] [Google Scholar]
- Schotz M. C., Arnesjö B., Olivecrona T. The role of the liver in the uptake of plasma and chyle triglycerides in the rat. Biochim Biophys Acta. 1966 Dec 7;125(3):485–495. doi: 10.1016/0005-2760(66)90037-3. [DOI] [PubMed] [Google Scholar]
- Shames D. M., Frank A., Steinberg D., Berman M. Transport of plasma free fatty acids and triglycerides in man: a theoretical analysis. J Clin Invest. 1970 Dec;49(12):2298–2314. doi: 10.1172/JCI106449. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Soloni F. G. Simplified manual micromethod for determination of serum triglycerides. Clin Chem. 1971 Jun;17(6):529–534. [PubMed] [Google Scholar]
- Stein O., Rachmilewitz D., Sanger L., Eisenberg S., Stein Y. Metabolism of iodinated very low density lipoprotein in the rat. Autoradiographic localization in the liver. Biochim Biophys Acta. 1974 Aug 22;360(2):205–216. doi: 10.1016/0005-2760(74)90170-2. [DOI] [PubMed] [Google Scholar]
- Stein O., Stein Y., Goodman D. S., Fidge N. H. The metabolism of chylomicron cholesteryl ester in rat liver. A combined radioautographic-electron microscopic and biochemical study. J Cell Biol. 1969 Dec;43(3):410–431. doi: 10.1083/jcb.43.3.410. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stein O., Stein Y. The role of the liver in the metabolism of chylomicrons, studied by electron microscopic autoradiography. Lab Invest. 1967 Oct;17(4):436–446. [PubMed] [Google Scholar]
- Windmueller H. G., Levy R. I. Production of beta-lipoprotein by intestine in the rat. J Biol Chem. 1968 Sep 25;243(18):4878–4884. [PubMed] [Google Scholar]