Intestinal tract cancer is one of the more common cancers in the United States. While in some individuals a genetic component causes the cancer, the rate of cancer in the remainder of the population is believed to be affected by diet. Since cancer usually develops slowly, the amount of oxidative damage to DNA can be used as a cancer biomarker. This dissertation examines effective ways of analyzing FLARE assay data, which quantifies oxidative damage. The statistical methods will be implemented on data from a FLARE assay experiment, which examines cells from the duodenum and the colon to see if there is a difference in the risk of cancer due to corn or fish oil diets. Treatments of the oxidizing agent dextran sodium sulfate (DSS), DSS with a recovery period, as well as a control will also be used. Previous methods presented in the literature examined the FLARE data by summarizing the DNA damage of each cell with a single number, such as the relative tail moment (RTM). Variable skewness is proposed as an alternative measure, and shown to be as effective as the RTM in detecting diet and treatment differences in the standard analysis. The RTM and skewness data is then analyzed using a hierarchical model, with both the skewness and RTM showing diet/treatment differences. Simulated data for this model is also considered, and shows that a Bayes Factor (BF) for higher dimensional models does not follow guidelines presented by Kass and Raftery (1995). It is hypothesized that more information is obtained by describing the DNA damage functions, instead of summarizing them with a single number. From each function, seven points are picked. First, they are modeled independently, and only diet effects are found. However, when the correlation between points at the cell and rat level is modeled, much stronger diet and treatment differences are shown both in the colon and the duodenum than for any of the previous methods. These results are also easier to interpret and represent graphically, showing that the latter is an effective method of analyzing the FLARE data.

Major therapeutics against Alzheimer's disease (AD) are targeted towards reducing beta-amyloid in the brain and improving cognitive performance. Transgenic mouse models of AD have become critical in the development of such therapeutics to protect against or treat AD. This dissertation examined the potential protective effects of both active A-beta immunotherapy and dietary omega-3 fatty acid administration to AD transgenic mice. First, immunization with A-beta 1-42 from 2-16 1/2 months of age provided protection against cognitive impairment in APP/PS1 transgenic mice well into older age. At both adult (4 1/2-6 month) and aged (15-16 1/2 month) test points, an extensive 6-week behavioral battery was administered that measured multiple sensorimotor and cognitive domains. A-beta immunotherapy either partially or completely protected APP/PS1 mice from impairment in reference learning/memory, working memory and/or recognition/identification at these test points. However, behavioral protection at the later test point occurred without any reduction in A-beta deposition within the brain. Therefore, the cognitive benefits of A-beta immunotherapy most likely involved neutralization or removal of A-beta oligomers from the brain. In addition to immunotherapy, this dissertation also examined the behavioral and neurochemical effects of a high omega-3 (n-3) or high omega-6 fatty acid (n-6) diet to NT and AD transgenic (Tg+) mice from 2 through 9 months of age. The same 6-week behavioral test battery, as described above, was administered between 7 1/2-9 months of age. In NT mice, dietary n-3 or n-6 fatty acids did not result in any beneficial effects on cognitive performance. In Tg+ mice, a high n-3 diet improved some, but not most, cognitive skills in comparison to standard-fed Tg+ mice; whereas a diet high in n-6 fatty acids did not lead to widespread deficits in learning or memory. In fact, there was no difference in overall performance on any behavioral task between Tg+ mice given a high n-3 or high n-6 diet. Administration of dietary fatty acids did not result in any significant changes in soluble or insoluble A-beta levels within the brains of Tg+ mice and plasma cytokine levels in Tg+ mice were largely unaffected. Notably, neither the high n-3 nor high n-6 diet increased cortical levels of n-3 or n-6 fatty acids, respectively, within Tg+ mice. However, NT mice on a high n-3 or high n-6 diet did show significant elevations in cortical n-3 or n-6 fatty acid levels, respectively, suggesting that Tg+ mice have a deficit in incorporation of dietary fatty acids in the brain. Collectively, these results show that life-long administration of active A-beta immunotherapy provides clear cognitive protection well into older age, whereas long-term dietary omega-3 fatty acid administration does not provide extensive cognitive benefit. Both studies underscore the value of using AD transgenic mice in determining the efficacy of prophylactics against AD.

