Mice raised on milk transgenically enriched with n−3 PUFA have increased brain docosahexaenoic acid

Abstract

The brain contains high levels of the long-chain n-3 FA DHA (22:6n-3), mainly in the gray matter and synaptosomes. Adequate intake of DHA is crucial for optimal nervous system function, particularly in infants. Supplementation of infant formulas with DHA at levels similar to human breast milk is recommended for biochemical and functional benefits to neonates. We generated transgenic mice that produce elevated levels of n-3 PUFA in their milk by expressing the Caenorhabditis elegans n-3 FA desaturase under the control of a lactation-induced goat beta-casein promoter. To examine the postnatal effects of consuming the n-3-enriched milk, we compared the growth and brain and plasma FA composition of mouse pups raised on milk from transgenic dams with those observed for pups raised on milk from nontransgenic dams. A significant decrease in arachidonic acid (ARA, 20:4n-6) and concomitant increases in n-3 PUFA were observed in the phospholipid fraction of transgenic mouse milk. The n-6:n-3 FA ratios were 4.7 and 34.5 for the transgenic and control milk phospholipid fractions, respectively. DHA and DPA (22:5n-6) comprised 15.1% and 2.8% of brain FA from weanling mice nursed on transgenic dams, as compared with 6.9% and 9.2% for weanling mice nursed on control dams, respectively. This transgenic mouse model offers a unique approach to disassociate the effects and fetal programming resulting from a high n-6:n-3 FA ratio gestational environment from the postnatal nutritional effects of providing milk with differing n-6:n-3 FA ratios.

Neonatal Growth Rate and Development of Mice Raised on Milk Transgenically Enriched With Omega-3 Fatty Acids

“…The FA composition of this diet and the milk produced by wildtype and transgenic dams consuming it was previously reported (22). The FA breakdown of the experimental diet was 3.2% C18:0, 17.8% C18:1, 69.2% C18:2n-6, 0.17% C18:3n-3; 0.0% C20:4n-6, and C22:6n-3, and the n-6:n-3 ratio was 407.…”

“…The light cycle was 0700 -2100 h (14-h light cycle). A single pup from each litter was euthanized at PND 22 via carbon dioxide asphyxiation and the brain removed and analyzed for FA composition (22). Toe samples for genotyping were also taken from all pups at the completion of the experiment (21).…”

“…The object novelty preference test was conducted on the mice immediately after weaning (PND [22][23]. No treatment effects were observed for the duration, frequency, or percentage of time spent in the novel or familiar half of the area, in the immediate area of the novel or familiar object, or in sniffing the novel or familiar object (data not shown).…”

“…This transgene was found to be expressed in the lactating mammary gland but not the brain of animals carrying the transgene, and the brain lipid profile of pups raised on transgenic dams showed a significant increase in DHA and EPA levels compared with controls (22). This mouse model is useful for the evaluation of the role of n-3 PUFAs in cognitive development of neonates because it allows dietary manipulation of n-3 PUFAs in the gestational environment to occur independently of the n-3 PUFA sufficiency of the lactational environment.…”

The use of genetic engineering techniques to improve the lipid composition in meat, milk and fish products: a review

“…The milk of modified mice was characterised by improved lipid composition, that is it contained significantly increased levels of n-3 PUFAs, as well as decreased levels of n-6 PUFAs and a reduced n-6/n-3 PUFA ratio. The authors also evaluated the postnatal influences of n-3 PUFA-enriched milk, by analysing the growth, as well as brain and plasma lipid composition, of mouse pups raised on milk from transgenic mice (Kao et al, 2006a). There were no significant differences in the weights of the pups, but weanlings raised on milk from transgenic dams had increased concentrations of EPA, DPA and DHA in plasma lipids, and ALA, DPA and DHA in brain lipids.…”