Over-Expression of Human Lipoprotein Lipase in Mouse Mammary Glands Leads to Reduction of Milk Triglyceride and Delayed Growth of Suckling Pups

Background The mammary gland is a conserved site of lipoprotein lipase expression across species and lipoprotein lipase attachment to the luminal surface of mammary gland vascular endothelial cells has been implicated in the direction of circulating triglycerides into milk synthesis during lactation. Principal Findings Here we report generation of transgenic mice harboring a human lipoprotein lipase gene driven by a mammary gland-specific promoter. Lipoprotein lipase levels in transgenic milk was raised to 0.16 mg/ml, corresponding to an activity of 8772.95 mU/ml. High lipoprotein lipase activity led to a significant reduction of triglyceride concentration in milk, but other components were largely unchanged. Normal pups fed with transgenic milk showed inferior growth performances compared to those fed with normal milk. Conclusion Our study suggests a possibility to reduce the triglyceride content of cow milk using transgenic technology.

[1]  S. Young,et al.  GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries. , 2010, Cell metabolism.

[2]  M. Hayden,et al.  Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia , 2010, Journal of Lipid Research.

[3]  Ran Zhang,et al.  Functional recombinant human anti-HAV antibody expressed in milk of transgenic mice , 2009, Transgenic Research.

[4]  M. C. Rudolph,et al.  Metabolic regulation in the lactating mammary gland: a lipid synthesizing machine. , 2007, Physiological genomics.

[5]  Fredrik Karpe,et al.  Preferential Uptake of Dietary Fatty Acids in Adipose Tissue and Muscle in the Postprandial Period , 2007, Diabetes.

[6]  Ning Li,et al.  Maternally Derived Recombinant Human Anti-Hantavirus Monoclonal Antibodies Are Transferred to Mouse Offspring during Lactation and Neutralize Virus In Vitro , 2006, Journal of Virology.

[7]  H. Steinhart,et al.  Dietary conjugated linoleic acids lower the triacylglycerol concentration in the milk of lactating rats and impair the growth and increase the mortality of their suckling pups. , 2004, The Journal of nutrition.

[8]  W. Bowen,et al.  Lipoprotein lipase activity and its relationship to high milk fat transfer during lactation in grey seals , 2004, Journal of Comparative Physiology B.

[9]  A Ferlay,et al.  A review of nutritional and physiological factors affecting goat milk lipid synthesis and lipolysis. , 2003, Journal of dairy science.

[10]  G. Shulman,et al.  Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Eckel,et al.  Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance. , 2001, Diabetes.

[12]  R. Zechner,et al.  Induced Mutant Mice Expressing Lipoprotein Lipase Exclusively in Muscle Have Subnormal Triglycerides yet Reduced High Density Lipoprotein Cholesterol Levels in Plasma* , 1997, The Journal of Biological Chemistry.

[13]  M. Neville,et al.  Regulation of milk lipid secretion and composition. , 1997, Annual review of nutrition.

[14]  H. Radner,et al.  Muscle-specific overexpression of human lipoprotein lipase in mice causes increased intracellular free fatty acids and induction of peroxisomal enzymes. , 1997, Biochimie.

[15]  R. Stollberger,et al.  Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice. , 1995, The Journal of clinical investigation.

[16]  R. Potenz,et al.  Transgenic mice expressing human lipoprotein lipase driven by the mouse metallothionein promoter. A phenotype associated with increased perinatal mortality and reduced plasma very low density lipoprotein of normal size. , 1994, The Journal of biological chemistry.

[17]  A. Lusis,et al.  Alteration of lipid profiles in plasma of transgenic mice expressing human lipoprotein lipase. , 1994, The Journal of biological chemistry.

[18]  S. Coppack,et al.  Regulation of fatty acid movement in human adipose tissue in the postabsorptive-to-postprandial transition. , 1994, The American journal of physiology.

[19]  R. Eckel,et al.  Regulation of lipoprotein lipase activity and mRNA in the mammary gland of the lactating mouse. , 1994, The Biochemical journal.

[20]  Y. Yazaki,et al.  Overexpression of human lipoprotein lipase in transgenic mice. Resistance to diet-induced hypertriglyceridemia and hypercholesterolemia. , 1993, The Journal of biological chemistry.

[21]  D. Severson,et al.  Regulation of the synthesis, processing and translocation of lipoprotein lipase. , 1992, The Biochemical journal.

[22]  J. Hartsuck,et al.  Structure and functional properties of lipoprotein lipase. , 1992, Biochimica et biophysica acta.

[23]  R. Eckel,et al.  Distribution and source of lipoprotein lipase in mouse mammary gland. , 1991, Journal of lipid research.

[24]  Y. Chilliard,et al.  Characteristics of Lipolytic System in Goat Milk , 1984 .

[25]  A Cryer,et al.  Tissue lipoprotein lipase activity and its action in lipoprotein metabolism. , 1981, The International journal of biochemistry.

[26]  P. Nilsson-ehle,et al.  A stable, radioactive substrate emulsion for assay of lipoprotein lipase. , 1976, Journal of lipid research.

[27]  M. Hamosh,et al.  Lipoprotein lipase activity of adipose and mammary tissue and plasma triglyceride in pregnant and lactating rats. , 1970, Biochimica et biophysica acta.