n-3 polyunsaturated fatty acids (n-3 PUFA) have been postulated to improve the insulin resistance associated with type 2 diabetes since the 1960s when observational studies in the Alaskan Inuit noted a reduced prevalence of type 2 diabetes when this population consumed a traditional diet. These findings were supported by animal studies but results of human intervention studies have been variable with most showing no change in glucose metabolism. More recent studies in growing farm animals suggested that muscle membrane phospholipids required to be enriched to a minimum of 14% n-3 PUFA in order for a change in insulin sensitivity to occur. This study sought to establish the effect of long-term (9 month) high-dose (3g/day) supplement of the n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on insulin sensitivity of glucose and protein metabolism. Thirty-three subjects with impaired glucose regulation underwent hyperinsulinaemic-euglycaemic-euaminoacidaemic clamps pre- and postintervention of n-3 PUFA or a control (maize) oil. A second cohort who all received n-3 PUFA supplementation underwent pre- and post-intervention muscle biopsies. Secondary outcomes included an assessment of inflammatory status and determining whether erythrocyte membrane phospholipid could act as a surrogate for muscle membrane phospholipid. In the clamp cohort, there were no changes in glucose metabolism postintervention; however, there was an increase in insulin-stimulated protein metabolism following the fish oil intervention. In the biopsy cohort, no subject achieved 14% PUFA enrichment in muscle membrane phospholipids; however, all subjects who received n-3 PUFA supplementation did achieve a minimum of 14% enrichment of n-3 PUFA in erythrocyte membrane phospholipid. In agreement with the majority of the literature, n-3 PUFA did not affect glucose metabolism. Insulin-stimulated protein metabolism was improved supporting the findings of another recent human study. These changes in protein metabolism may reduce the sarcopenia associated with aging, potentially delaying the progression of frailty.

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Barley protein based microcapsules (1-5µm) incorporating fish oil/β-carotene were successfully prepared. Well suspended solid microcapsules, rather than emulsions, were able to form after high pressure emulsifying process. These wet-status microcapsules could be turned into dry powder by a spray drying process. The microcapsules demonstrated spherical shape and high loading capacity. Oxidative stability tests under accelerated conditions and in food formulations suggest barley proteins are effective microencapsulation materials to protect fish oil against oxidation. Microcapsule degradation and bioactive compound release behaviors were studied in the simulated gastro-intestinal tract. The data revealed that nano-encapsulations (20-30nm) were formed as a result of enzymatic degradation of microcapsule bulk matrix in the simulated gastric tract. These nano-encapsulations delivered β-carotene to a simulated human intestinal tract intact, where they were degraded by pancreatic enzymes and steadily released the β-carotene. These uniquely structured microcapsules may provide a new strategy to develop target delivery systems for nutraceuticals / Food Science and Technology

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / Ácidos graxos são moléculas bioativas endógenas e exógenas, que podem ser potentes mediadores e/ou reguladores de muitos processos celulares, no entanto, os seus efeitos no reparo de lesões cutâneas não estão bem esclarecidos. O objetivo deste trabalho foi investigar os efeitos da suplementação com diferentes óleos comestíveis na cicatrização de lesões cutâneas. Para isso, ratos Wistar machos (6-8 semanas/ 150200g) foram separados em quatro grupos: Um grupo controle (n=7) e três grupos experimentais (n=21). Trinta dias antes de realizarmos a lesão no dorso de cada animal, demos início a suplementação diária pelo método de gavagem com 1,5ml/kg de óleo de girassol, linhaça ou peixe e esta se manteve até o dia da eutanásia (d14). Em d0 uma lesão excional (1cm) foi realizada na parte dorsal de cada animal. A contração da lesão e re-epitelização foram medidas em d0, d7 e d14. Ao sacrificarmos os animais a lesão foi coletada juntamente com pele normal adjacente. O fechamento da lesão foi significativamente maior no grupo de controle (área lesada 58&#61617;2%) em d7, quando comparado com os outros grupos (grupo girassol 68&#61617;2%, linhaça 772% e peixe 732%) com p<0,05, para todos. Em d14 observamos menor área lesada no grupo controle (área lesada 211%) em relação aos grupos suplementados com óleo de linhaça e peixe (área lesada dos grupos linhaça 271% e peixe 271%), com p<0,05 para ambos os grupos. Não observamos diferença no fechamento da lesão quando comparamos os grupos controle (área lesada 211%) e girassol (área lesada 251%). Em relação ao infiltrado inflamatório observamos uma quantidade moderada nos grupos controle, linhaça e peixe, enquanto que no grupo girassol foram encontradas poucas células inflamatórias. Grande número de miofibroblastos foi observado nos grupos controle e girassol na região superficial do tecido de granulação. Entretanto, nos grupos linhaça e peixe observamos poucos miofibroblastos e muitos vasos sanguíneos dilatados. Os grupos controle e girassol apresentaram vasos sanguíneos ocluídos e concentrados na região profunda do tecido de granulação. Os grupos controle e girassol apresentaram densidade moderada de fibras colágenas na região profunda do tecido de granulação. Esse resultado foi confirmado através da dosagem de hidroxiprolina. Os níveis de hidroxiprolina estavam menores nos grupos