Cholesterol transporters in lactating and nonlactating human mammary tissue

In: Handbook of dietary and nutritional aspects of human breast milk
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C. Albrecht
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X. Huang
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E. C. Ontsouka
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In mammals milk is the principal nutrient for neonates at birth. The basic milk composition is similar between different mammals, but the content of individual constituents such as lipids may differ significantly from one species to another. The milk fat fraction is mainly composed of triglycerides which account for more than 95% of the lipids found in human and bovine milk. Though sterols and in particular cholesterol, the predominant milk sterol, represent less than 0.5% of the total milk lipid fraction, they are of ultimate importance for biological processes such as the formation of biological membranes or as precursors for steroid hormone synthesis. Cholesterol found in milk originates either from blood uptake or from local synthesis. This chapter provides an overview of cholesterol exchanges between the blood, the mammary tissue and the milk. The current knowledge on the expression, localization and function of candidate cholesterol transporters in mammary tissues of human, murine and bovine origin is summarized. Different mechanisms of how cholesterol can be transferred via the mammary tissue into milk, and which active cholesterol transporters are likely to play a role in this process will be discussed.

  • Altmann, S.W., Davis, H.R., Jr., Zhu, L.J., Yao, X., Hoos, L.M., Tetzloff, G., Iyer, S.P., Maguire, M., Golovko, A., Zeng, M., Wang, L., Murgolo, N. and Graziano, M.P., 2004. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science 303, 1201-1204.

  • Davies, J. P., Levy, B. and Ioannou, Y.A., 2000. Evidence for a Niemann-pick C (NPC) gene family: identification and characterization of NPC1L1. Genomics 65, 137-145.

  • Farke, C., Viturro, E., Meyer, H.H. and Albrecht, C., 2006. Identification of the bovine cholesterol efflux regulatory protein ABCA1 and its expression in various tissues. Journal of Animal Science 84, 2887-2894.

  • Gofflot, F., Hars, C., Illien, F., Chevy, F., Wolf, C., Picard, J.J. and Roux, C., 2003. Molecular mechanisms underlying limb anomalies associated with cholesterol deficiency during gestation: implications of Hedgehog signaling. Human Molecular Genetics 12, 1187-1198.

  • Isomura, H., Takimoto, H., Miura, F., Kitazawa, S., Takeuchi, T., Itabashi, K. and Kato, N., 2011. Type of milk feeding affects hematological parameters and serum lipid profile in Japanese infants. Pediatrics International 53, 807-813.

  • Jandal, J.M., 1996. Comparative aspects of goat and sheep milk. Small Ruminant Research 22, 177-185.

  • Jensen, R.G., 1996. The lipids in human milk. Progress in Lipid Research 35, 53-92.

  • Jensen, R.G., 2002. The composition of bovine milk lipids: January 1995 to December 2000. Journal of Dairy Science 85, 295-350.

  • Keenan, TW., 2001. Milk lipid globules and their surrounding membrane: a brief history and perspectives for future research. Journal of Mammary Gland Biology and Neoplasia 6, 365-371.

  • Kobayashi, A., Tanezawa, Y., Hirata, T., Shimizu, Y., Misasa, K., Kioka, N., Arai, H., Ueda, K. and Matsuo, M., 2006. Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1. Journal of Lipid Research 47, 1791-1802.

  • Kusuhara, H. and Sugiyama, Y., 2007. ATP-binding cassette, subfamily G (ABCG family). Pflugers Archiv - European Journal of Physiology 453, 735-744.

  • Langmann, T., Klucken, J., Reil, M., Liebisch, G., Luciani, M. F., Chimini, G., Kaminski, W.E. and Schmitz, G., 1999. Molecular cloning of the human ATP-binding cassette transporter 1 (hABC1): evidence for sterol-dependent regulation in macrophages. Biochemical and Biophysical Research Communications 257, 29-33.

  • Lee, J., Shirk, A., Oram, J.F., Lee, S.P. and Kuver, R., 2002. Polarized cholesterol and phospholipid efflux in cultured gall-bladder epithelial cells: evidence for an ABCA1-mediated pathway. Biochemical Journal 364, 475-484.

