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.

Dietary fatty acid (FA) composition and energy restriction (ER) independently affect serum leptin levels; however it is not known whether this correlates with changes in obese (ob) gene expression. Herein, we assessed whether dietary FA composition and ER influence white adipose tissue (WAT) ob mRNA by Northern analysis. Animals consumed diets containing tallow (BT), safflower oil (SO) or fish oil (FO) ad libitum or at 60% ad libitum intakes. Serum leptin values were not different between levels of energy intake. ER decreased weight gain and WAT weights, which positively correlated with serum leptin values. WAT ob mRNA levels were in the rank order: FO > SO > BT in depots of all groups with ER showing a lower level of ob mRNA. Data show similarity in ob mRNA levels between depots with discordance in circulating leptin levels. These data suggest that energy restriction exerts greater control over leptin production than dietary fat source.

Thesis (Ph.D.)--Aberdeen University, 2009. / Title from web page (viewed on Dec. 8, 2009). Includes bibliographical references.

Microbiota are present in large numbers and as a diverse population within the gastrointestinal tract. There are approximately 400 different species of microbiota which may be beneficial, harmful or both, but each play an important role in the regulation and modulation of the hosts’ bowel processes (McOrist et al. 2008; Dethlefsen et al. 2008). Many of these colon microbiota allow for saccharolytic fermentation of non-digestible dietary fibres and carbohydrates into by-products and intermediates, followed by a subsequent conversion into short chain fatty acids (SCFAs) (mainly n-butyric acid, propionic acid and acetic acid) each of which play an important role in maintaining colon homeostasis (Topping & Clifton 2001). A balance of ‘good’ microbiota (e.g., Bacteroides spp./ Bifidobacteria spp.) and ‘bad’ microbiota (e.g., Veilonellae) and the optimal production of various SCFAs within the gut could possibly allow for proper functioning of the large intestine and assist in decreasing the onset of various colonic disorders such as Irritable Bowel Syndrome (IBS). The sample group for the study consists of male and female patients, with an average age of 40 to 50 years old, whom of which have been diagnosed with either constipation IBS (C-IBS) or diarrhoea IBS (D-IBS) via the Rome III criteria system for IBS diagnosis. DNA and SCFA extractions were optimised for human stool, colonic fluid and tissue biopsy sample obtained from the aforementioned patients. Optimization steps allowed for starting material with high analysis integrity. Different methods of microbiota analysis, such as ARISA, were investigated; however, real-time qPCR was selected as the best method to identify and quantify specific microbiota. Extracted SCFAs were separated via gas chromatography and identified and quantified via Mass Spectrometry. Significant changes in microbial content and SCFA profiles were found to be associated with healthy and IBS patients. Results obtained would however be influenced by external factors typical of clinical studies of this nature. This study allows for opportunities for future research into understanding IBS.

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. / Land and Food Systems, Faculty of / Graduate

No description available.

Preliminary data from studies in rodents suggests time-dependent associations between dietary LC n-3 PUFA and hepatic levels of the enzyme soluble epoxide hydrolase (sEH), which regulates the metabolism and availability of epoxyeicosatrienoic acids (EET).  EET are cytochrome P450 epoxygenase products of arachidonic acid associated with  lower blood pressure, decreased inflammatory response and inhibition of blood coagulation. To further investigate the association between LC n-3 PUFA and sEH, ApoE^-/^- mice were fed a high-fat high-cholesterol diet supplemented with either fish oil (EPA + DHA) or DHA or HOSF (all 2% w/w) for 10 weeks and livers and aortic roots were collected on day 2 and weeks 1, 2, 4 and 10.  Proteomics analysis showed an overall decreasing effect of fish oil (but not DHA) supplementation on hepatic protein levels of sEH compared to the control throughout the intervention period (<i>P</i> &lt; 0.05).  Neither fish oil nor DHA intervention affected atherosclerotic plaque size in the aortic root. We also examined how dietary supplementation with 1 g/day EPA or 1 g/day DHA for 10 days affects platelet sEH levels and platelet aggregation compared to 1 g/day HOSF (control) in healthy volunteers in a double-blind, placebo-controlled, cross-over trial.  We found that DHA decreased platelet aggregation by 10% (<i>P =</i> 0.04) and EPA also inhibited ADP (5 μM)-induced platelet aggregation by 14% compared to the control group but this effect did not reach statistical significance due to high variability between subjects.  EPA decreased platelet sEH levels by 25% (not significant), whereas DHA had no effect.  We also attempted to optimize a method for measuring EET in plasma and platelets.  However, the rapid conversion of EET to other compounds and their low concentration in tissues prevented us from optimizing such a method within the time limits of the project.