controle e girassol quando comparados com os grupos linhaça e peixe. A suplementação com diferentes tipos de óleos comestíveis retarda o processo de contração da lesão e afeta o infiltrado inflamatório e a deposição de fibras colágenas / Fatty acids are bioactive molecules, but their effects on cutaneous wound healing are not well elucidated. Our aim was to investigate effects of supplementation with different edible oils on cutaneous wound healing. Thirty days before wounding, male Wistar rats started to receive daily (g.o.), 1.5 ml/kg of linseed, fish (n-3) or sunflower (n-6) oils and continued supplementation until euthanasia. In d0 an excional wound (1cm) was performed in the back of each animal. Wound contraction and re-epithelialization were measured d0, d7 and d14, when animals were sacrificed the wound and adjacent normal skin were collected. Wound closure was significantly higher in the control group (wound area 582%) in d7 when compared to other groups (wound area of sunflower group 682%; linseed 772% and fish 732%; with p<0.05, respectivelly) Fourteen days after wounding, wound closure was significantly higher in control group (wound area of control group 211%) when compared to linseed and fish groups (wound area of linseed 271% and fish 271%), with p<0.05 for both. There was no difference in wound closure between control (wound area of control group 211%) and sunflower groups (wound area of 251%). Inflammatory cells were abundant in control, linseed and fish groups, while in the sunflower group were scarce. Large amount of myofibroblasts was observed in control and sunflower groups in the superficial region of granulation tissue (p<0.01, respectivelly). Linseed and fish groups presented high density of dilated blood vessels. Control and sunflower groups presented blood vessels occluded and concentrated in the deep region of granulation tissue. Control and sunflower groups showed moderate density of collagen fibers in deep region of granulation tissue; however, in linseed and fish groups showed high density of collagen fibers. These observations were confirmed through determination of collagen concentration using hydroxyproline assay. The hidroxyproline levels were smaller in the control and sunflower groups than in linseed and fish. The supplementation with different types of edible oils delayed wound closure and affected inflammatory infiltrate and collagen deposition

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Fish oil sparing and replacement is a major focus in the fields of aquaculture and aquaculture nutrition. Most of the commercial fish oil production is consumed by the aquafeed industry due to its highly digestible energy and elevated content of long-chain polyunsaturated fatty acids (LC-PUFAs; ARA – 20:4n-6, EPA – 20:5n-3, and DHA – 22:6n-3), being a valuable ingredient. Given the finite supply and the growing demand for fish oil its price has increased quite drastically, leading to the search for alternative lipid sources. Generally, vegetable- and terrestrial animal-origin alternatives lack LC-PUFAs, which are physiologically important nutrients for all fish, and considered essential fatty acids for carnivorous species. When fish oil is spared or replaced by alternative lipids fish survival, growth performance, and fish health are commonly impaired if adequate levels of essential fatty acids are not provided within feeds. Additionally, fish oil sparing typically distorts fillet fatty acid profile and associated nutritional value compared to a fish oil-based diet reflecting the composition of the alternative lipid used. It is clear that to address the fish oil bottleneck in aquafeed manufacturing, researchers must understand the essential fatty acid requirements of the key commercial fish species. Fatty acid essentiality in fish has been investigated, and there is preliminary evidence that not all LC-PUFAs may be equally required, with DHA being more important, and EPA being more expendable. Whereas ARA has not been investigated in the same extent as n-3 LC-PUFAs. Additionally, certain fatty acids groupings such as saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) may influence LC-PUFAs bioavailability, and in some cases maintain or enhance LC-PUFAs deposition. The current dissertation sought to provide new knowledge regarding LC-PUFA requirements of marine carnivorous fish (White Seabass Atractoscion nobilis, California Yellowtail Seriola lalandi and Florida Pompano Trachinotus carolinus) in the context of C18 PUFA-rich (i.e. polyunsaturated fatty acid with chain length of 18 carbon atoms) and SFA- and MUFA-rich alternative lipids. Determine if all LC-PUFAs (ARA, EPA, DHA) are equally important in meeting fatty acids requirements and also determine the effects of dietary SFA, MUFA, and C18 PUFA content in fish oil sparing and tissue deposition of LC-PUFAs. The overall findings highlighted that DHA and ARA appear to be the primary drivers of fatty acid essentiality, whereas EPA is likely required in minor amounts. It was also demonstrated that DHA/EPA ratio had little-to-no effect on fish performance. Additionally, LC-PUFA requirements seem to be more flexible than previously assumed being influenced by dietary fatty acid profile. LC-PUFAs in marine finfish are more bioavailable in the context of SFA-/MUFA-rich alternative lipids, thus, reducing the requirements for these nutrients and allowing the fish’s physiological demand to be met with dietary levels below the minimum levels recommended. Finally, these findings suggest that although marine fish accept a variety of alternative lipids, those rich in SFAs and/or MUFAs seem advantageous in terms of limiting the effects of fish oil sparing on tissue fatty acid profiles.

