Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 2001 Jun 15;356(Pt 3):821–827. doi: 10.1042/0264-6021:3560821

Superior role of apolipoprotein B48 over apolipoprotein B100 in chylomicron assembly and fat absorption: an investigation of apobec-1 knock-out and wild-type mice.

J S Kendrick 1, L Chan 1, J A Higgins 1
PMCID: PMC1221909  PMID: 11389690

Abstract

Editing of apolipoprotein (apo)-B100 mRNA to yield apo-B48 is a specific and developmentally regulated step in enterocytes of mammals. However, the functional significance of this step is not known. Since mice containing only apo-B100 have not been documented to exhibit any difference in intestinal fat absorption from wild-type mice, the evolutionary advantage of apoB mRNA editing has been questioned. In the present study, we have compared fat absorption and chylomicron assembly in apobec-1 knock-out (KO) or wild-type (WT) mice subjected to different dietary manipulations: low-fat chow, a fat-enriched 'Western' diet and overnight fasting. Experiments in vivo and in vitro revealed differences in the ability of KO and WT enterocytes to assemble and secrete chylomicrons under different dietary conditions. After overnight fasting, chylomicron secretion is reduced considerably in KO compared with WT enterocytes. This is not due to reduced synthesis of apo-B or triacylglycerol (TAG), but appears to be a result of impaired assembly of chylomicrons, so that triacylglycerol accumulates in the enterocytes. After feeding with fat, secretion of chylomicrons enriched in pre-existing TAG is stimulated in KO compared with WT mice. In the present study, we have documented for the first time that apo-B100 is considerably less efficient than apo-B48 in exerting its role in the early stage of chylomicron assembly, which is rate-limiting under conditions of low dietary fat. However, this impairment is overcome by increased TAG stores that stimulate later stages in assembly, which are rate-limiting in the fat-fed state. apo-B mRNA editing may result in more efficient fat absorption, specifically under conditions of food shortage or low-fat content, and thus provide an evolutionary advantage.

