Historical Perspective: Milk Lipid Globules and Their Surrounding Membrane: A Brief History and Perspectives for Future Research

  • Thomas W. Keenan


Most of the lipids in milk are triacylglycerols that occur in globules surrounded by a membrane derived from cellular membranes. This membrane, the milk-fat or milk-lipid globule membrane (MLGM),2 surrounds globules during the process of their secretion from the cell. The nature and cellular origin of the milk lipid globule membrane has been the subject of a considerable amount of research. Milk lipid globules originate as very small lipid droplets formed on or in the endoplasmic reticulum followed by release into the cytosol. These droplets consist of a triacylglycerol-rich core coated with a layer of proteins and polar lipids. How these droplets are formed, how they can grow in volume, how they move through the cell, and how they are secreted are questions that have been the basis for a number of investigations. While the general outlines of droplet formation, growth, movement, and secretion are known, virtually no molecular details of any of these processes have been elucidated. In this article I have presented a brief historical account of research on milk fat globules, their surrounding membrane, and on aspects of the intracellular origin, growth, and secretion of milk lipid globules. I have also attempted to call attention to those areas where further research is needed to gain a better understanding of the processes involved.

milk lipid globules milk lipid globule membrane cytosolic lipid droplets endoplasmic reticulum plasma membrane 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. R. Brunner (1974). Physical equilibria in milk:The lipid phase. In B. H. Webb, A. H. Johnson, and J. A. Alford (eds.), Fundamentals of Dairy Chemistry, 2nd ed., Avi, Westport, CT, pp. 474-602.Google Scholar
  2. 2.
    N. King (1955). The Milk Fat Globule Membrane, Commonwealth Agricultural Bureaux, Farnham Royal, Bucks, England.Google Scholar
  3. 3.
    W. Bargmann and A. Knoop (1959). Ñber die morphologie der milchsekretion. Light-und electronenmikroskopische studien an der milchdrüse der ratte. Z. Zellforsch. Mikrosk. Anat. 49:344-388.PubMedGoogle Scholar
  4. 4.
    W. Bargmann, K. Fleischauer, and A. Knoop (1961). Ñber die morphologie der milchsekretion. I. Zugleich eine kritik am schema der sekretionsmorphologie. Z. Zellforsch. Mikrosk. Anat. 53:545-568.PubMedGoogle Scholar
  5. 5.
    S. R. Wellings, K. B. DeOme, and D. R. Pitelka (1960). Electron microscopy of milk secretion in the mammary gland of the C3H/Crgl mouse. I. Cytomorphology of the prelactating and the lactating gland. J. Natl. Cancer Inst. 25:393-421.PubMedGoogle Scholar
  6. 6.
    S. R. Wellings, D. W. Greenbaum, and K. B. DeOme (1960). Electron microscopy of milk secretion in the mammary gland of the C3H/Crgl mouse. II. Identification of fat and protein particles in milk and in tissue. J. Natl. Cancer Inst. 25:423-437.PubMedGoogle Scholar
  7. 7.
    K. H. Hollman (1959). L'ultrastructure de la glande mammaire normale de la souris en lactation. Etudie au microscope electronique. J. Ultrastruct. Res. 2:423-443.Google Scholar
  8. 8.
    J. D. Feldman (1961). Fine structure of the cow's udder during gestation and lactation. Lab. Invest. 10:238-255.PubMedGoogle Scholar
  9. 9.
    I. H. Mather and T. W. Keenan (1998). Origin and secretion of milk lipids. J. Mammary Gland Biol. Neoplasia 3:259-273.PubMedGoogle Scholar
  10. 10.
    F. B. P. Wooding (1977). Comparative mammary fine structure. In M. Peaker (ed.), Comparative Aspects of Lactation. Academic Press, New York, pp. 1-41.Google Scholar
  11. 11.
    M. J. Bailie and R. K. Morton (1958). Comparative properties of microsomes from cow's milk and from mammary gland. I. Enzymatic activities. II. Chemical composition. Biochem. J. 69:35-51.PubMedGoogle Scholar
  12. 12.
    R. M. Dowben, J. R. Brunner, and D. E. Philpott (1967). Studies on milk fat globule membranes. Biochim. Biophys. Acta 135:1-10.PubMedGoogle Scholar
  13. 13.
    S. Patton and T. W. Keenan (1975). The milk fat globule membrane. Biochim. Biophys. Acta 415:273-309.PubMedGoogle Scholar
  14. 14.
    S. Patton and F. M. Fowkes (1969). The role of the plasma membrane in the secretion of milk fat. J. Theoret. Biol. 15:274-281.Google Scholar
  15. 15.
    K. Kurosumi, Y. Kobayashi, and N. Baba (1968). The fine structure of mammary glands of lactating rats, with special reference to the apocrine secretion. Exp. Cell Res. 50:177-192.PubMedGoogle Scholar
  16. 16.
    M. M. T. Janssen and P. Walstra (1982). Cytoplasmic remnants in milk of certain species. Neth. Milk Dairy J. 36:365-368.Google Scholar
