Developmental maturation of hepatic n-3 polyunsaturated fatty acid metabolism: Supply of docosahexaenoic acid to retina and brain

Abstract

Docasahexaenoic acid is an essential fatty acid enriched in lipids of photoreceptor, synaptic, and nerve growth cone membranes. [ 3H]docosahexaenoic acid was intraperitoneally injected in 5-day-old and 14-day-old mouse pups, and the labeling time course was followed in liver, plasma, brain, and retina for 72 hours. The liver of 5-day-old mice displayed higher content and labeling of triacylglycerols, lower content of phospholipids, and a more avid uptake of [ 3H]docosahexaenoic acid as compared with 14-day-old mice. Maximal [ 3H]docosahexaenoic acid labeling in the liver was observed 2 hr postinjection and decreased thereafter as [ 3H]docosahexaenoic acid accumulated in brain and retina. The most efficient [ 3H]docosahexaenoic acid accumulation in retina and brain occurred with 14-day-old pups and correlated with a higher labeling and a long half-life of [ 3H]docosahexaenoic acid phospholipids in liver (35 hr for 5-day-olds and 54 hr for 14-day-olds) and plasma (42 hr for 5 day-olds and 68 hr for 14-day-olds). As a function of time, the labeling profile in plasma lipids followed that of liver. A significant amount of total plasma decosahexaenoic acid was found esterified into cholesterol esters, while decosahexaenoic acid-phospholipids accounted for 60 to 70% at both ages. Docosahexaenoic acid cholesterol ester may also be a carrier of docosahexaenoic acid to neural tissues after synthesis in the liver and/or in high density lipoproteins from a liver-derived docosahexaenoic acid-phosphatidylcholine pool. Both cholesterol and docosahexaenoic acid are needed for neural membrane biogenesis. Collectively, these data indicate that the metabolism of docosahexaenoic acid by liver and the uptake and esterification of docosahexaenoic acid into hepatic lipids and its subsequent appearance in the plasma are developmentally regulated and under control by the liver. The esterification of docosahexaenoic acid into phospholipids and the increased half-life of [ 3H]docosahexaenoic acid-phospholipids in plasma may be salient factors modulating efficient docosahexaenoic acid delivery to the central nervous system.