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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

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE25912 | GEO | 2010/12/09

SECONDARY ACCESSION(S): PRJNA135859

REPOSITORIES: GEO

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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 29 samples were analyzed. 10 samples had repeat arrays. No control or reference samples were included.

2010-12-09 | E-GEOD-25912 | biostudies-arrayexpress

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

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

Assessment of Histone Tail Modifications and Transcriptional Profiling During Colon Cancer and Role of fish oil/pectin Diet Against Colon Carcinogen

Project description:In an effort to gain insight into the extensive dimension of post-translational modifications in histones (including H3K4me3 and H3K9ac) and elucidate the chemoprotective impact of dietary bioactive compounds on transcriptional control in a colon cancer preclinical model, we generated high-resolution genome-wide RNA (RNA-Seq) and “chromatin-state” (H3K4me3-seq and H3K9ac-seq) maps for intestinal (epithelial colonocytes) crypts in rats treated with a colon carcinogen and fed bioactive (i) fish oil (ii) butyrate (in the form of a fermentable fiber a rich source of SCFA), (iii) a combination of fish oil plus butyrate or (iv) control diets. Poor correlation was observed between differentially transcribed (DE) and enriched genes (DERs) at multiple epigenetic levels in fat x fiber dietary combinations and in the presence/absence of carcinogen. We also demonstrated that the combinatorial diet (fish oil + pectin) was synergistically chemoprotective, and uniquely affected epigenetic profiles in the intestinal epithelium, e.g., upregulating lipid catabolism and beta-oxidation associated genes.

2017-09-08 | GSE87525 | GEO

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

Evaluation of a high-EPA oil from transgenic Camelina sativa in feeds for Atlantic salmon (Salmo salar L.): Effects on tissue fatty acid composition, histology and gene expression

Project description:Currently, the only sustainable alternatives for dietary fish oil (FO) in aquafeeds are vegetable oils (VO) that are devoid of omega-3 (n-3) long-chain polyunsaturated fatty acids (LC-PUFA). Entirely new sources of n-3 LC-PUFA such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids through de novo production is a potential solution to fill the gap between supply and demand of these important nutrients. Camelina sativa,was metabolically engineered to produce a seed oil (ECO) with > 20 % EPA and its potential to substitute for FO in Atlantic salmon feeds was tested. Fish were fed one of three experimental diets containing FO, wild-type camelina oil (WCO) or ECO as the sole lipid sources for 7-weeks. Inclusion of ECO did not affect any of the performance parameters studied and enhanced apparent digestibility of individual n-6 and n-3 PUFA compared to dietary WCO. High levels of EPA were maintained in brain, liver and intestine (pyloric caeca), and levels of DPA and DHA were increased in liver and intestine of fish fed ECO compared to fish fed WCO likely due to increased LC-PUFA biosynthesis based on up-regulation of the genes. Fish fed WCO and ECO showed slight lipid accumulation within hepatocytes similar to that with WCO, although not significantly different to fish fed FO. The regulation of a small number of genes could be attributed to the specific effect of ECO (311 features) with metabolism being the most affected category. The EPA oil from transgenic Camelina (ECO) could be used as a substitute for FO, however it is a hybrid oil containing both FO (EPA) and VO (18:2n-6) fatty acid signatures that resulted in similarly mixed metabolic and physiological responses.

2016-03-01 | E-MTAB-3268 | biostudies-arrayexpress

Dietary long-chain omega 3 fatty acids modify sphingolipid metabolism to facilitate asthmatic airway hyperreactivity

Project description:We report the effects of dietary n-3 polyunsaturated fatty acids (PUFAs) on sphingolipid metabolism and airway reactivity in the lung. Mice were fed a n3-PUFA enriched fishoil diet or an isocaloric control coconut oil-enriched diet (CO) for 8 weeks. The n-3 PUFA diet affected pulmonary sphingolipid metabolism, and airway reactivity, independent of inflammation or allergic sensitization. These findings support a role for pulmonary sphingolipid homeostasis in asthma and could have implications for the use of n-3 PUFA dietary supplements in asthma.

2022-08-01 | GSE203418 | GEO

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

Omega-3 fatty acids partially revert the metabolic gene expression profile induced by long-term calorie restriction

Project description:Calorie restriction (CR) consistently extends longevity and delays age-related diseases across several animal models. We have previously shown that different dietary fat sources can modulate life span and mitochondrial ultrastructure, function and membrane fatty acid composition in mice maintained on a 40% CR. In particular, animals consuming lard as the main fat source (CR-Lard) lived longer than CR mice consuming diets with soybean oil (CR-Soy) or fish oil (CR-Fish) as the predominant lipid source. In the present work, a transcriptomic analysis in liver and skeletal muscle was performed in order to elucidate possible mechanisms underlying the changes in energy metabolism and longevity induced by dietary fat in CR mice. After 8 months of CR, transcription downstream of several mediators of inflammation was inhibited in liver. In contrast, proinflammatory signaling was increased in the CR-Fish versus other CR groups. Dietary fish oil induced a gene expression pattern consistent with increased transcriptional regulation by several cytokines (TNF, GM-CSF, TGF-b) and sex hormones when compared to the other CR groups. The CR-Fish also had lower expression of genes involved in fatty acid biosynthesis and increased expression of mitochondrial and peroxisomal fatty acid b-oxidation genes than the other CR diet groups. Our data suggest that a diet high in n-3 PUFA, partially reverts CR-related changes in gene expression of key processes, such as inflammation and steroid hormone signaling, and this may mitigate life span extension with CR in mice consuming diets high in fish oil.

2015-08-10 | GSE71773 | GEO

Ozone-Induced Vascular Contractility and Pulmonary Injury are Differentially Impacted by Diets Enriched with Coconut Oil, Fish Oil, and Olive Oil

Project description:Fish oil, olive oil, and coconut oil dietary supplementation have several cardioprotective benefits, but it is not established if they can protect against air pollution-induced adverse effects. We hypothesized that these dietary supplements would attenuate ozone-induced systemic and pulmonary effects. Male Wistar Kyoto rats were fed either a normal diet, or a diet enriched with fish, olive, or coconut oil starting at 4 weeks of age for 8 weeks. Animals were then exposed to air or ozone (0.8 ppm), 4h/day for 2 consecutive days. The fish oil diet completely abolished phenylephrine-induced vasoconstriction that was increased following ozone exposure in the animals fed all other diets. Only the fish oil diet increased baseline levels of bronchoalveolar lavage fluid (BALF) markers of lung injury and inflammation. Ozone-induced pulmonary injury/inflammation were comparable in rats on normal, coconut oil, and olive oil diets with altered expression of markers in animals fed the fish oil diet. Fish oil, regardless of exposure, led to enlarged, foamy macrophages in the BALF that coincided with decreased mRNA expression of cholesterol transporters, cholesterol receptors, and nuclear receptors in the lung. Serum miRNA profile was assessed using small RNA-sequencing in normal and fish oil groups and demonstrated marked depletion of a variety of miRNAs, several of which were of splenic origin. No ozone-specific changes were noted. Collectively, these data indicate that while fish oil offered protection from ozone-induced aortic vasoconstriction, it increased pulmonary injury/inflammation and impaired lipid transport mechanisms resulting in foamy macrophage accumulation, demonstrating the need to be cognizant of potential off-target pulmonary effects that might offset the overall benefit of this vasoprotective dietary supplement.

2018-01-11 | GSE102015 | GEO

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