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Classification of diet modified gene signatures at the colon cancer initiation and progression stages

ABSTRACT: We used DNA microarrays to identify discriminative gene signatures for the purpose of classifying n-3 PUFA-fed, carcinogen injected Sprague Dawley rats at the initiation and progression stages. Animals were assigned to three dietary treatments differeing only in the type of fat (corn oi/n-6 PUFA, fish oil/n-3 PUFA, or olive oli/n-9 monounsaturated fatty acid). The effects of diet on colonic mucosal gene expression signatures during tumor initiation with the progression of colon cancer. Each dietary lipid source exhibited its own unique transcriptional profile, as assessed by linear discriminant analysis. Applying this novel approach we identified the single genes and the two- to three-gene combinations that best distinguished the dietary treatment groups. For the chemoprotective fish oil diet, mediators of stem cell homeostasis, e.g., ephrin B1 and bone morphogenic protein 4, were the top-permorming gene classifiers. keywords: diet analysis 29 samples were analyzed. 10 samples had repeat arrays. No control or reference samples were included.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Jennifer Goldsby

PROVIDER: E-GEOD-25912 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Salmon liver proteomics - Preliminary Validation of a High Docosahexaenoic Acid (DHA) and -Linolenic Acid (ALA) Dietary Oil Blend: Tissue Fatty Acid Composition and Liver Proteome Response in Atlantic Salmon (Salmo salar) Smolts

Project description:Novel DHA-enriched oils with high α-linolenic acid (ALA) content will be available in the near future as an alternative for dietary fish oil replacement in aquafeeds. As preliminary validation, we 1) assessed the ability of a diet containing a formulated oil blend (tuna oil + flaxseed oil, TOFX) with high DHA and ALA content to achieve fish oil-like omega-3 long-chain (≥C20) polyunsaturated fatty acids (n-3 LC-PUFA) tissue composition in Atlantic salmon smolts, and 2) applied liver proteomics as exploratory approach to understand the consequent nutritional changes. Comparisons were made on fish fed a fish oil-based diet (FO) and a commercial-like oil blend diet (fish oil + poultry oil, FOPO) over 89 days. Growth and feed efficiency ratio were lower on the TOFX diet. Fish tissue concentration of n-3 LC-PUFA and the n-3:n-6 ratio were significantly higher for TOFX than for FOPO, but not higher than for FO, while tissue retention efficiency of n-3 LC-PUFA was promoted by TOFX relative to FO. Proteomics analysis revealed an unexpected oxidative stress response as the main adaptive physiological mechanism in TOFX fish. While specific dietary fatty acid concentrations and balances and antioxidant supplementation may need further attention, the use of an oil with a high content of DHA and ALA can enhance tissue deposition of n-3 LC-PUFA in relation to a commercially used blend oil.

2018-03-01 | PXD004114 | Pride

Nutritional evaluation of an EPA-DHA oil from transgenic Camelina sativa in feeds for post-smolt Atlantic salmon (Salmo salar L.)

Project description:Vegetable oils (VO) are possible substitutes for fish oil in aquafeeds but are limited by their lack of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). However, oilseed crops can be modified to produce n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, representing a potential option to fill the gap between supply and demand of these important nutrients. Camelina sativa was metabolically engineered to produce a seed oil with around 15 % total n-3 LC-PUFA to potentially substitute for fish oil in salmon feeds. Post-smolt Atlantic salmon (Salmo salar) were fed for 11-weeks with one of three experimental diets containing either fish oil (FO), wild-type Camelina oil (WCO) or transgenic Camelina oil (DCO) as added lipid source to evaluate fish performance, nutrient digestibility, tissue n-3 LC-PUFA, and metabolic impact determined by liver transcriptome analysis. The DCO diet did not affect any of the performance or health parameters studied and enhanced apparent digestibility of EPA and DHA compared to the WCO diet. The level of total n-3 LC-PUFA was higher in all the tissues of DCO-fed fish than in WCO-fed fish with levels in liver similar to those in fish fed FO. Endogenous LC-PUFA biosynthetic activity was observed in fish fed both the Camelina oil diets as indicated by the liver transcriptome and levels of intermediate metabolites such as docosapentaenoic acid, with data suggesting that the dietary combination of EPA and DHA inhibited desaturation and elongation activities. Expression of genes involved in phospholipid and triacylglycerol metabolism followed a similar pattern in fish fed DCO and WCO despite the difference in n-3 LC-PUFA contents.

