Endothelial activation is considered to be an early and critical event in the pathology of atherogenesis which can be modified by environmental factors such as diet, pollutants, and lifestyle habits. Dietary andamp;ugrave;-6 and andamp;ugrave;-3 fatty acids have been reported to either amplify or diminish inflammatory responses related to atherosclerosis development. However, the interactions of andamp;ugrave;-6 and andamp;ugrave;-3 fatty acids with inflammatory cytokines or organic pollutants on endothelial cell activation are not well understood. The studies presented in this dissertation tested the hypothesis that andamp;ugrave;-6 and andamp;ugrave;-3 fatty acids alone, or in varying ratios can differently modulate pro-atherogenic mediators and inflammatory responses that are initiated by tumor necrosis factor- andamp;aacute; (TNF-andamp;aacute;) or polychlorinated biphenyls (PCBs) in endothelial cells. Exposure to TNF-andamp;aacute; induced oxidative stress, p38 MAPK, NF-andamp;ecirc;B, COX-2 and PGE2, which was amplified by pre-enrichment with linoleic acid but blocked or reduced by andamp;aacute;-linolenic acid. Furthermore, TNF-andamp;aacute;-induced caveolin-1 up-regulation and the co-localization of TNF receptor-1 with caveolin-1 was markedly increased in the presence of linoleic acid and diminished by andamp;aacute;-linolenic acid. Silencing of the caveolin-1 gene completely blocked TNF-andamp;aacute;-induced production of COX-2 and PGE2 and significantly reduced the amplified response of linoleic acid plus TNF-andamp;aacute;. These data suggest that omega-6 and omega-3 fatty acids can differentially modulate TNF-andamp;aacute;-induced inflammatory stimuli and that caveolae and its fatty acid composition play a regulatory role in these observed metabolic events. Besides cytokines, lipophilic environmental contaminants such as PCBs can also trigger inflammatory events in endothelial cells. Our data suggest that increasing the relative amount of andamp;aacute;-linolenic acid to linoleic acid can markedly decrease oxidative stress and NF-andamp;ecirc;B-responsive genes. The inhibitor study revealed that the modulation effect of andamp;ugrave;-6 and andamp;ugrave;-3 fatty acids on PCB toxicity was mainly through the oxidative stress sensitive transcription factor, NF-andamp;ecirc;B. In conclusion, our studies demonstrate that different dietary fats can selectively modulate vascular cytotoxicity caused by TNF-andamp;aacute; as well as by persistent organic pollutants such as PCBs. We also demonstrated the important relevance of substituting dietary andamp;ugrave;-3 fatty acids such as andamp;aacute;-linolenic acid for andamp;ugrave;-6 fatty acid such as linoleic acid in reducing cardiovascular diseases.

Although it is well-established that the fatty acid profile of breast milk will reflect the dietary fatty acids, the response time with which this occurs is not known. We hypothesized that fatty acids from a given meal would be transferred acutely from chylomicrons into breast milk. To test this hypothesis, the following experiment was performed. Fourteen lactating women drank 700 Calorie breakfast formulas containing six different test fats: 40 grams of cocoa butter, coconut, safflower or canola oil, 20 grams of menhaden oil or 7 grams of herring oil. Each fat contained a specific fatty acid whose appearance was tracked in the milk. After consuming the breakfast formula, subjects collected mid-feeding milk samples at 0, 6, 10, 14 and 24 hours, and one morning sample on days two through seven. Fatty acids specifically tracked in milk samples were: C12:0 (coconut oil), C18:0 (cocoa butter), C18:2n-6 (safflower oil), C18:3n-3 (canola oil), C22:ln-ll (herring oil), and C20:5n-3 and C22:6n-3 (menhaden oil). There was a significant increase in each of these fatty acids in human milk (p<0.001). Elevation of these fatty acids was first observed at 6 hours. Maximum increases of these fatty acids occurred 10 h after safflower oil (177% of baseline), 14 hours after cocoa butter (154%), coconut oil (216%), canola oil (206%) and menhaden oil (C20:5n-3 [1157%]), and 24 hours after the herring oil (2621%) and menhaden oil (C22:6n-3 [506%]). Compared to baseline, these fatty acids were significantly elevated (p<0.05) from 10 to 24 hours. However, after menhaden oil, C20:5n-3 was significantly elevated for 3 days and C22:6n-3 for 2 days. These data support the hypothesis that there is an acute transfer of dietary fatty acids from chylomicrons into human milk. / Graduation date: 1996

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The objectives of this study were to investigate the different characteristics of the newly introduced breed, Waguli (Wagyu x Tuli) when comparing it with the Brahman breed. Twenty-four animals were used. Six steers of each breed were fed 94% concentrate diet (94C) and the other six were fed 86% concentrate diet (86C). Eight steers, two from each group, each were harvested at 128 days, 142 days, and 156 days on feed. Feedlot performance data indicated that Waguli steers were highly efficient (P < 0.05) and gained more than Brahman steers on a daily basis (P < 0.05). Carcass characteristic data showed that Waguli steers have larger ribeye area with more 12th rib fat thickness, marbling score and higher quality grade (P < 0.05). It is well known that Wagyu is a highly marbled and tender Japanese breed. It was found that the reason for the Waguli tenderness and low shear force values to be the low level of calpastatin activity (P < 0.05), the inhibitor of the postmortem proteolytic enzyme-calpain. While the toughness of the Brahman meat was due to the high level of calpastatin activity. The calpain activity did not differ between the two breeds. Shear force values agreed with the calpain and calpastatin activities data, in which the Waguli steaks showed less shear force values at day 7 and 10 postmortem than the Brahman steaks (P < 0.05). However, at day 14 postmortem there was no difference in shear force values between the two breeds (P < 0.05). Fatty acid data analysis indicated that Waguli steers had a profile with less saturated fatty acids (SFA) and more unsaturated fatty acids (UFA) content than those in Brahman steers fat. Looking at the ratio of unsaturated fatty acids (UFA) to saturated fatty acids (SFA), it is observed that Waguli steers had a greater ratio than Brahman steers. In conclusion, Waguli steers produce tender meat with good marbling ability, which likely to satisfy the consumers demand. In addition, they have a desirable average daily gain and feed efficiency with high polyunsaturated fatty acids comparatively with Brahman steers.

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