  17. 17.
    T. W. Keenan and S. Patton (1995). The milk lipid globule membrane. In R. G. Jensen (ed.), Handbook of Milk Composition, Academic Press, San Diego, pp. 5-62.Google Scholar
  18. 18.
    F. B. P. Wooding (1971). The mechanism of secretion of the milk fat globule. J. Cell Sci. 9:805-821.PubMedGoogle Scholar
  19. 19.
    F. B. P. Wooding and P. Kemp (1975). Ultrastructure of the milk fat globule membrane with and without triglyceride. Cell Tissue Res. 165:113-127.PubMedGoogle Scholar
  20. 20.
    D. P. Dylewski, C. H. Dapper, H. M. Valivullah, J. T. Deeney, and T. W. Keenan (1984). Morphological and biochemical characterization of possible intracellular precursors of milk lipid globules. Eur. J. Cell Biol. 35:99-111.PubMedGoogle Scholar
  21. 21.
    O. Stein and Y. Stein (1967). Lipid synthesis, intracellular transport and secretion. II. Electron microscopic autoradiographic study of the mouse lactating mammary gland. J. Cell Biol. 34:251-263.PubMedGoogle Scholar
  22. 22.
    S. M. Cooper and M. R. Grigor (1980). Fatty acid specificities of microsomal acyltransferases esterifying positions 1 and 2 of acylglycerols in mammary glands from lactating rats. Biochem. J. 187:289-295.PubMedGoogle Scholar
  23. 23.
    A. Peixoto de Menezes and O. Pinto da Silva (1979). Fat droplet formation in lactating rat mammary gland and rat carcinomas viewed by freeze-fracture. Lab. Invest. 40:545-553.PubMedGoogle Scholar
  24. 24.
    R. G. Saacke and C. W. Heald (1974). Cytological aspects of milk formation and secretion. In B. L. Larson and V. R. Smith (eds.), Lactation, Vol. 2, A comprehensive Treatise, Academic Press, New York, pp. 147-189.Google Scholar
  25. 25.
    R. O. Scow, E. J. Blanchette-Mackie, and L. C. Smith (1980). Transport of lipid across capillary endothelium. Feder. Proc. 39:2610-2617.Google Scholar
  26. 26.
    S. Patton (1973). Origin of the milk lipid globule. J. Amer. Oil Chem. Soc. 50:178-185.Google Scholar
  27. 27.
    H. M. Valivullah, D. R. Bevan, A. Peat, and T. W. Keenan (1988). Milk lipid globules: Control of their size distribution. Proc. Natl. Acad. Sci. U.S.A. 85:8775-8779.PubMedGoogle Scholar
  28. 28.
    B. H. Stemberger and S. Patton (1981). Relationship of size, intracellular location, and time required for secretion of milk fat droplets. J. Dairy Sci. 64:422-426.Google Scholar
  29. 29.
    I. H. Mather (2000). A review and proposed nomenclature for major proteins of the milk-fat globule membrane. J. Dairy Sci. 83:203-247.PubMedGoogle Scholar
  30. 30.
    W. W. Franke, M. R. Lüder, J. Kartenbeck, H. Zerban, and T. W. Keenan (1976). Involvement of vesicle coat material in casein secretion and surface regeneration. J. Cell Biol. 69:173-195.PubMedGoogle Scholar
  31. 31.
    H. W. Heid, M. Schnölzer, and T. W. Keenan (1996). Adipocyte differentiation-related protein is secreted into milk as a constituent of milk lipid globule membrane. Biochem. J. 320:1025-1030.PubMedGoogle Scholar
  32. 32.
    J. T. Deeney, H. M. Valivullah, C. H. Dapper, D. P. Dyelwski, and T. W. Keenan (1975). Microlipid droplets in milk secreting mammary epithelial cells: Evidence that they originate from endoplasmic reticulum and are precursors of milk lipid globules. Eur. J. Cell Biol. 38:16-26.Google Scholar
  33. 33.
    T. W. Keenan, S. Winter, H-R. Rackwitz, and H. W. Heid (2000). Nuclear coactivator protein p100 is present in endoplasmic reticulum and lipid droplets of milk secreting cells. Biochim. Biophys. Acta 1523:84-90.PubMedGoogle Scholar
  34. 34.
    D. Ghosal, D. Ankrapp, and T. W. Keenan (1993). Low molecular mass GTP binding proteins are secreted from mammary epithelial cells in association with lipid globules. Biochim. Biophys. Acta 1168:299-306.PubMedGoogle Scholar
  35. 35.
    V. L. Spitsberg and R. C. Gorewit (1997). In vitro phosphorylated bovine milk fat globule membrane proteins. J. Nutr. Biochem. 8:181-189.Google Scholar
  36. 36.
    E. M. Rohlfs, D. S. Louie, and S. H. Zeisel (1993). Lipid synthesis and secretion by primary cultures of rat mammary epithelial cells. J. Cell. Physiol. 157:469-480.PubMedGoogle Scholar
  37. 37.
    L. F. Hood and S. Patton (1973). Isolation and characterization of intracellular lipid droplets from bovine mammary tissue. J. Dairy Sci. 56:858-863.PubMedGoogle Scholar
  38. 38.
    F. B. P. Wooding (1971). The structure of the milk fat globule membrane. J. Ultrastruct. Res. 37:388-400.PubMedGoogle Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Thomas W. Keenan
    • 1
  1. 1.Department of BiochemistryVirginia Polytechnic Institute and State UniversityBlacksburg

Personalised recommendations