2016-12-05 | E-MTAB-4621 | biostudies-arrayexpress

Differential effects of krill oil and fish oil on the hepatic transcriptome in mice

Project description:Dietary supplementation with ω-3 polyunsaturated fatty acids (ω-3 PUFAs), specifically the fatty acids docosahexaenoic acid (DHA; 22:6 ω-3) and eicosapentaenoic acid (EPA; 20:5 ω-3), is known to have beneficial health effects including improvements in glucose and lipid homeostasis and modulation of inflammation. To evaluate the efficacy of two different sources of ω-3 PUFAs, we performed gene expression profiling in the liver of mice fed diets supplemented with either fish oil or krill oil. We found that ω-3 PUFA supplements derived from a phospholipid krill fraction (krill oil) downregulated the activity of pathways involved in hepatic glucose production as well as lipid and cholesterol synthesis. The data also suggested that krill oil-supplementation increases the activity of the mitochondrial respiratory chain. Surprisingly, an equimolar dose of EPA and DHA derived from fish oil modulated fewer pathways than a krill oil-supplemented diet and did not modulate key metabolic pathways regulated by krill oil, including glucose metabolism, lipid metabolism and the mitochondrial respiratory chain. Moreover, fish oil upregulated the cholesterol synthesis pathway, which was the opposite effect of krill supplementation. Neither diet elicited changes in plasma levels of lipids, glucose or insulin, probably because the mice used in this study were young and were fed a low fat diet. Further studies of krill oil supplementation using animal models of metabolic disorders and/or diets with a higher level of fat may be required to observe these effects. Twenty-one microarrays: three diets (CO, FO, KO) x seven mice per diet x one microarray per mouse

2011-07-21 | E-GEOD-29572 | biostudies-arrayexpress

Fish oil/pectin temporally alters gene expression profiles in exfoliated rat colonocytes throughout oncogenesis

Project description:We have demonstrated that fish oil/pectin (FO/P) diets protect against colon cancer compared to corn oil/cellulose (CO/C) by upregulating apoptosis and suppressing proliferation. To elucidate the mechanisms whereby FO/P diets induce apoptosis and suppress proliferation during the tumorigenic process, we analyzed the temporal gene expression profiles from exfoliated rat colonocytes. KEYWORDS: Fish oil/pectin, pectin, exfoliated colonocytes, gene expression, apoptosis, colon cancer, chemoprevention Rats consumed diets containing FO/P or CO/C and were injected with azoxymethane (AOM, 2x, 15 mg/kg BW, s.c.). Feces collected at the initiation, aberrant crypt foci (ACF), and tumor stages of colon cancer (24 h (n=20), 7 wk (n=37), and 28 wk (n=28) after AOM injection, respectively) was used for poly A(+) RNA extraction. Gene expression signatures were determined using Codelink arrays.

2012-02-20 | E-GEOD-27266 | biostudies-arrayexpress

An oil containing EPA and DHA from transgenic Camelina sativa to replace marine fish oil in feeds for Atlantic salmon (Salmo salar L.)

