Skip to main content
SpringerLink
Log in

Variablity of the intestinal uptake of lipids is genetically determined in mice

  • Published:
Lipids

Abstract

The response of the plasma cholesterol concentration to changes in dietary lipids varies widely in humans and animals. There are variations in the in vivo absorption of cholesterol between different strains of mice. This study was undertaken in three strains of inbred mice to test the hypotheses that: (i) there are strain differences in the in vitro uptake of fatty acids and cholesterol and (ii) the adaptability of the intestine to respond to variations in dietary lipids is genetically determined. An in vitro intestinal ring technique was used to assess the uptake of medium- and long-chain fatty acids and cholesterol into jejunum and ileum of adult DBA/2, C57BL6, and C57L/J mice. The jejunal uptake of cholesterol was similar in C57L/J, DBA/2, or C57BL6 fed ad libitum a low-fat (5.7% fat, no cholesterol) chow diet. This is in contrast to a previous demonstration that in vivo cholesterol absorption was lower in C57L/J than in the other murine strains. The jejunal uptake of several long-chain fatty acids was greater in DBA/2 fed for 4 wk the high-fat (15.8% fat and 1.25% cholesterol) as compared with the low-fat diet. Furthermore, on the high-fat diet, the uptake of many long-chain fatty acids was higher in DBA/2 than in C57BL6 or C57L/J. The differences in cholesterol and fatty acid uptake were not explained by variations in food uptake, body weight gain, or the weight of the intestine. In summary: (i) there are strain differences in the in vitro intestinal uptake of fatty acids but not of cholesterol; (ii) a high-fat diet enhances the uptake of long-chain fatty acids in only one of the three strains examined in this study; and (iii) the pattern of strain- and diet-associated alterations in the in vivo absorption of cholesterol differs from the pattern of changes observed in vitro. We speculate that genetic differences in cholesterol and fatty acid uptake are explained by variations in the expression of protein-mediated components of lipid uptake.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BBM:

brush border membrane

FAT:

fatty acid transporter

UWL:

unstirred water layer

References

  1. Aubert, R., Perdereau, D., Roubiscoul, M., Herzog, J., and Lemonnier, D. (1988) Genetic Variations in Serum Lipid Levels of Inbred Mice and Response to Hypercholesterolemic Diet, Lipids 23, 48–54.

    PubMed  CAS  Google Scholar 

  2. Bhattacharyya, A.K., Baker, H.N., Eggen D.A., Malcolm, G.T., Roheim, P.S., and Strong, J.P. (1989) Effect of Cholesterol Feeding on Lipolytic Activities in High- and Low-Responding Rhesus Monkeys, Arteriosclerosis 9, 380–389.

    PubMed  CAS  Google Scholar 

  3. Bhattacharyya, A.K., and Eggen, D.A. (1988) Studies on the Mechanisms of High Intestinal Absorption of Cholesterol and Campesterol in High-Responding Rhesus Monkeys, Atherosclerosis 72, 109–114.

    Article  PubMed  CAS  Google Scholar 

  4. Kirk, E.A., Moe, G.L., Caldwell, M.T., Lernmark, J.A., Wilson, D.L., and LeBoeuf, R.C. (1995) Hyper- and Hypo-Responsiveness to Dietary Fat and Cholesterol Among Inbred Mice: Searching for Level and Variability Genes, J. Lipid Res. 36, 1522–1532.

    PubMed  CAS  Google Scholar 

  5. McNamura, D.J., Kolb, R., Parker, T.S., Batwin, H., Simon, P., Brown, C.D., and Ahrens, E.H. (1987) Heterogeneity of Cholesterol Responsiveness in Man, J. Clin. Invest. 79, 1729–1739.

    Article  Google Scholar 

  6. Mahley, R.W., Weisgraber, K.H., and Innerarity, T.L. (1974) Canine Lipoproteins and Atherosclerosis II. Characterization of the Plasma Lipoproteins Associated with Atherogenic and Nonatherogenic Hyperlipidemia, Circ. Res. 35, 722–733.

    PubMed  CAS  Google Scholar 

  7. Thurnhofer, H.J., Schnabel, J., Betz, M., Lipka, G., Pidgeon, C., and Hauser, H. (1991) Cholesterol-Transfer Protein Located in the Intestinal Brush-Border Membrane. Partial Purification and Characterization, Biochim. Biophys. Acta 1064, 275–286.

    Article  PubMed  CAS  Google Scholar 

  8. Lipka, G., Schulthess, G., Thurnhofer, H., Wacker, H., Wehrli, E., Zeman, K., Weber, F.E., and Hauser, H. (1995) Characterization of Lipid Exchange Proteins Isolated from Small Intestinal Brush Border Membrane, J. Biol. Chem. 270, 5917–5925.

    Article  PubMed  CAS  Google Scholar 

  9. Overturf, M.L., Smith, S.A., and Gotto, A.M. (1990) Dietary Cholesterol Absorption and Sterol and Bile Acid Excretion in Hypercholesterolemia-Resistant White Rabbits, J. Lipid Res. 31, 2019–2027.

    PubMed  CAS  Google Scholar 

  10. Safonova, L.G., Sviridov, D.D., Roytman, A., Rytikov, F.M., Dolgov, V.V., Nano, J.L., Rampal, P., and Repin, V.S. (1993) Cholesterol Uptake in the Human Intestine, Biochim. Biophys. Acta 1166, 313–316.

