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. ? ?