Project description:New de novo sources of omega 3 (n-3) long chain polyunsaturated fatty acids (LC-PUFA) are required as alternatives to fish oil in aquafeeds in order to maintain adequate levels of the beneficial fatty acids, eicosapentaenoic and docosahexaenoic (EPA and DHA, respectively). The present study investigated the use of an EPA+DHA oil derived from a transgenic Camelina sativa in feeds for Atlantic salmon (Salmo salar) containing low levels of fishmeal (35 %) and fish oil (10 %), reflecting current commercial formulations, to determine the impacts on intestinal transcriptome, tissue fatty acid profile and health of farmed salmon. Post-smolt Atlantic salmon were fed for 12-weeks with one of three experimental diets containing either a blend of fish oil/rapeseed oil (FO), wild-type camelina oil (WCO) or transgenic camelina oil (DCO) as added lipid source. The DCO diet did not affect any of the fish performance or health parameters studied. Analyses of the mid and hindgut transcriptomes showed only mild effects on metabolism. Flesh of fish fed the DCO diet accumulated almost double the amount of n-3 LC-PUFA than fish fed the FO or WCO diets, indicating that these oils from transgenic oilseeds offer the opportunity to increase the n-3 LC-PUFA in farmed fish to levels comparable to those found twelve years ago.

2017-05-31 | E-MTAB-5529 | biostudies-arrayexpress

Classification of diet modified gene signatures at the colon cancer initiation and progression stages

Project description:We used DNA microarrays to identify discriminative gene signatures for the purpose of classifying n-3 PUFA-fed, carcinogen injected Sprague Dawley rats at the initiation and progression stages. Animals were assigned to three dietary treatments differeing only in the type of fat (corn oi/n-6 PUFA, fish oil/n-3 PUFA, or olive oli/n-9 monounsaturated fatty acid). The effects of diet on colonic mucosal gene expression signatures during tumor initiation with the progression of colon cancer. Each dietary lipid source exhibited its own unique transcriptional profile, as assessed by linear discriminant analysis. Applying this novel approach we identified the single genes and the two- to three-gene combinations that best distinguished the dietary treatment groups. For the chemoprotective fish oil diet, mediators of stem cell homeostasis, e.g., ephrin B1 and bone morphogenic protein 4, were the top-permorming gene classifiers. keywords: diet analysis

2010-12-09 | GSE25912 | GEO

Expression data from liver of young and old rats fed on different dietary fat sources, namely virgin olive, sunflower or fish oils

Project description:Since the liver is the central organ of metabolism, changes in diet have a great impact on this organ and overall on health with aging. It is well known that dietary fat source strongly influences many parameters of the hepatic mitochondria. These changes includes modification of lipid composition of mitochondrial membrane, affecting the mtETC functions, oxidative stress and mtDNA alterations. We used microarrays to detail the changes in gene expression provides by feeding lifelong on different dietary fat sources, and identified distinct classes of up and down-regulated genes during aging under different dietary conditions. Rats were fed lifelong on a normolipidic diet (4% w/w) with virgin olive, sunflower or fish oil as dietary fat source. At 6 and 24 months, animals were killed and liver were removed for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain changes in gene expression due to both aging and dietary conditions. There were 6 experimental groups (virgin olive oil at 6 months, sunflower oil at 6 months, fish oil at 6 months, virgin olive oil at 24 months, sunflower oil at 24 months and fish oil at 24 months. 3 animals were studied of each experimental group, so a total of 18 samples were analyzed.