  • Linsel-Nitschke, P., Jehle, A. W., Shan, J., Cao, G., Bacic, D., Lan, D., Wang, N. and Tall, A.R., 2005. Potential role of ABCA7 in cellular lipid efflux to apoA-I. Journal of Lipid Research 46, 86-92.

  • Liu, Y. and Tang, C., 2012. Regulation of ABCA1 functions by signaling pathways. Biochimica et Biophysica Acta 1821, 522-529.

  • Mani, O., Korner, M., Ontsouka, C.E., Sorensen, M. T., Sejrsen, K., Bruckmaier, R.M. and Albrecht, C., 2011. Identification of ABCA1 and ABCG1 in milk fat globules and mammary cells - implications for milk cholesterol secretion. Journal of Dairy Science 94, 1265-1276.

  • Mani, O., Korner, M., Sorensen, M.T., Sejrsen, K., Wotzkow, C., Ontsouka, C.E., Friis, R.R., Bruckmaier, R.M. and Albrecht, C., 2010. Expression, localization, and functional model of cholesterol transporters in lactating and nonlactating mammary tissues of murine, bovine, and human origin. American Journal of Physiology-regulatory Integrative and Comparative Physiology 299, R642-654.

  • Mani, O., Sorensen, M.T., Sejrsen, K., Bruckmaier, R.M. and Albrecht, C., 2009. Differential expression and localization of lipid transporters in the bovine mammary gland during the pregnancy-lactation cycle. Journal of Dairy Science 92, 3744-3756.

  • Mather, I.H. and Keenan, T.W., 1998. Origin and secretion of milk lipids. Journal of Mammary Gland Biology and Neoplasia 3, 259-273.

  • McLean, L.R. and Phillips, M.C., 1981. Mechanism of cholesterol and phosphatidylcholine exchange or transfer between unilamellar vesicles. Biochemistry 20, 2893-2900.

  • Mesilati-Stahy, R., Mida, K. and Argov-Argaman, N., 2011. Size-dependent lipid content of bovine milk fat globule and membrane phospholipids. Journal of Agricultural and Food Chemistry 59, 7427-7435.

  • Mishkel, M.A., 1974. Neonatal plasma lipids as measured in cord blood. Canadian Medical Association Journal 111, 775-780.

  • Monks, J., Huey, P.U., Hanson, L., Eckel, R.H., Neville, M.C. and Gavigan, S., 2001. A lipoprotein-containing particle is transferred from the serum across the mammary epithelium into the milk of lactating mice. Journal of Lipid Research 42, 686-696.

  • Nagao, K., Takahashi, K., Azuma, Y., Takada, M., Kimura, Y., Matsuo, M., Kioka, N. and Ueda, K., 2012. ATP hydrolysis-dependent conformational changes in the extracellular domain of ABCA1 are associated with apoA-I binding. Journal of Lipid Research 53, 126-136.

  • Ontsouka, C.E., Bruckmaier, R.M. and Blum, J.W., 2003. Fractionized milk composition during removal of colostrum and mature milk. Journal of Dairy Science 86, 2005-2011.

  • Ontsouka, E.C., Huang, X., Stieger, B., Albrecht, C., 2013. Characteristics and functional relevance of apolipoprotein-A1 and cholesterol binding in mammary gland tissues and epithelial cells. PLoS ONE 8(7): e70407.

  • Owen, C.G., Martin, R.M., Whincup, P.H., Smith, G.D. and Cook, D.G., 2005. Effect of infant feeding on the risk of obesity across the life course: a quantitative review of published evidence. Pediatrics 115, 1367-1377.

  • Park, Y.W., Juarez, M., Ramos, M. and Haenlein, G.F.W., 2007. Physico-chemical characteristics of goat and sheep milk. Small Ruminant Research 68, 88-113.

  • Patton, S. and Jensen, R.G., 1975. Lipid metabolism and membrane functions of the mammary gland. Progress in the Chemistry of Fats and other Lipids 14, 163-277.

  • Pentchev, P.G., 2004. Niemann-Pick C research from mouse to gene. Biochimica et Biophysica Acta 1685, 3-7.

  • Picaud, J.C., Chapalain, V., Paineau, D., Zourabichvili, O., Bornet, F.R. and Duhamel, J.F., 2010. Incidence of infectious diseases in infants fed follow-on formula containing synbiotics: an observational study. Acta Paediatrica 99, 1695-1700.