Seafood represents the most important source of long-chain polyunsaturated fatty acids (LC-PUFAs) in the human diet. However, consuming fish can present risks from persistent organic pollutants (POPs) that bioaccumulate in edible tissues following dietary exposure. In farmed fish, POPs accumulate as a result of feeding diets based on fish oil (FO). Fish oil substitution can reduce POP accumulation, but also results in loss of beneficial LC-PUFAs. Fish oil-based finishing diets at the end of production can restore LC-PUFAs, but this strategy also increases POPs. The present study assessed the use of saturated fatty acid (SFA)-rich lipids to replace fish oil in grow-out feeds in conjunction with a fish oil-rich finishing diet to determine if this strategy could produce hybrid striped bass with equal production performance, equivalent LC-PUFA levels, and reduced POP concentrations. Triplicate tanks of hybrid striped bass were raised on diets containing fish oil (100% FO), fish oil spiked with additional POPs (100% FO Spike), or blends (50/50 or 25/75) of FO and coconut (CO) or palm (PO) oils (50% CO, 50% PO, 75% CO, 75% PO) with and without an eight week finishing period with the 100% FO diet prior to harvest. Production performance, fillet LC-PUFA, and POP content were assessed. Production performance was not adversely affected by any of the feeding regimens. However, fatty acid profile was altered, with fillets of fish consuming less fish oil having lower LC-PUFA and POP levels. Finishing yielded a modest increase in fillet LC-PUFAs and POPs, but POPs accumulated more readily than LC-PUFAs during finishing. However, harvest fillet POP and LC-PUFA levels in the experimental groups were lower relative to levels in the 100% FO group. Replacing fish oil in aquafeeds can produce fish with reduced LC-PUFAs, and also reduced POPs. Feeding fish oil results in more rapid accumulation of POPs than LC-PUFA. Overall, the 75% fish oil replacement feeds yielded fish with the highest ratio of LC-PUFAs to POPs. Despite lower LC-PUFA content, fillets of fish fed the 75% fish oil replacement feeds could be incorporated into a weekly meal plan with other dietary sources of LC-PUFAs to meet dietary recommendations for these essential nutrients.

