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.