Full Text

The Full Text of this article is available as a PDF (258.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cartwright I. J., Higgins J. A. Increased dietary triacylglycerol markedly enhances the ability of isolated rabbit enterocytes to secrete chylomicrons: an effect related to dietary fatty acid composition. J Lipid Res. 1999 Oct;40(10):1858–1866. [PubMed] [Google Scholar]
  2. Cartwright I. J., Higgins J. A. Isolated rabbit enterocytes as a model cell system for investigations of chylomicron assembly and secretion. J Lipid Res. 1999 Jul;40(7):1357–1365. [PubMed] [Google Scholar]
  3. Cartwright I. J., Higgins J. A., Wilkinson J., Bellavia S., Kendrick J. S., Graham J. M. Investigation of the role of lipids in the assembly of very low density lipoproteins in rabbit hepatocytes. J Lipid Res. 1997 Mar;38(3):531–545. [PubMed] [Google Scholar]
  4. Cartwright I. J., Plonné D., Higgins J. A. Intracellular events in the assembly of chylomicrons in rabbit enterocytes. J Lipid Res. 2000 Nov;41(11):1728–1739. [PubMed] [Google Scholar]
  5. Chen S. H., Habib G., Yang C. Y., Gu Z. W., Lee B. R., Weng S. A., Silberman S. R., Cai S. J., Deslypere J. P., Rosseneu M. Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science. 1987 Oct 16;238(4825):363–366. doi: 10.1126/science.3659919. [DOI] [PubMed] [Google Scholar]
  6. Frost S. C., Clark W. A., Wells M. A. Studies on fat digestion, absorption, and transport in the suckling rat. IV. In vivo rates of triacylglycerol secretion by intestine and liver. J Lipid Res. 1983 Jul;24(7):899–903. [PubMed] [Google Scholar]
  7. Graham J. M., Higgins J. A., Gillott T., Taylor T., Wilkinson J., Ford T., Billington D. A novel method for the rapid separation of plasma lipoproteins using self-generating gradients of iodixanol. Atherosclerosis. 1996 Jul;124(1):125–135. doi: 10.1016/0021-9150(96)05797-8. [DOI] [PubMed] [Google Scholar]
  8. Hamilton R. L., Wong J. S., Cham C. M., Nielsen L. B., Young S. G. Chylomicron-sized lipid particles are formed in the setting of apolipoprotein B deficiency. J Lipid Res. 1998 Aug;39(8):1543–1557. [PubMed] [Google Scholar]
  9. Hirano K., Young S. G., Farese R. V., Jr, Ng J., Sande E., Warburton C., Powell-Braxton L. M., Davidson N. O. Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48. J Biol Chem. 1996 Apr 26;271(17):9887–9890. doi: 10.1074/jbc.271.17.9887. [DOI] [PubMed] [Google Scholar]
  10. Hussain M. M. A proposed model for the assembly of chylomicrons. Atherosclerosis. 2000 Jan;148(1):1–15. doi: 10.1016/s0021-9150(99)00397-4. [DOI] [PubMed] [Google Scholar]
  11. Hussain M. M., Kancha R. K., Zhou Z., Luchoomun J., Zu H., Bakillah A. Chylomicron assembly and catabolism: role of apolipoproteins and receptors. Biochim Biophys Acta. 1996 May 20;1300(3):151–170. doi: 10.1016/0005-2760(96)00041-0. [DOI] [PubMed] [Google Scholar]
  12. Kumar N. S., Mansbach C. M., 2nd Prechylomicron transport vesicle: isolation and partial characterization. Am J Physiol. 1999 Feb;276(2 Pt 1):G378–G386. doi: 10.1152/ajpgi.1999.276.2.G378. [DOI] [PubMed] [Google Scholar]
  13. Kumar N. S., Mansbach C. M. Determinants of triacylglycerol transport from the endoplasmic reticulum to the Golgi in intestine. Am J Physiol. 1997 Jul;273(1 Pt 1):G18–G30. doi: 10.1152/ajpgi.1997.273.1.G18. [DOI] [PubMed] [Google Scholar]
  14. Mansbach C. M., 2nd, Nevin P. Intracellular movement of triacylglycerols in the intestine. J Lipid Res. 1998 May;39(5):963–968. [PubMed] [Google Scholar]
  15. Morrison J. R., Pászty C., Stevens M. E., Hughes S. D., Forte T., Scott J., Rubin E. M. Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7154–7159. doi: 10.1073/pnas.93.14.7154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nakamuta M., Chang B. H., Zsigmond E., Kobayashi K., Lei H., Ishida B. Y., Oka K., Li E., Chan L. Complete phenotypic characterization of apobec-1 knockout mice with a wild-type genetic background and a human apolipoprotein B transgenic background, and restoration of apolipoprotein B mRNA editing by somatic gene transfer of Apobec-1. J Biol Chem. 1996 Oct 18;271(42):25981–25988. doi: 10.1074/jbc.271.42.25981. [DOI] [PubMed] [Google Scholar]
  17. Osuga J., Yagyu H., Ohashi K., Harada K., Yazaki Y., Yamada N., Ishibashi S. Effects of apo E deficiency on plasma lipid levels in mice lacking APOBEC-1. Biochem Biophys Res Commun. 1997 Jul 18;236(2):375–378. doi: 10.1006/bbrc.1997.6951. [DOI] [PubMed] [Google Scholar]
  18. Plonne D., Cartwright I., Linss W., Dargel R., Graham J. M., Higgins J. A. Separation of the intracellular secretory compartment of rat liver and isolated rat hepatocytes in a single step using self-generating gradients of iodixanol. Anal Biochem. 1999 Dec 1;276(1):88–96. doi: 10.1006/abio.1999.4311. [DOI] [PubMed] [Google Scholar]
  19. Powell L. M., Wallis S. C., Pease R. J., Edwards Y. H., Knott T. J., Scott J. A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell. 1987 Sep 11;50(6):831–840. doi: 10.1016/0092-8674(87)90510-1. [DOI] [PubMed] [Google Scholar]
  20. Young S. G., Cham C. M., Pitas R. E., Burri B. J., Connolly A., Flynn L., Pappu A. S., Wong J. S., Hamilton R. L., Farese R. V., Jr A genetic model for absent chylomicron formation: mice producing apolipoprotein B in the liver, but not in the intestine. J Clin Invest. 1995 Dec;96(6):2932–2946. doi: 10.1172/JCI118365. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES