Pilot Study on Mammary Expression of Novel Desaturases

Summary

Principal Investigator: Alison L Van Eenennaam
Abstract: Vertebrates lack the delta-12 and delta-15 fatty acid desaturases responsible for producing the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs), respectively, and hence these PUFAs are essential components of vertebrate diets. Milk fatty acid composition in monogastric mammals is reflective of the dietary fatty acid composition. The ratio of omega-6 to omega-3 fatty acids present in the diet of industrial societies has increased as a result of the greater consumption of vegetable oils containing omega-6 fatty acids and reduced consumption of foods rich in the omega-3 fatty acids. Results of some studies have indicated that high levels of omega-6 and low levels of omega-3 PUFAs in the maternal diet during gestation and the nursing period may metabolically "imprint" the postnate for excessive adipogenesis with a subsequent propensity towards childhood obesity. To investigate this theory further, transgenic mice carrying the Caenorhabditis elegans delta-12 or delta-15 fatty acid desaturase gene under the control of a lactation-specific promoter were produced. We hypothesize that lactating delta-12 transgenic females will be able to produce milk containing linoleic acid (18:2, omega-6) derived from dietary oleic acid (18:1), and delta-15 transgenic females will be able to produce milk containing alpha-linolenic acid (18:3n3, omega-3) from linoleic acid. These desaturase transgenic mice will offer a unique opportunity to dissociate metabolic imprinting effects resulting from dietary fatty acid composition during fetal development from those that result from the postparturitional dietary environment. The specific aims of this pilot project are to establish and characterize the delta-12 desaturase, delta-15 desaturase, and delta-12 desaturase/delta-15 desaturase double transgenic mouse lines, and determine the milk fatty acid composition phenotype seen with each genotype in response to altering dietary fatty acid compositions. Milk will be collected from lactating females fed either a standard diet (moderate levels of oleic acid and linoleic acid) or a high oleic acid diet. The actual amounts of LA and ALA in milk derived from transgenic mice, the omega-6 to omega-3 ratio, and the magnitude of milk fatty acid composition changes that can be effected by changing the maternal dietary fatty acid composition will provide the background information necessary to determine the types of nutritional studies that can be proposed with this unique model system.
Funding Period: 2004-08-01 - 2007-07-31
more information: NIH RePORT

Top Publications

  1. ncbi Endogenous production of n-3 and n-6 fatty acids in mammalian cells
    K C Morimoto
    Department of Animal Science, University of California, Davis, CA 95616, USA
    J Dairy Sci 88:1142-6. 2005
  2. pmc Reproductive abnormalities in mice expressing omega-3 fatty acid desaturase in their mammary glands
    William E Pohlmeier
    Department of Animal Science, University of California, Davis, CA 95616, USA
    Transgenic Res 20:283-92. 2011
  3. ncbi Endogenous production and elevated levels of long-chain n-3 fatty acids in the milk of transgenic mice
    B T Kao
    Department of Animal Science, University of California, Davis 95616, USA
    J Dairy Sci 89:3195-201. 2006
  4. ncbi Mice raised on milk transgenically enriched with n-3 PUFA have increased brain docosahexaenoic acid
    Beth T Kao
    Department of Animal Science, University of California, Davis, CA 95616, USA
    Lipids 41:543-9. 2006
  5. ncbi Neonatal growth rate and development of mice raised on milk transgenically enriched with omega-3 fatty acids
    Kathleen D Bongiovanni
    Department of Animal Science, University of California Davis, Davis, California 95616, USA
    Pediatr Res 62:412-6. 2007
  6. ncbi Manipulation of milk fat composition through transgenesis
    A L Van Eenennaam
    Department of Animal Science, University of California, Davis 95616 8521, USA
    Adv Exp Med Biol 606:345-56. 2008

Scientific Experts

  • Alison L Van Eenennaam
  • William E Pohlmeier
  • Kathleen D Bongiovanni
  • Edward J DePeters
  • Beth T Kao
  • B T Kao
  • E J DePeters
  • K C Morimoto
  • Russell C Hovey
  • K A Lewis
  • J F Medrano

Detail Information

Publications6

  1. ncbi Endogenous production of n-3 and n-6 fatty acids in mammalian cells
    K C Morimoto
    Department of Animal Science, University of California, Davis, CA 95616, USA
    J Dairy Sci 88:1142-6. 2005
    ....
  2. pmc Reproductive abnormalities in mice expressing omega-3 fatty acid desaturase in their mammary glands
    William E Pohlmeier
    Department of Animal Science, University of California, Davis, CA 95616, USA
    Transgenic Res 20:283-92. 2011
    ....
  3. ncbi Endogenous production and elevated levels of long-chain n-3 fatty acids in the milk of transgenic mice
    B T Kao
    Department of Animal Science, University of California, Davis 95616, USA
    J Dairy Sci 89:3195-201. 2006
    ..Increasing the proportion of n-3 PUFA in milk fat would help to improve the nutritional composition of an important component of the North American diet...
  4. ncbi Mice raised on milk transgenically enriched with n-3 PUFA have increased brain docosahexaenoic acid
    Beth T Kao
    Department of Animal Science, University of California, Davis, CA 95616, USA
    Lipids 41:543-9. 2006
    ....
  5. ncbi Neonatal growth rate and development of mice raised on milk transgenically enriched with omega-3 fatty acids
    Kathleen D Bongiovanni
    Department of Animal Science, University of California Davis, Davis, California 95616, USA
    Pediatr Res 62:412-6. 2007
    ..This transgenic model enables the provision of a high n-3 PUFA lactational environment independent of maternal diet or gestational FA status...
  6. ncbi Manipulation of milk fat composition through transgenesis
    A L Van Eenennaam
    Department of Animal Science, University of California, Davis 95616 8521, USA
    Adv Exp Med Biol 606:345-56. 2008