Abstract
The metabolism of chylomicrons doubly labeled with cholesterol-3H and triglyceride-14C was studied in unanesthetized rats which were absorbing a fatty test meal. 10 min after intravenous injection, 80% of chylomicron cholesteryl ester, but only 20% of chylomicron triglyceride, was found in the liver. Treatment of recipient rats with puromycin to block hepatic triglyceride release did not increase the proportion of chylomicron triglyceride found in the liver.
Rapid partition of chylomicron triglyceride from cholesterol ester also occurred in rats in which the liver had been excluded from the circulation. However, now the cholesteryl ester accumulated in the plasma, whereas triglyceride was cleared by peripheral tissues. Residual labeled cholesterol in the plasma of such rats was shown to be present in particulate form, together with some residual triglyceride. The remnant particles contained about 13% cholesteryl ester. When injected into other rats the remnant particles appeared in the liver more rapidly than did chylomicrons.
These observations were consistent with the hypothesis that the first step in chylomicron metabolism occurred in extrahepatic tissues where a large portion of the triglyceride was removed by the action of lipoprotein lipase. The remnant particles so produced contained the chylomicron cholesteryl ester and residual triglyceride, and they were removed from the plasma by the liver.
Full text
PDF![465](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ef2/322493/0b3c0c1c8f55/jcinvest00219-0057.png)
![466](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ef2/322493/b413eaec92d5/jcinvest00219-0058.png)
![467](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ef2/322493/e8eb387e408d/jcinvest00219-0059.png)
![468](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ef2/322493/1d949b676390/jcinvest00219-0060.png)
![469](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ef2/322493/39d90d4fafa2/jcinvest00219-0061.png)
![470](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ef2/322493/4ae8ee62d640/jcinvest00219-0062.png)
![471](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ef2/322493/ec631013d2ce/jcinvest00219-0063.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BAKER R. D., GUILLET G. G., MAYNES C. C. A cage for restraining rats. J Appl Physiol. 1962 Nov;17:1020–1021. doi: 10.1152/jappl.1962.17.6.1020. [DOI] [PubMed] [Google Scholar]
- BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
- BLOOMFIELD D. K. CHOLESTEROL METABOLISM. 3. ENHANCEMENT OF CHOLESTEROL ABSORPTION AND ACCUMULATION IN SAFFLOWER OIL-FED RATS. J Lab Clin Med. 1964 Oct;64:613–623. [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]
- DILUZIO N. R., RIGGI S. J. THE RELATIVE PARTICIPATION OF HEPATIC PARENCHYMAL AND KUPFFER CELLS IN THE METABOLISM OF CHYLOMICRONS. J Reticuloendothel Soc. 1964 Jul;1:248–263. [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]
- FRIEDMAN M., BYERS S. O., ST GEORGE S. Detection of dietary cholesterol-4-C14 in the hepatic reticulo-endothelial cell of the rat. Am J Physiol. 1956 Jan;184(1):141–144. doi: 10.1152/ajplegacy.1955.184.1.141. [DOI] [PubMed] [Google Scholar]
- GOODMAN D. S. The metabolism of chylomicron cholesterol ester in the rat. J Clin Invest. 1962 Oct;41:1886–1896. doi: 10.1172/JCI104645. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodman D. S. Cholesterol ester metabolism. Physiol Rev. 1965 Oct;45(4):747–839. doi: 10.1152/physrev.1965.45.4.747. [DOI] [PubMed] [Google Scholar]
- HILLYARD L. A., CORNELIUS C. E., CHAIKOFF I. L. Removal by the isolated rat liver of palmitate-1-C14 bound to albumin and of palmitate-1-C14 and cholesterol-4-C14 in chylomicrons from perfusion fluid. J Biol Chem. 1959 Sep;234:2240–2245. [PubMed] [Google Scholar]
- Jones A. L., Ruderman N. B., Herrera M. G. Electron microscopic and biochemical study of lipoprotein synthesis in the isolated perfused rat liver. J Lipid Res. 1967 Sep;8(5):429–446. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- MINARI O., ZILVERSMIT D. B. BEHAVIOR OF DOG LYMPH CHYLOMICRON LIPID CONSTITUENTS DURING INCUBATION WITH SERUM. J Lipid Res. 1963 Oct;4:424–436. [PubMed] [Google Scholar]
- MORRIS B., FRENCH J. E. The uptake and metabolism of 14C labelled chylomicron fat by the isolated perfused liver of the rat. Q J Exp Physiol Cogn Med Sci. 1958 Apr;43(2):180–188. doi: 10.1113/expphysiol.1958.sp001315. [DOI] [PubMed] [Google Scholar]
- NESTEL P. J., HAVEL R. J., BEZMAN A. METABOLISM OF CONSTITUENT LIPIDS OF DOG CHYLOMICRONS. J Clin Invest. 1963 Aug;42:1313–1321. doi: 10.1172/JCI104815. [DOI] [PMC free article] [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]
- 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]
- PINTER G. G., ZILVERSMIT D. B. A gradient centrifugation method for the determination of particle size distribution of chylomicrons and of fat droplets in artificial fat emulsions. Biochim Biophys Acta. 1962 May 7;59:116–127. doi: 10.1016/0006-3002(62)90702-3. [DOI] [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]
- ROBINSON D. S. THE CLEARING FACTOR LIPASE AND ITS ACTION IN THE TRANSPORT OF FATTY ACIDS BETWEEN THE BLOOD AND TISSUES. Adv Lipid Res. 1963;1:133–182. doi: 10.1016/b978-1-4831-9937-5.50010-7. [DOI] [PubMed] [Google Scholar]
- ROHEIM P. S., HAFT D. E., GIDEZ L. I., WHITE A., EDER H. A. PLASMA LIPOPROTEIN METABOLISM IN PERFUSED RAT LIVERS. II. TRANSFER OF FREE AND ESTERIFIED CHOLESTEROL INTO THE PLASMA. J Clin Invest. 1963 Aug;42:1277–1285. doi: 10.1172/JCI104812. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Redgrave T. G., Zilversmit D. B. Does puromycin block release of chylomicrons from the intestine? Am J Physiol. 1969 Aug;217(2):336–340. doi: 10.1152/ajplegacy.1969.217.2.336. [DOI] [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]
- Uarfordt S. H., Goodman D. S. Chylomicron cholesteryl ester metabolism in the perfused rat liver. Biochim Biophys Acta. 1969 Jun 10;176(4):863–872. doi: 10.1016/0005-2760(69)90268-9. [DOI] [PubMed] [Google Scholar]
- VAN HANDEL E., ZILVERSMIT D. B. Micromethod for the direct determination of serum triglycerides. J Lab Clin Med. 1957 Jul;50(1):152–157. [PubMed] [Google Scholar]
- ZLATKIS A., ZAK B., BOYLE A. J. A new method for the direct determination of serum cholesterol. J Lab Clin Med. 1953 Mar;41(3):486–492. [PubMed] [Google Scholar]
- Zilversmit D. B. The composition and structure of lymph chylomicrons in dog, rat, and man. J Clin Invest. 1965 Oct;44(10):1610–1622. doi: 10.1172/JCI105267. [DOI] [PMC free article] [PubMed] [Google Scholar]