My thesis research has examined the fatty acid composition of serum triacylglycerol, phospholipid and cholesterol ester in 2793 participants who took part in the 1997 National Nutrition Survey - a national population-based survey of New Zealand adolescents and adults aged or [greater than or equal to]̲15 y. Differences in serum fatty acids by sex, age, ethnicity, body mass index and smoking - independent of dietary fat intake - were determined. Serum fatty acids were used as biomarkers of saturated and polyunsaturated fat intake to predict population serum total cholesterol concentrations. The association between n-3 long-chain polyunsaturated fatty acids in serum phospholipid and mental and physical wellbeing, as assessed by the short form-36, was determined. Serum fatty acids have been used as biological markers of fat intake and to predict the risk of disease. The fatty acid composition of serum triacylglycerol, phospholipid and cholesterol ester is subject to alteration by dietary fat but overall, is largely controlled by metabolic enzymes. Non-dietary variables - sex, age, body mass index or cigarette smoking - may influence the activity of these enzymes, which will subsequently alter the fatty acid composition but the extent to which these affect serum fatty acid composition in the general population is poorly understood. Our results showed that the proportion of docosahexaenoic acid in serum phospholipid and cholesterol ester was significantly greater in women by 0.15 and 0.02 mol%, respectively in comparison to men whereas, the proportion of eicosapentaenoic acid was significantly greater in men by 0.08 and 0.1 mol%, respectively, after adjusting for age, ethnicity, body mass index and smoking. A number of differences in the proportion of palmitoleic acid in serum triacylglycerol, phospholipid and cholesterol ester were detected; palmitoleic acid increased across the age categories in women (15-24, 25-44, 45-64 65+ y), was higher in women compared to men, New Zealand Europeans compared to New Zealand Maori and Pacific People, those with a body mass index or [greater than or equal to] 30 kg/m� compared to those with a body mass index < 25 kg/m� and in current smokers in comparison to non-smokers. In women, there was an inverse trend in the proportion of linoleic acid in serum phospholipid and cholesterol ester across the age categories. The proportion of linoleic acid in serum triacylglycerol, phospholipid and cholesterol ester was lower in smokers by 2.19, 1.04 and 0.75 mol%, respectively in comparison to non-smokers. None of these differences could be explained by a difference in dietary fat intake. Consequently, sex appears to affect the metabolism of n-3 long-chain polyunsaturated fatty acids independent of dietary fat intake and metabolic differences associated with age, body mass index and smoking may be at play for a number of other serum fatty acids notably, palmitoleic and linoleic acids. Evidence for a role of dietary fat as a predictor of serum cholesterol concentrations in the general population is conflicting. On one hand, results from cholesterol-lowering dietary intervention trials show unequivocally that decreasing saturated fat intake produces a meaningful reduction in serum cholesterol concentrations. On the other hand, the results of large observational studies show little association between saturated fat intake and cholesterol concentrations. The lack of association in the latter studies may result from errors in dietary assessment and therefore, using serum fatty acids as biomarkers of fat intake may overcome the limitations associated with typical dietary assessment techniques. Participants were divided into quintiles of increasing proportion of serum fatty acids. Each one SD increase in the myristic acid composition of serum cholesterol ester, triacylglycerol and phospholipid was associated with an increase in cholesterol of 0.19, 0.10 and 0.13 mmol/L, respectively after adjusting for confounding variables. The difference in cholesterol concentrations between those categorised into the highest and lowest quintiles of serum cholesterol ester myristate was 0.48 mmol/L. A one SD increase in the linoleic acid composition of serum cholesterol ester, triacylglycerol and phospholipid corresponded to a decrease in cholesterol of 0.07, 0.05 and 0.07 mmol/L, respectively. The difference in cholesterol concentrations between the 1st and 5th quintiles of serum cholesterol linoleate was 0.18 mmol/L. Intake of saturated and polyunsaturated fats, as measured using serum fatty acids, are important determinants of cholesterol concentrations in New Zealanders. It has been hypothesised that a lower intake of n-3 long-chain polyunsaturated fatty acids, largely of marine origin, is implicated in the aetiology of depressive disorder. Results from the majority of observational studies have shown that depressed participants have a lower proportion of eicosapentaenoic or docosahexaenoic acid in phospholipids compared to controls but evidence for an improvement in depressive symptoms after supplementation with n-3 long-chain polyunsaturated fatty acids is conflicting. There is little known about the role that n-3 long-chain polyunsaturated fatty acids may have as predictors of mental wellbeing in the general population. Participants were categorised into quintiles of increasing n-3 long-chain polyunsaturated fatty acids in serum phospholipid. There was no significant trend in self-reported mental wellbeing - the mental component score - across the quintiles of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids or the sum of these three fatty acids after adjusting for confounding variables. There was a significant trend in the mental component score across the quintiles of the ratio of eicosapentaenoic/arachidonic acid; the difference between the highest and the lowest quintile was 6.6 points. There were significant positive trends in self-reported physical health - the physical component score - across the quintiles of eicosapentaenoic and docosapentaenoic acids as well as the ratio of eicosapentaenoic/arachidonic acid ratio; the difference between the 1st and 5th quintiles were 8.6, 6.0 and 8.9 points, respectively. Overall, there appears to be little association between the n-3 long-chain polyunsaturated fatty acid composition of serum phospholipid and self-reported mental health in a population of low fish consumers; however, the proportion of n-3 long-chain polyunsaturated fatty acids may be an important predictor of physical wellbeing in New Zealanders.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 105-117).

published_or_final_version / Botany / Master / Master of Philosophy