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This Ph.D. dissertation presents results that shed light on whether there is an association between dietary intake and depressive disorder, feelings of sadness, or thoughts of death. This question is investigated in the context of a secondary data analysis using cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. Subjects in this study were identified as a subpopulation of the NHANES survey that completed the Composite International Diagnostic Interview questionnaire for major depression. The presence of depression may lead to a decline in dietary intake and nutritional status. Conversely, poor dietary intake may have a role in the etiology of depression. Specifically, depression is associated with lower plasma, erythrocyte, phospholipid, and adipose tissue omega-3 fatty acids. Little is known about the comprehensive dietary intake of those with depression or depressive symptoms. Initially, comparisons of the dietary profile between those with and without depression or depressive symptoms were investigated. Secondly, analysis was done to determine the relationship between dietary omega-3 fatty acids and depression or depressive symptoms. Lastly, to clarify the relationship between diet and depression, misreporting of dietary energy intake was evaluated.No significant differences in the dietary profile or nutritional biochemistries were found between the altered mood and normal mood groups. No significant differences were found in dietary omega-3 fatty acids between the depressed and non-depressed groups, even after adjusting for confounding variables. Misreporting of energy intake was not significantly associated with altered mood status and remained non-significant after adjusting for confounding variables. In both groups, a significant decreasing trend in the ratio of energy intake to estimated basal metabolic rate (EI:BMRest) was found as body mass index increased.Based on dietary intake alone, the relationship between depression and specific nutrients may not be apparent. Dietary intake among those with depression and depressive symptoms appears to be adequate, but adequacy may not be sufficient as a route for prevention or management of depression. Further investigation of diet and depression ought to measure diet, including nutrition supplements, and biochemical levels of nutrients from a broader age range of adults and children and those with comorbid illnesses.

The negative health effects of trans fatty acids from hydrogenated fats on plasma lipid profile have been well documented. However, the mechanisms responsible for these changes remain to be elucidated. Hence the overall objective of the thesis was to examine the effect of consuming different forms of hydrogenated fats on cholesterol and triglyceride metabolism, specifically fractional and absolute synthesis rates of free (FSR-FC and ASR-FC) and esterified (FSR-CE, AER and ER) cholesterol, and the functioning of the ASP pathway. In addition, validation of the newer deuterium incorporation (DI) method for measurement of endogenous cholesterol biosynthesis against the cholesterol precursor assessment approach was also performed. Fourteen moderately hypercholesterolemic (LDL-C ≥ 130 mg.dl-1) postmenopausal women (65--71yrs) participated in this study. Subjects consumed, in random order, each of 6 diets for 5 week periods, separated by washout periods ranging from 2 to 4 weeks in duration. The experimental diets included a baseline (BL) diet (39% kcal fat) and 5 reduced fat diets (30% kcal) where 2/3rd of the fat was either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), high trans stick (SM) margarines, or butter (BT). Results obtained from the series of analyses performed demonstrate that: (i) the DI method and levels of some cholesterol precursors correspond as methods for the study of in vivo cholesterol biosynthesis in humans; (ii) elevations in endogenous cholesterol synthesis (FSR-FC and ASR-FC) are not responsible for the increase in circulating cholesterol levels seen after consumption of the high trans SM, and high SFA rich BT and BL diets; (iii) suppression of cholesterol esterification rates on the SM diet may account for the decreased HDL-C levels observed on this diet and finally; (iv) dysfunction of the ASP pathway, with lower ASP and higher FFA levels could be responsible for the higher secretion of hepatic B 100 particles. In conc

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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.