2014-03-26 | E-GEOD-56166 | biostudies-arrayexpress

AQUAMAX cod

Project description:For aquaculture of carnivorous marine species to continue to expand, dietary fish oil must be replaced with more sustainable vegetable oil alternatives. Most vegetable oils are rich in n-6 polyunsaturated fatty acids (PUFA), specifically 18:2n-6, and their inclusion in feeds reduces the n-3/n-6 PUFA ratio of the fish flesh potentially compromising its nutritional quality. Few vegetable oils are rich in n-3 PUFA but one of these, Camelina oil (CO) is unique in that, in addition to high 18:3n-3 and a high n-3/n-6 PUFA ratio, it also contains substantial levels of C20 and C22 monoenes, similar to fish oil. Cod (initial weight ~0.8 Kg) were fed for 10 weeks with diets in which fish oil was replaced with graded amounts (0 M-bM-^@M-^S 100%) of CO. Growth performance, feed efficiency and fish biometric indices (HSI and VSI) was not significantly affected by increasing dietary CO. Lipid levels of liver tended to increase and those of flesh, decrease, with increasing dietary CO although the data were largely not statistically significant. Reflecting the diet, tissue n-3 long-chain PUFA (LC-PUFA) levels significantly decreased whereas levels of 18:3n-3 and 18:2n-6 increased with increasing inclusion of dietary CO. Dietary replacement of FO by Camelina oil did not appear to induce major metabolic changes in cod intestinal tissue, but rather potentially affected rates of cellular proliferation and death as well as induce changes in the structural properties of the intestinal muscle, most likely leading to different rates of tissue regeneration and/or repair, as well as changes in contractile activity or mechanical characteristics. Our results do not allow us to conclude on the underlying biological reasons explaining these molecular effects but given the important role of the intestine in overall nutrient absorption, further attention should be given to this organ in the future when examining effects of fish oil replacement by vegetable oils.

2011-09-01 | E-TABM-1178 | biostudies-arrayexpress

An EPA and DHA rich oil as a replacement to fish oil in Atlantic salmon aquafeeds: Effects on liver and pyloric caeca transcriptome

Project description:Facing a bottleneck in the growth of aquaculture, and a gap in the supply and demand of the highly beneficial omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA), sustainable alternatives to the traditional feeds are much needed. Therefore, in this trial, an oil extracted from newly designed plant, Camelina sativa, was tested for its n-3 replacement capabilities, using three different groups of post-smolt Atlantic salmon (Salmo salar) which were fed for 12 weeks three experimental diets; a control diet containing a blend of fish oil (5 %) and rapeseed oil (15 %) (FO), a wild-type Camelina (20 %) (WCO) and the transgenic Camelina oil (20 %) (DCO), all of them having the same basal composition. By comparing them, an overall evaluation of fish performance, fatty acid profile, feeds digestibility and gene expression was done. In the context of the new transgenic diet, there were no negative effects on the growth, survival rate or health of the fish. The whole fish n-3 levels were highest in the DCO-fed fish with EPA+DHA levels almost double compared to FO-fed fish and more than double when compared to WCO-fed ones, clearly suggesting the efficiency of the Camelina oil in providing competitive levels of n-3 LC-PUFA compared to the commercial “gold standard”.

2019-11-30 | E-MTAB-6228 | biostudies-arrayexpress

Assessment of a land-locked Atlantic salmon (Salmo salar L.) population as a potential genetic resource with a focus on long-chain polyunsaturated fatty acid biosynthesis

Project description:The natural food for Atlantic salmon (Salmo salar) in freshwater has relatively lower levels of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA) than found in prey for post-smolt salmon in seawater. Land-locked salmon such as the GullspÃ¥ng population feed exclusively on freshwater type lipids during its entire life cycle, a successful adaptation derived from divergent evolution. Studying land-locked populations may provide insights into the molecular and genetic control mechanisms that determine and regulate n-3 LC-PUFA biosynthesis and retention in Atlantic salmon. A two factorial study was performed comparing land-locked and farmed salmon parr fed diets formulated with fish or rapeseed oil for 8 weeks. The land-locked parr had higher capacity to synthesise n-3 LC-PUFA as indicated by higher expression and activity of desaturase and elongase enzymes. The data suggested that the land-locked salmon had reduced sensitivity to dietary fatty acid composition and that dietary docosahexaenoic acid (DHA) did not appear to suppress expression of LC-PUFA biosynthetic genes or activity of the biosynthesis pathway, probably an evolutionary adaptation to a natural diet lower in DHA. Increased biosynthetic activity did not translate to enhanced n-3 LC-PUFA contents in the flesh and diet was the only factor affecting this parameter. Additionally, high lipogenic and glycolytic potentials were found in land-locked salmon, together with decreased lipolysis which in turn could indicate increased use of carbohydrates as an energy source and a sparing of lipid.

2016-02-11 | E-MTAB-4464 | biostudies-arrayexpress

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