Modulation of colon inflammation in interleukin-10 gene-deficient mice via dietary polyunsaturated fatty acid
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE12028 | GEO | 2008/07/10
SECONDARY ACCESSION(S): PRJNA113305
REPOSITORIES: GEO
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Project description:Dietary n-3 polyunsaturated fatty acids can reduce inflammation via a range of mechanisms. This study tested the effect of dietary eicosapentaenoic acid (EPA) on intestinal inflammation using interleukin-10 gene-deficient (Il10-/-) mice. Methods: At 35 days of age, 12 weaned Il10-/- and 12 C57 mice were randomly assigned to one of two modified AIN-76A diets, supplemented with 3.7% purified ethyl esters of either EPA (n-3) or oleic acid (OA, control). To identify genes relevant to colon inflammation, transcription profiling (microarrays and qRT-PCR) and bioinformatic analyses were used. Results: In this study, dietary EPA reversed the decrease in colon fatty acid β-oxidation gene expression observed in OA-fed Il10-/- compared to C57 mice. Il10-/- mice fed the OA diet showed decreased expression of antioxidant enzyme genes, as well as those involved in detoxification of xenobiotics, compared to C57 mice on the same diet. In contrast, dietary EPA increased the expression of these genes in Il10-/- mice. Conclusions: These data indicate that dietary EPA induced endogenous lipid oxidation which might have a potential anti-inflammatory effect on colon tissue. This is supported by the activation of the Ppara gene that regulates the expression of pro-inflammatory and immunomodulatory genes and proteins. Experiment Overall Design: The diet abbreviations EPA, OA, AA and CO used in the sample records Experiment Overall Design: refer to the following : Experiment Overall Design: CO : AIN-76A (control) Experiment Overall Design: OA : AIN-76A (fat-free) + 1% corn oil + 3.7% oleic acid Experiment Overall Design: EPA : AIN-76A (fat-free) + 1% corn oil + 3.7% eicosapentaenoic acid Experiment Overall Design: AA : AIN-76A (fat-free) + 1% corn oil + 3.7% arachidonic acid Experiment Overall Design: Corn oil was supplemented with purified linoleic and alpha-linolenic acid to meet the nutritional requirements of mice for these essential fatty acids. Diets fed for 6 weeks.
2008-10-21 | E-GEOD-12028 | biostudies-arrayexpress
Project description:Metabolically healthy skeletal muscle is characterized by the ability to switch easily between glucose and fat oxidation, whereas loss of this ability seems to be related to insulin resistance. The aim of this study was to investigate whether different fatty acids (FAs) and the LXR ligand T0901317 affected metabolic switching in human skeletal muscle cells (myotubes). Pretreatment of myotubes with eicosapentaenoic acid (EPA) increased suppressibility, the ability of glucose to suppress FA oxidation, and metabolic flexibility, the ability to increase FA oxidation when changing from “fed” to “fasted” state. Adaptability, the capacity to increase FA oxidation with increasing FA availability, was increased after pretreatment with EPA, linoleic acid (LA) and palmitic acid (PA). T0901317 counteracted the effect of EPA on suppressibility and adaptability, but did not affect these parameters alone. EPA itself accumulated less, however, EPA, LA, OA and T0901317 increased the number of lipid droplets (LDs) in myotubes, whereas LD size and mitochondria amount were independent of pretreatment. Microarray analysis showed that EPA regulated more genes than the other FAs. Some pathways involved in carbohydrate metabolism were induced only by EPA. The present study suggests a possible favorable effect of EPA on skeletal muscle metabolic switching and glucose utilization. Keywords: Analysis of target gene regulation by using microarrays. Primary human myotubes, derived from 3 healthy, female donors, were preincubated with different fatty acids (oleic acid [OA], palmitic acid [PA], eicosapentaenoic acid [EPA] or linoleic acid [LA], each at 100 µM) or bovine serum albumin [BSA] (40 µM) for 24 h.