Seafood is the number one source of essential fatty acids, particularly, long-chain polyunsaturated fatty acids (LC-PUFA) in the human diet. As global population growth eventually surpasses what the world's wild commercial stocks can provide, reliance on the aquaculture industry to expand production will continue to increase in order to meet the demands of consumers worldwide. Currently, fluctuations in supply and cost coupled with environmental sustainability and contaminant concerns have motivated the aquaculture industry to research alternative lipid sources and feeding strategies in order to reduce the reliance on marine-derived resources. For most cultured species, replacing fish oil with terrestrial plant-based lipid sources is a minor dietary modification that has little consequence on production performance. However, fish raised on these plant-based lipid alternatives contain considerably higher medium chain polyunsaturated fatty acids (MC-PUFA) and n-6 fatty acids and less beneficial LC-PUFA and n-3 fatty acids within the fillets, thus negatively impacting the nutritional value of cultured seafood to the consumer. In order to alleviate this problem, producers can employ finishing strategies to restore fillet LC-PUFA content prior to harvest. As a complement to this approach, provision of dietary saturated fatty acids (SFA) and/or monounsaturated fatty acids (MUFA) in lieu of MC-PUFA appears to maximize the retention of LC-PUFA deposition during the grow-out period and may increase deposition during finishing. Accordingly, my objectives were to 1) assess whether the SFA, MUFA, and MC-PUFA content of the alternative lipid affected LC-PUFA levels in Nile Tilapia fed reduced fish oil feeds; and 2) using the optimal alternative lipid identified in the first objective, assess increasing fish oil replacement rates in conjunction with finishing to maximize product nutritional value and minimize fish oil usage in Nile Tilapia culture. To address the first objective, I assessed production performance and tissue composition of Nile Tilapia fed diets containing fish oil or blends of fish oil and various soybean-derived alternative lipids. Quadruplicate tanks of juvenile Nile Tilapia were fed diets containing fish oil (FISH, high in LC-PUFA) or a 50:50 blend of fish oil and standard (STD-SO, high in MC-PUFA), saturated fatty acid-enriched (SFA-SO, high in SFA), low α-linolenic (LO-ALA-SO, high in MC-PUFA), or hydrogenated (HYD-SO, high in MUFA) soybean oil for 16 weeks. Partial replacement of fish oil with soybean oils did not significantly affect production performance with the exception of the HYD-SO diet which yielded significantly reduced growth efficiency in comparison with some of the experimental diets, though not the FISH control. Despite distinctly different dietary fatty acid profiles, fillet fatty acid composition was similar among fish fed the FISH, SFA-SO, and HYD-SO diets. However, feeding the STD-SO and LO-ALA-SO diets resulted in significant enrichment of less desirable MC-PUFA and n-6 fatty acids within the fillet. Fillet LC-PUFA levels were equivalent among all groups despite the 50% reduction in dietary LC-PUFA intake among fish fed the soybean oil-based feeds. Based on these results, incorporation of STD-SO, SFA-SO, or LO-ALA-SO could be used as partial replacements for fish oil in Nile Tilapia feeds without impairing production performance, though SFA-rich soybean oils appeared to be the best alternative for maintaining a more "fish oil"-associated fillet fatty acid profile. Accordingly, the SFA-enriched soybean oil was selected for further study in the second objective trial that evaluated the effects of graded levels of fish oil replacement without or without implementation of finishing periods on production performance and fillet fatty acid composition. Nile Tilapia were fed feeds containing 100% fish oil (100-FO), the previously assessed SFA-enriched soybean oil (100-SFA-SO), or blends of fish oil and SFA-enriched soybean oil (50-SFA-SO, 75-SFA-SO). Triplicate groups of fish were fed the aforementioned diets exclusively throughout the feeding trial (100-SFA-SO unfinished, 75-SFA-SO unfinished, 50-SFA-SO unfinished) or in conjunction with 4 or 8 weeks of finishing with the 100-FO feed (100-SFA-SO + 4 wks, 100-SFA-SO + 8 wks, 75-SFA-SO + 4 wks, 75-SFA-SO + 8 wks, 50-SFA-SO + 4 wks, 50-SFA-SO + 8 wks) for a total of 20 weeks. Production performance was unaffected by dietary inclusion of SFA-enriched soybean oil when fed exclusively or in combination with fish oil, though growth performance was lower than observed in the previous trial and likely confounded by behavioral interactions and frequent spawning. After 12 weeks of consuming the SFA-enriched soybean oil grow-out diets, fillet levels of n-3 LC-PUFA were not statistically different from 100-FO control levels despite different levels of dietary inclusion. However, the high dietary levels of SFA in the experimental feeds did not translate into increased fillet SFA content, suggesting selective retention of LC-PUFA at the expense of fillet SFA. Finishing for 4 or 8 weeks increased fillet n-3 LC-PUFA content in all groups, though it appears that the 50- and 75-SFA-SO diets were more successful in maintaining acceptable health promoting n-3:n-6 ratios. Based on these results, SFA-enriched soybean oil-based feeds can be used as a cost-saving measure during grow-out, and the effects of these feeds on fillet fatty acid profile can be reversed to a considerable extent in as little as 4 weeks by implementing a finishing period prior to harvest. This approach is a promising strategy for minimizing fish oil usage while maximizing product value of cultured Nile Tilapia.