Docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6) are deposited in large amounts in membrane phospholipids of the developing central nervous system (CNS). High levels of 22:6n-3 are found in synaptic terminals and retina, and are important for normal visual development and function. 20:4n-6 and22:6n-3 are supplied in human milk. In contrast, infants fed formula rely completely on endogenous synthesis of 20:4n-6 and 22:6n-3 from linoleic (18:2n-6) and a-linolenic (18:3n-3) acid, respectively. Levels of 22:6n-3 in the blood lipids of infants fed formula are lower than in infants fed human milk. Concern over the supply of 22:6n-3 led to clinical trials in which premature infants were fed formulas containing fish oils as a source of 22:6n-3. Piglets, which have a similar lipid metabolism and perinatal timing of the brain growth spurt to humans, have a lower percentage of 22:6n-3 in blood, liver and CNS tissues when fed formula with 30% of fatty acids as18:2n-6 and 0.8% 18:3n-3, compared to sow milk. It was hypothesized that the low blood and tissue 22:6n-3 in formula-fed piglets was due to inappropriate quantities and/or ratios of dietary 18:2n-6 and 18:3n-3 limiting the synthesis of 22:6n-3. Thus, the main objectives of this thesis were to determine. (1) if 22:6n-3 is an essential dietary nutrient for the term gestation piglet, (2) if appropriate quantities and ratios of 18:2n-6 and 18:3n-3 in formula will support CNS membrane accretion of 20:4n-6 and 22:6n-3, comparable to piglets fed varying amounts of 22:6n-3 in natural milk, and (3) if lower blood phospholipid 22:6n-3 consistently reflects reduced 22:6n-3 in the CNS.
Initial studies (Experiment I) showed that formula with 4% 18:3n-3 supported a similar percentage of22:6n-3 in piglet liver and CNS membrane lipids to sow milk, but was associated with lower brain weight. Deposition of 22:6n-3 in brain was influenced by the formula 18:3n-3 content. The 18:2n-6:18:3n-3 ratio (22:1and 37:1) seemed to be important, however, when formulas contained 1% 18:3n-3. Low levels of fish oil in formula, similar to those used in clinical trials, were effective in supplying 22:6n-3 to the developing piglet brain (Experiment II). The efficacy of 18:3n-3 in supporting the deposition of 22:6n-3 in the brain was estimated to be at least 20% that of dietary 20:5n-3 plus 22:6n-3. With increasing dietary fish oil, however, levels of eicosapentaenoic acid (20:5n-3) increased and 20:4n-6decreased in plasma, liver and retina, but not brain (Experiment III). This suggests regulatory mechanisms may exist to maintain relatively constant levels of 20:4n-6 and 20:5n-3 in brain. Milk 22:6n-3 varies with maternal intake of 22:6n-3. The effect of milk 22:6n-3 content was studied in piglets fed milk with 0.1% or 1.5% 22:6n-3 obtained from sows fed usual pig diets containing vegetable fats without or with fish oil, respectively (Experiment IV). Consumption of 1.5 vs 0.1% 22:6n-3 from sow milk resulted in 300% higher 22:6n-3 in liver and blood phospholipids and 11% higher 22:6n-3 in cerebrum of nursing piglets. Despite similar milk 20:4n-6, the % 20:4n-6 in tissues other than the brain was lower in piglets fed high22:6n-3 sow milk. Thus, high intakes of n-3 fatty acids decrease 20:4n-6 in piglet liver and blood lipids. The blood phospholipid % 22:6n-3 in piglets fed formulas containing 18:2n-6 and 18:3n-3 but not their long-chain derivatives, was lower than in piglets fed 22:6n-3 in natural milk, consistent with published findings in formula-fed infants. However, in contrast to circulating lipids, formulas with 4% 18:3n-3 maintained similar levels of 22:6n-3in the piglet CNS compared to milk. These studies show that blood phospholipid 22:6n-3 and 20:4n-6 are not specific indices of effects in CNS lipids. This thesis has shown (1) 22:6n-3 is not essential in the diet of the term piglet, if adequate 18:3n-3 is given, (2) fish oils are an effective source of 22:6n-3 for deposition in the developing brain, (3) high dietary n-3fatty acids interfere with 20:4n-6 metabolism, and (4) blood lipid 20:4n-6 and 22:6n-3 do not accurately reflect CNS fatty acids.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:BVAU.2429/2373 |
| Date | 11 1900 |
| Creators | Arbuckle, Lucille D. |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Relation | UBC Retrospective Theses Digitization Project [http://www.library.ubc.ca/archives/retro_theses/] |
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