2010-06-23 | E-GEOD-18589 | biostudies-arrayexpress
Project description:Metabolically healthy skeletal muscle is characterized by the ability to switch easily between glucose and fat oxidation, whereas loss of this ability seems to be related to insulin resistance. The aim of this study was to investigate whether different fatty acids (FAs) and the LXR ligand T0901317 affected metabolic switching in human skeletal muscle cells (myotubes). Pretreatment of myotubes with eicosapentaenoic acid (EPA) increased suppressibility, the ability of glucose to suppress FA oxidation, and metabolic flexibility, the ability to increase FA oxidation when changing from “fed” to “fasted” state. Adaptability, the capacity to increase FA oxidation with increasing FA availability, was increased after pretreatment with EPA, linoleic acid (LA) and palmitic acid (PA). T0901317 counteracted the effect of EPA on suppressibility and adaptability, but did not affect these parameters alone. EPA itself accumulated less, however, EPA, LA, OA and T0901317 increased the number of lipid droplets (LDs) in myotubes, whereas LD size and mitochondria amount were independent of pretreatment. Microarray analysis showed that EPA regulated more genes than the other FAs. Some pathways involved in carbohydrate metabolism were induced only by EPA. The present study suggests a possible favorable effect of EPA on skeletal muscle metabolic switching and glucose utilization. Keywords: Analysis of target gene regulation by using microarrays.
2010-06-23 | GSE18589 | GEO
Project description:Epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are involved in the initiation and maintenance of intestinal inflammation. LMD is a technique that allows the extraction of specific cell types, such as colonic epithelial cells, to analyse gene expression. LMD of colon epithelial cells followed by microarray analysis could be of more value than microarray analysis of intact colon for determining which pathways are active in the colon mucosa in the early and late stages of inflammation due to increased sensitivity to changes in specific cell populations. An experiment was performed using microarray analysis of intact colon samples and microdissected colon epithelial cell samples from Il10-/- and C57BL/6J mice at 6 and 12 weeks of age to study the molecular changes that occur in early and late inflammation stages in colon epithelium of a mouse model of colitis. Results showed that intact colon and colon epithelial cell gene expression profiles were similar in terms of pathways between Il10-/- and C57BL/6J mice at 12 weeks of age and between Il10-/- mice at 12 and 6 weeks of age. More immune-related pathways were identified at 6 weeks of age in epithelial cells than intact colon. This suggests that LMD and targeting of specific cell types may be of particular use when studying the early stages of inflammation before the intestinal morphology is detectably altered, by increasing analysis sensitivity to mucosal gene expression changes. 2x2 factorial with two tissue types analysed. Two strains of mouse (Il10 knockout mouse and the background strain C57BL/6J) were sampled at 2 timepoints (6 and 12 weeks of age) and intact proximal colon and colon epithelium harvested from each mouse (6 mice per group except for group colon epithelium C57 mouse 12 weeks where only 5 samples reached quality control standards).
2013-03-01 | E-GEOD-39859 | biostudies-arrayexpress
Project description:Background: The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport proteins and metabolic enzymes, often collectively called âintestinal barrier proteinsâ. An important receptor that mediates the effects of dietary lipids on gene expression is the peroxisome proliferator-activated receptor alpha (PPARα), which is abundantly expressed in enterocytes. In this study we examined the effects of acute nutritional activation of PPARα on expression of genes encoding intestinal barrier proteins. To this end we used triacylglycerols composed of identical fatty acids in combination with gene expression profiling in wild-type and PPARα-null mice. Treatment with the synthetic PPARα agonist WY14643 served as reference. Results: We identified 74 barrier genes that were PPARα-dependently regulated 6 hours after activation with WY14643. For eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and oleic acid (OA) these numbers were 46, 41, and 19, respectively. The overlap between EPA-, DHA-, and WY14643-regulated genes was considerable, whereas OA treatment showed limited overlap. Functional implications inferred form our data suggested that nutrient-activated PPARα regulated transporters and phase