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Conjugated linoleic acid (CLA) reduces adipose mass in several species. Studies were conducted to determine: 1) the effect of dietary trans10,cis12-CLA on growth, tissue fatty acid profile, mRNA expression for stearoyl-CoA desaturase (SCD) in adipose and liver, and mRNA expression for fatty acid synthase (FAS) in adipose of mice, 2) the effect of a dietary combination of trans-vaccenic acid (TVA) and trans10,cis12-CLA on delta9- desaturation, and 3) the effect of cis9,trans11-CLA, trans10,cis12-CLA, and carnitine palmitoyltransferase-1 (CPT-1) inhibitors on expression of mRNA for CPT-1 and fatty acid profile in mouse hepatocytes (AML-12) and human hepatoma cells (HepG2). In the first study, male or female mice were fed diets containing 0, 0.15%, or 0.30% trans10,cis12-CLA for 6 wk. Epididymal adipose weights (males) and inguinal adipose weights (females) decreased by 81% and 52%, respectively, in response to 0.30% trans10,cis12-CLA. Dry carcass weights decreased from 4.75 g for the control to 3.62 g for mice fed 0.30% trans10,cis12-CLA and the decrease was due to a reduction in ether extract. Liver weights increased linearly from 0.55 g (control) to 0.65 g (0.30% trans10,cis12-CLA). Dietary trans10,cis12-CLA (0.30%) reduced FAS and SCD mRNA in adipose by 60 and 30 % respectively, compared with the control, suggesting reduced lipogenesis and desaturation might be primary factors responsible for reducing body fat. In the second study, adult male or female mice were fed diets containing 0.40% TVA in combination with 0, 0.15, or 0.30% trans10,cis12-CLA for 10 d. Both TVA and trans10,cis12-CLA were incorporated into plasma, liver, adipose, muscle, and bone lipids proportional to their concentrations in the diets. Desaturation ratios were not affected in adipose, liver, and bone. However, ratios of 16:0 to 16:1 and 18:0 to 18:1 increased from 0.81 to 0.86 and 0.15 to 0.19 respectively, in response to dietary trans10,cis12-CLA (0.30%), suggesting inhibition of delta9 desaturation in muscle. In the third study, AML-12 or HepG2 cells were incubated with control media or media containing 15 uM etomoxir (ETM), 30 uM ETM, 15 uM hemipalmitoylcarnitinium (HPC), 30 uM HPC, 100 uM cis9,trans11-CLA, or 100 uM trans10,cis12-CLA for 24 h. Half the cells were harvested for analysis of fatty acids, mRNA for CPT-1, and cholesterol after 24 h. The remaining cells were incubated for an additional 24 h in control medium. Incorporation (% of total fatty acids) of trans10,cis12-CLA was greater than cis9,trans11-CLA in AML-12 (34 vs 23.6) and HepG2 (28 vs 18) cells. Cells incubated with trans10,cis12-CLA had higher ratios of 16:0 to 16:1, 18:0 to 18:1, and 18:2n6 to 20:4n-6, suggesting inhibition of delta9, delta5 , and delta6 desaturation. Cis9,trans11-CLA also reduced ratio of 18:2n-6 to 20:4n-6 in both cell lines. Trans10,cis12-CLA increased mRNA for CPT-1 in both cell lines compared with the control, suggesting enhanced oxidation of fatty acids. In addition, trans10,cis12-CLA caused a 4-fold and 5-fold increase in free cholesterol content of AML-12 and HepG2 cells, respectively. Overall, results demonstrated that trans10,cis12-CLA modulated lipid metabolism in tissues in vivo and altered fatty acid metabolism, cholesterol synthesis, and CPT-1 mRNA in hepatic cell lines in vitro. / Ph. D.

Skim, butter-derived aqueous phase, anhydrous milk fat, and fish oil were used to formulate ultra high temperature (UHT) processed extended shelf-life omega-3 fatty acid fortified dairy-based beverages with fat contents mimicking whole milk (3.25%). Oxidation of the lipids in the formulated beverages was investigated during storage for 35 days at 4 °C using GC/MS analysis, conjugated diene analysis, and headspace solid phase micro-extraction GC/MS (SPME-GC/MS) analysis of headspace. Omega-3 fatty acid fortified dairy-based beverages were produced that mimicked the physical properties of 3.25% fat whole milk. Oxidation resulted in only small changes in omega-3 lipid content and sensory analysis by an untrained panel indicated that the overall aroma was no different than that of commercially available UHT processed milk. An omega-3 fatty acid fortified dairy-based beverage was produced that delivered 440mg of omega-3 fatty acid per 8oz serving. When consumed daily, the beverage could provide the equivalent amount of omega-3 fatty acids recommended by the American Heart Association, and the equivalent amount of omega-3 fatty acids found in two fatty fish meals over the period of one week. Antioxidants were added to the lipid phase, immediately prior to processing, of additionally produced formulations to determine if a reduction in omega-3 lipid oxidation was observed. No overall reduction in oxidation was observed, as indicated by GC/MS and SPME-GC/MS analysis. Sensory analysis indicated that oxidative aromas increased during storage for the antioxidant and omega-3 fatty acid fortified dairy-based beverage. Ascorbyl palmitate was determined to have a pro-oxidative effect on the formulated omega-3 fortified dairy-based beverages. Antioxidants present in the commercial grade fish oil used for fortification were effective in controlling oxidation in the formulated omega-3 fatty acid fortified dairy-based beverages. / Master of Science

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.

Indiana University-Purdue University Indianapolis (IUPUI) / This dissertation studies the effects of fatty acids on prostate cancer. Prostate cancer is one of the most common malignant diseases in males in the U.S. Because of the slow progression of this disease, early intervention methods, especially, dietary fatty acid interventions are considered very important to control the disease in early stages. This study describes how the depletion of the enzyme for endogenous fatty acid synthesis, fatty acid synthase, influences the expression of enzymes that metabolize dietary fatty acids and show how dietary fatty acids affect prostate cancer protein expression and function. Fatty acid synthase is an oncoprotein overexpressed in prostate cancer and its expression is suppressed with omega-3 fatty acid treatment. This study finds that the depletion of fatty acid synthase by siRNA knockdown induces suppression of cyclooxygenase-2 and fatty acid desaturase-1. Our results also show that fish oil (omega-3 fatty acid), but not oleic acid (omega-9 fatty acid), suppresses prostate cancer cell viability. Assessment of fatty acid synthesis activity indicates that oleic acid is a more potent inhibitor than fish oil of de novo fatty acid biosynthesis. In addition, the inhibition of its activity occurs over several days while its effects on cell viability occur within 24 hours. To better understand this relationship, label free LC-MS/MS based mass spectrometry was carried out to determine global proteomic and phosphoproteomic profiles of the prostate cell line PC3, with longitudinal treatment with fish oil or oleic acid. With short-term fish oil treatment, sequestosome-1was elevated. Prolonged treatment induced downregulation of microseminoprotein, a proinflammation factor, as well as proteins in the glycolysis pathway. In the phosphoproteomics study, we confidently identified 828 phosphopeptides from 361 phosphoproteins. Quantitative comparison between fish oil or oleic acid treated groups and the untreated group suggests that the fish oil induces changes in phosphorylation of proteins involved in the pathways associated with cell viability and metabolic processes, with fish oil inducing significant decreases in the levels of phospho-PDHA1Ser232 and phospho-PDHA1Ser300 and they were accompanied by an increase in PDH activity, suggesting a role for n-3 polyunsaturated fatty acids in controlling the balance between lipid and glucose oxidation.