Fish Oil Supplementation in Gastrointestinal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Stomach Cancer,Gastrointestinal Neoplasms,Gastrointestinal Cancer,Colorectal Cancer,Colorectal Neoplasms,Stomach Neoplasms
PROVIDER: 2209534 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Colorectal cancer is the second leading cause of cancer-related death within the United States. Animal models and observational studies have suggested that marine-derived n-3 polyunsaturated fatty acids [PUFA] such as eicosapentanoic acid [EPA] and docosahexanoic acid [DHA] may reduce the risk of colorectal cancer. In addition, it may be the relative proportion of n-3 to n-6 PUFAs that best determines the chemopreventive effects of fish oils. This ratio is important because the n-6 PUFA, arachidonic acid (ARA), is converted via the cyclo-oxygenase (COX) pathway to prostaglandin E2 (PGE2), an inflammatory eicosanoid overproduced in colorectal neoplasms while EPA is converted to the anti-inflammatory prostaglandin E3 (PGE3). While the ratio of n-6 to n-3 PUFAs can be altered through dietary changes, genetic factors may also influence this ratio. Recent genetic studies have demonstrated that much of the tissue levels of ARA is determined by differences in a gene called fatty acid desaturase 1 (FADS1). FADS1 is the rate-limiting enzyme in the conversion of linoleic acid, the most commonly consumed PUFA in the Western diet, to ARA, and one particular genetic variant caller rs174537 is associated with lower fatty acid desaturase activity and subsequently lower tissue levels of ARA.
The study hypothesis is that individuals with genetically determined lower activity of FADS1 will derive greater benefit from fish oil supplementation than individuals with higher FADS1 activity because of lower tissue levels of ARA and subsequently a more favorable n-6 to n-3 PUFA ratio. To test this hypothesis the investigators will recruit 150 participants with recently identified adenomatous polyps and conduct a 6-month double blind 3 X 2 factorial randomized controlled trial. The first factor will be FADS1 genotype (GG, GT, and TT) and the second factor will be fish oil supplementation (fish oil versus placebo). The primary outcome will be the change in rectal epithelial cell growth and cell death. Secondary outcomes will include rectal epithelial cell expression of genes important in PGE2 production, rectal cell production of PGE2 and PGE3, rectal mucosal tissue levels of fatty acids, and changes in biomarkers of inflammation (C-reactive protein), adipokines (leptin, adiponectin), and markers of insulin sensitivity.
The specific aims include: 1) to determine the efficacy of fish oil supplements on rectal epithelial cell proliferation indexes and markers of rectal crypt apoptosis, and 2) to determine the effect of genetically-determined fatty acid desaturase 1 activity on fish oil supplementation for colorectal cancer chemoprevention. The investigators long-term objectives are to determine genetic factors that might influence the efficacy of fish oil supplementation in order to conduct a more definitive adenoma recurrence trial using marine-derived n-3 PUFAs. The investigators anticipate that fish oil will have anti-neoplastic effect and individuals with low FADS1 activity will have a greater response compared to individuals with high FADS1 activity
| 2130139 | ecrin-mdr-crc
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
Project description:Animal and epidemiological studies suggest that lycopene and fish oil may modify the risk or delay progression of prostate cancer, however, the molecular mechanisms involved are poorly understood. We examined the effects of these micronutrients on prostate gene expression in a double-blind placebo-controlled randomized clinical trial (Molecular Effects of Nutritional Supplements, MENS). Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (intervention B; n = 29) or fish oil (intervention C; n = 27) supplementation or placebo (intervention A; n = 28). Gene expression in morphologically normal prostate tissue was studied at baseline and at 3 months via cDNA microarray analysis. Differential gene expression and pathway analyses were performed to identify genes and pathways modulated by dietary intake of fish or tomato or by lycopene or fish oil supplementation.
2011-06-01 | E-GEOD-27140 | biostudies-arrayexpress
Project description:Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 week treatment withfenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased byfenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism, and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for PPARα, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis, and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent towards modulating plasma free fatty acids, cholesterol and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention.