The key defects characteristic of hyperglycemia in T2D include increased hepatic glucose production, a diminution of insulin secretion, and an absolute impairment in peripheral insulin action. The objective of my thesis was to investigate the molecular mechanisms leading to fatty acid induced β-cell dysfunction and determine the role of a novel transcriptional coregulator in the regulation of hepatic glucose homeostasis. The first part of my work focused on the chronic effects of fatty acids on human pancreatic β-cell function. Using microarray technology I established an important role for fatty acids in the pathogenesis of β-cell dysfunction. Accordingly chronic exposure of islets to oleate resulted in a significant reduction in glucose-stimulated insulin secretion and to an increase in the rate of reactive oxygen species generation. Additionally, pre-treatment of human islets with oleate led to a significant increase in the rate of oxidation of this fatty acid and to a significant decrease in glucose oxidation. My data indicate that chronic exposure of human islets to fatty acids activates inflammatory and metabolic pathways that lead to oxidative stress. In addition, the first part of my work demonstrated that fatty acids induce oxidative stress in vitro an effect that is preventable to a large extent by the use of antioxidants. In this setting and recapitulating the human islet data, fatty acids are causally linked to impaired insulin secretion, and the induction of oxidative stress. Our report demonstrated that oxidative stress plays a key role in the decrease in β-cell function induced by chronic lipotoxicity. My work also demonstrated that fatty acids are causally linked to the induction of endoplasmic reticulum stress in human islets. Finally, in the second part of my work I provide novel evidence for the role of PHIP in the regulation of hepatic gluconeogenesis. My work is the first to demonstrate that PHIP suppresses hepatic gluconeogenesis in vitro and in vivo. PHIP is amongst the few proteins that have ever been reported to suppress gluconeogenesis to date. PHIP thus represents a novel target for pharmaceutical intervention of diabetes and the suppression of hepatic glucose production.

Diet plays an important role in the development of chronic metabolic diseases (diabetes, obesity, cardiovascular disease) and as dietary fat consumption has increased, so has the incidence of these disorders. Metabolic syndrome, a clustering of risk factors that includes central obesity, increased plasma triacylglycerol (TG), elevated fasting glucose and glucose intolerance is perhaps the most notorious and aggressive. Animal and human studies indicate that bioactive fatty acids can influence cellular energy metabolism. Using susceptible rodent models (apoE-/- and LDLr-/- mice and Syrian Golden hamsters) this project investigated whether supplementation of a western type diet (WD) with bioactive fatty acids could improve hepatic lipid metabolism, plasma lipoprotein profiles or liver markers of lipogenesis. In mice, dietary supplementation with t-10, c-12 conjugated linoleic acid (CLA) decreased the weight gain induced by high fat diet compared with WD (p<0.01) and was accompanied by hyperinsulinemia (p<0.05) in the ApoE-/- and hypoadiponectinemia (p<0.01) in both mice strains. Although t-10, c-12 CLA supplementation increased plasma lipids and was associated with profound liver steatosis there was a reduction in atherosclerotic lesions in both mouse models (p<0.05). Analysis of mRNA and protein levels in the liver suggested that the differences in liver and plasma lipids may reflect inappropriate lipogenic response to t-10,c-12 CLA. In the high fat and fructose-fed hamster, the modulating role of fish fatty acids was investigated. The addition of DHA increased weight gain and adiposity compared to EPA and c-9, t-11 CLA supplementation. However, glucose tolerance was improved after 6 weeks of DHA supplementation (p? 0.01). Using [35S]methionine radiolabelling, DHA supplementation decreased apolipoprotein B100 synthesis and secretion. Newly synthesized cellular and secreted TG, as measured by [3H]glycerol incorporation, were also decreased with DHA supplementation. Although the effects of EPA were similar to those with DHA, the magnitude was generally lower. These results suggest that supplementation with fish fatty acids can improve several of the risk factors of the metabolic syndrome. Taken together, these observations indicate that some, but not all, bioactive fatty acids may be useful supplements for mediating cardiovascular risk factors.

Key aspects of the basic agronomy Camelina sativa were evaluated under controlled environment conditions and at multiple field locations in 2011 and 2012. Camelina is a highly adaptable crop. It germinates well even under low water availability and has a great potential for yield compensation. The line CDI007 was the most promising genotype with the highest yield potential, the lowest glucosinolate content, and the highest tolerance to downy mildew. The optimum N rate for seed yield varied by year and location: 100 kg N/ha at Truro and Canning in 2011, 120-150 kg N/ha at Canning, Truro and New Glasgow, 160-200 kg N/ha at Fredericton in 2012. N was positively correlated with protein content, but negatively correlated with oil content. Application of sulphur increased protein content at all of the sites and yield at some of the sites. In general, camelina response to S was maximized when N was sufficient.

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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.