  • Picciano, M.F., 2001. Representative values for constituents of human milk. Pediatric Clinics of North America 48, 263-264.

  • Reinhardt, T.A. and Lippolis, J.D., 2006. Bovine milk fat globule membrane proteome. Journal of Dairy Research 73, 406-416.

  • Rudnicka, A.R., Owen, C.G. and Strachan, D.P., 2007. The effect of breastfeeding on cardiorespiratory risk factors in adult life. Pediatrics 119, e1107-1115.

  • Schimanski, S., Wild, P.J., Treeck, O., Horn, F., Sigruener, A., Rudolph, C., Blaszyk, H., Klinkhammer-Schalke, M., Ortmann, O., Hartmann, A. and Schmitz, G., 2009. Expression of the lipid transporters ABCA3 and ABCA1 is diminished in human breast cancer tissue. Hormone and Metabolic Research 42, 102-109.

  • Stefulj, J., Panzenboeck, U., Becker, T., Hirschmugl, B., Schweinzer, C., Lang, I., Marsche, G., Sadjak, A., Lang, U., Desoye, G. and Wadsack, C., 2009. Human endothelial cells of the placental barrier efficiently deliver cholesterol to the fetal circulation via ABCA1 and ABCG1. Circulation Research 104, 600-608.

  • Takahashi, K., Kimura, Y., Nagata, K., Yamamoto, A., Matsuo, M. and Ueda, K., 2005. ABC proteins: key molecules for lipid homeostasis. Medical Molecular Morphology 38, 2-12.

  • Tang, W., Jia, L., Ma, Y., Xie, P., Haywood, J., Dawson, P. A., Li, J. and Yu, L., 2011. Ezetimibe restores biliary cholesterol excretion in mice expressing Niemann-Pick C1-Like 1 only in liver. Biochimica et Biophysica Acta 1811, 549-555.

  • Ueda, K., 2011. ABC proteins protect the human body and maintain optimal health. Bioscience Biotechnology and Biochemistry 75, 401-409.

  • Vanier, M. T. and Millat, G., 2003. Niemann-Pick disease type C. Clinical Genetics 64, 269-281.

  • Vaughan, A.M. and Oram, J.F., 2005. ABCG1 redistributes cell cholesterol to domains removable by high density lipoprotein but not by lipid-depleted apolipoproteins. The Journal of Biological Chemistry 280, 30150-30157.

  • Velamakanni, S., Wei, S., Janvilisri, T. and Van Veen, H., 2007. ABCG transporters: structure, substrate specificities and physiological roles: a brief overview. Journal of Bioenergetics and Biomembranes 39, 465-471.

  • Victora, C.G., Vaughan, J.P., Lombardi, C., Fuchs, S.M.C., Gigante, L.P., Smith, P.G., Nobre, L.C., Teixeira, A. M.B., Moreira, L.B. and Barros, F.C., 1987. Evidence for protection by breast-feeding against infant deaths from infectious-diseases in Brazil. Lancet 355, 319-322.

  • Viturro, E., Farke, C., Meyer, H.H. and Albrecht, C., 2006. Identification, sequence analysis and mRNA tissue distribution of the bovine sterol transporters ABCG5 and ABCG8. Journal of Dairy Science 89, 553-561.

  • Viturro, E., Koenning, M., Kroemer, A., Schlamberger, G., Wiedemann, S., Kaske, M. and Meyer, H.H., 2009. Cholesterol synthesis in the lactating cow: induced expression of candidate genes. Journal of Steroid Biochemistry and Molecular Biology 115, 62-67.

  • Wang, N., Lan, D., Gerbod-Giannone, M., Linsel-Nitschke, P., Jehle, A.W., Chen, W., Martinez, L.O. and Tall, A.R., 2003. ATP-binding cassette transporter A7 (ABCA7) binds apolipoprotein A-I and mediates cellular phospholipid but not cholesterol efflux. Journal of Biological Chemistry 278, 42906-42912.

  • Wang, Y., Tong, J., Li, S., Zhang, R., Chen, L., Zheng, M., Wang, M., Liu, G., Dai, Y., Zhao, Y. and Li, N., 2011. Over-expression of human lipoprotein lipase in mouse mammary glands leads to reduction of milk triglyceride and delayed growth of suckling pups. PLoS One 6, e20895.

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