    PubMed  CAS  Google Scholar 

  11. Carter, C.P., Howles, P.N., and Hui, D.Y. (1997) Genetic Variation in Cholesterol Absorption Efficiency Among Inbred Strains of Mice, J. Nutr. 127, 1344–1348.

    PubMed  CAS  Google Scholar 

  12. Howles, P.N., Carter, C.P., and Hui, D.Y. (1996) Dietary Free and Esterified Cholesterol Absorption in Cholesterol Esterase (bile salt-stimulated lipase) Gene-Targeted Mice, J. Biol. Chem. 271, 7196–7202.

    Article  PubMed  CAS  Google Scholar 

  13. Perin, N., Keelan, M., Clandinin, M.T., and Thomson, A.B.R. (1997) Ontogeny of Intestinal Absorption Adaptation in Rats in Response to Isocaloric Changes in Dietary Lipids, Am. J. Physiol. 273, G713-G720.

    PubMed  CAS  Google Scholar 

  14. Fingerote, R.J., Doring, K.A., and Thomson, A.B.R. (1994) Gradient for Glucose and Linoleic Acid Uptake Along the Crypt-Villus Axis of Rabbit Jejunal Brush Border Membrane Vesicles, Lipids 29, 117–127.

    PubMed  CAS  Google Scholar 

  15. Tso, P. (1994) Intestinal Lipid Absorption, in Physiology of the Gastrointestinal Tract, pp. 1867–1907, Raven Press, New York.

    Google Scholar 

  16. Thomson, A.B.R., Schoeller, C., Keelan, M., Smith, L., and Clandinin, M.T. (1993) Lipid Absorption: Passing Through the Unstirred Layers, Brush Border Membrane and Beyond, Can. J. Physiol. Pharm. 71, 531–555.

    CAS  Google Scholar 

  17. Schroeder, F., Jefferson, J.R., Powell, D., Incerpi, S., Woodford, J.K., Colles, S.M., Myers-Payne, S., Emge, T., Hebbell, T., and Moncecchi, D. (1993) Expression of Rat L-FABP in Mouse Fibroblasts: Role in Fat Absorption, Mol. Cell. Biochem. 123, 73–83.

    Article  PubMed  CAS  Google Scholar 

  18. Paigen, B. (1995) Genetics of Responsiveness to High-Fat and High-Cholesterol Diets in the Mouse, Am. J. Clin. Nutr. 62, 458S-462S.

    PubMed  CAS  Google Scholar 

  19. Schoeller, C., Keelan, M., Mulvey, G., Stremmel, W., and Thomson, A.B.R. (1995) Oleic Acid Uptake into Rat and Rabbit Jejunal Brush Border Membrane, Biochim. Biophys. Acta 1236, 51–64.

    Article  PubMed  Google Scholar 

  20. Stremmel, W. (1988) Uptake of Fatty Acids by Jeunal Mucosal Cells Is Mediated by a Fatty Acid-Binding Membrane Protein, J. Clin. Invest. 82, 2001–2010.

    PubMed  CAS  Google Scholar 

  21. Poirier, H., Degrace, P., Niot, I., Bernard, A., and Besnard, P. (1996) Localization and Regulation of the Putative Membrane Fatty-Acid Transporter (FAT) in the Small Intestine. Comparison with Fatty Acid-Binding Proteins (FABP), Eur. J. Biochem. 238, 368–373.

    Article  PubMed  CAS  Google Scholar 

  22. Baille, A.G.S., Coburn, C.T., and Abumrad, N.A. (1996) Reversible Binding of Long-Chain Fatty Acids to Purified FAT, the Adipose CD36 Homolog, J. Membr. Biol. 153, 75–81.

    Article  Google Scholar 

  23. Ibrahimi, A., Sfeir, Z., Magharaie, H., Amri, E., Grimaldi, P., and Abumrad, N.A. (1996) Expression of the CD36 Homolog (FAT) in Fibroblast Cells: Effect on Fatty Acid Transport, Proc. Natl. Acad. Sci. USA 93, 2646–2651.

    Article  PubMed  CAS  Google Scholar 

  24. Hediger, M.A., and Rhoads, D.B. (1994) Molecular Physiology of Sodium-Glucose Cotransporters, Physiol. Rev. 74, 993–1026.

    PubMed  CAS  Google Scholar 

  25. Meddings, J.B., and Theisen, S. (1989) Development of Rat Jejunum: Lipid Permeability, Physical Properties, and Chemical Composition, Am. J. Physiol. 256, G931-G940.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nutrition and Metabolism Research Group, Department of Medicine, Division of Gastroenterology, University of Alberta, 519 Robert Newton Research Building, T6G 2C2, Edmonton, Alberta, Canada

    M. Keelan, M. T. Clandinin & A. B. R. Thomson

  2. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 45267, Cincinnati, Ohio

    D. Y. Hui

  3. Department of Medicine, Division of Gastroenterology, McGill University Health Centre, H3G 1A4, Montréal, Québec, Canada

    G. Wild

Authors
  1. M. Keelan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Y. Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Wild
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. T. Clandinin
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. B. R. Thomson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. B. R. Thomson.

About this article

Cite this article

Keelan, M., Hui, D.Y., Wild, G. et al. Variablity of the intestinal uptake of lipids is genetically determined in mice. Lipids 35, 833–837 (2000). https://doi.org/10.1007/S11745-000-0592-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/S11745-000-0592-0

Keywords

Search

Navigation