2011-10-08 | GSE32706 | GEO
Project description:Beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 FAs) are generally well-known from epidemiological studies, but the various mechanisms of action are not completely clarified. Regulation of gene expression is one known mechanism of action, but only very limited data of regulated pathways in humans after n-3 FA supplementation are available. Up to now, no studies compared gene expression changes after n-3 FA supplementation between normolipidemic and dyslipidemic subjects. Therefore, the aim of this study was to investigate the effects of n-3 FA administration on whole genome expression profiles in the blood of normo- and dyslipidemic subjects. We conducted an intervention study with normo- and dyslipidemic men aged between 29 and 51 years, which were subdivided into four groups with a balanced age distribution and randomized to either six fish oil capsules per day providing 1.5 g docosahexaenoic acid and 1.0 g eicosapentaenoic acid or corn oil capsules rich in linoleic acid per day for a period of 12 weeks. Venous blood samples were collected at baseline as well as after 4 hours, 1 week and 12 weeks of supplementation. For each investigation time point, the samples of each group were pooled together to minimize inter-individual variability. All subjects have successfully completed the study, but for the microarray experiments, nine subject samples were excluded. Therefore, the microarray experiments are based on the following group characteristics: normolipidemic fish oil group (FO-N): pool of nine RNAs from normolipidemic subjects supplemented with fish oil; normolipidemic corn oil group (CO-N): pool of six RNAs from normolipidemic subjects supplemented with corn oil; dyslipidemic corn oil group (CO-D): pool of eight RNAs from dyslipidemic subjects supplemented with corn oil; dyslipidemic fish oil group (FO-D): pool of nine RNAs from dyslipidemic subjects supplemented with fish oil.
2012-05-30 | GSE34898 | GEO
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
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.
2011-07-22 | GSE29572 | GEO
Project description:Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 week treatment withfenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased byfenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism, and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for PPARα, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis, and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent towards modulating plasma free fatty acids, cholesterol and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention. Expression profiling of liver from mice fed control diet, fish oil or fenofibrate for 2 weeks.
2011-10-07 | E-GEOD-32706 | biostudies-arrayexpress
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
Project description:Beneficial effects of long-chain omega-3 polyunsaturated fatty acids (n-3 FAs) are generally well-known from epidemiological studies, but the various mechanisms of action are not completely clarified. Regulation of gene expression is one known mechanism of action, but only very limited data of regulated pathways in humans after n-3 FA supplementation are available. Up to now, no studies compared gene expression changes after n-3 FA supplementation between normolipidemic and dyslipidemic subjects. Therefore, the aim of this study was to investigate the effects of n-3 FA administration on whole genome expression profiles in the blood of normo- and dyslipidemic subjects. We conducted an intervention study with normo- and dyslipidemic men aged between 29 and 51 years, which were subdivided into four groups with a balanced age distribution and randomized to either six fish oil capsules per day providing 1.5 g docosahexaenoic acid and 1.0 g eicosapentaenoic acid or corn oil capsules rich in linoleic acid per day for a period of 12 weeks. Venous blood samples were collected at baseline as well as after 4 hours, 1 week and 12 weeks of supplementation. For each investigation time point, the samples of each group were pooled together to minimize inter-individual variability. All subjects have successfully completed the study, but for the microarray experiments, nine subject samples were excluded. Therefore, the microarray experiments are based on the following group characteristics: normolipidemic fish oil group (FO-N): pool of nine RNAs from normolipidemic subjects supplemented with fish oil; normolipidemic corn oil group (CO-N): pool of six RNAs from normolipidemic subjects supplemented with corn oil; dyslipidemic corn oil group (CO-D): pool of eight RNAs from dyslipidemic subjects supplemented with corn oil; dyslipidemic fish oil group (FO-D): pool of nine RNAs from dyslipidemic subjects supplemented with fish oil. The twenty normolipidemic and the twenty dyslipidemic subjects were subdivided into two groups. Thus, a total of four groups with ten men per group passed through the study. To realize a comparable mean age between groups, the formation of groups was performed by stratified allocation according to subject's age. The four study groups were randomly assigned to different study products by an uninvolved collaborator. Subjects ingested either six FO or six corn oil (CO) capsules per day for a period of twelve weeks. The daily n-3 PUFA intake via FO capsules was 2.7 g (1.14 g DHA and 1.56 g EPA). The predominant FA of the CO capsules was the omega-6 (n-6) PUFA linoleic acid (LA, 18:2n-6). Thus, the daily LA intake via CO capsules was 3.05 g LA. The subjects were instructed to ingest the capsules together with food, three in the morning and three in the evening, and to maintain their usual exercise and dietary habits throughout the intervention time. As an exception, at the first intervention day, all six capsules were ingested at the same time in the morning after a standardised breakfast. During each visit, fasting blood samples were collected by venepuncture. Additionally, participants completed a questionnaire to obtain information about changes in medication, dietary (e.g., changes in weekly fish intake, preferred fish dishes or species, respectively) and lifestyle habits (e.g., physical activity), as well as the tolerability of the capsules. This record summarizes the results of 16 microarrays. The samples originate from whole blood of normo- and dyslipidemic subjects supplemented with either fish oil or corn oil for 4 h, 1 week and 12 weeks. Microarrays were hybridized in a loop design with one common reference using a dye-swap approach.
2012-05-29 | E-GEOD-34898 | biostudies-arrayexpress