I/II metabolic enzymes were involved in a) fatty acid oxidation, b) cholesterol, glucose, and amino acid transport and metabolism, c) intestinal motility, and d) oxidative stress defense. Conclusion: We identified intestinal barrier genes that were PPARα-dependently regulated after acute activation by fatty acids.This knowledge provides a better understanding of the impact dietary fat has on the barrier function of the gut, identifies PPARα as an important factor controlling this key function, and underscores the importance of PPARα for nutrient-mediated gene regulation in intestine. Experiment Overall Design: Pure bred wild-type (129S1/SvImJ) and PPARα-null (129S4/SvJae) mice were treated for 6 hours with the synthetic triacylglycerols triolein [oleic acid (OA, C18:1)], trieicosapentaenoin [eicosapentaenoic acid (EPA, C20:5)] or tridocosahexaenoin [ocosahexaenoic acid (DHA, C22:6)], or the potent PPARα agonist WY14,643. Two weeks before the start of the experiment, mice were put on a modified AIN76A diet, in which corn oil was replaced by olive oil. At the day of the experiment mice were fasted for four hours. At 9 AM mice were dosed by oral gavage with 400 µl of a 0.1% WY14643 suspension in 0.5% carboxymethyl cellulose, or 400 µl of the synthetic triacylglycerols. Six hours after the gavage the mice were anaesthetized, small intestines were removed, flushed with ice-cold PBS and remaining fat and pancreatic tissue was carefully removed. Total RNA was then isolated. RNA of 4-5 biological replicates was hybridized to Affymetrix 430-2.0 plus arrays. Five microgram total RNA was labelled according to the ENZO-protocol, fragmented and hybridized according to Affymetrix's protocols.
2008-06-18 | E-GEOD-9533 | biostudies-arrayexpress
Project description:Background: The selective absorption of nutrients and other food constituents in the small intestine is mediated by a group of transport proteins and metabolic enzymes, often collectively called ‘intestinal barrier proteins’. An important receptor that mediates the effects of dietary lipids on gene expression is the peroxisome proliferator-activated receptor alpha (PPARα), which is abundantly expressed in enterocytes. In this study we examined the effects of acute nutritional activation of PPARα on expression of genes encoding intestinal barrier proteins. To this end we used triacylglycerols composed of identical fatty acids in combination with gene expression profiling in wild-type and PPARα-null mice. Treatment with the synthetic PPARα agonist WY14643 served as reference. Results: We identified 74 barrier genes that were PPARα-dependently regulated 6 hours after activation with WY14643. For eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and oleic acid (OA) these numbers were 46, 41, and 19, respectively. The overlap between EPA-, DHA-, and WY14643-regulated genes was considerable, whereas OA treatment showed limited overlap. Functional implications inferred form our data suggested that nutrient-activated PPARα regulated transporters and phase I/II metabolic enzymes were involved in a) fatty acid oxidation, b) cholesterol, glucose, and amino acid transport and metabolism, c) intestinal motility, and d) oxidative stress defense. Conclusion: We identified intestinal barrier genes that were PPARα-dependently regulated after acute activation by fatty acids.This knowledge provides a better understanding of the impact dietary fat has on the barrier function of the gut, identifies PPARα as an important factor controlling this key function, and underscores the importance of PPARα for nutrient-mediated gene regulation in intestine. Keywords: metabolic state analysis
2008-05-22 | GSE9533 | GEO
Project description:It was found that after OA treatment, compared with the CK group, the abundance of lactic acid bacteria in the intestinal flora of mice in the OA group increased, and the increase in the abundance of lactic acid bacteria made the gene Il10 upregulated, Il10 had a significant effect on tumor volume reduction and prolongation of mouse survival, and played a role through cytokine receptor interaction pathway.
2024-03-13 | GSE231570 | GEO
Project description:Dietary polyunsaturated fatty acids (PUFA) act as potent natural hypolipidemics and are linked to many health benefits in humans and in animal models. Mice fed long-term a high fat diet, in which medium-chain alpha linoleic acid (ALA) was partially replaced by long-chain docosahexaenoic (DHA) and eicosapentaenoic (EPA) fatty acids, showed reduced accumulation of body fat and prevention of insulin resistance, besides increased mitochondrial beta-oxidation in white adipose tissue and decreased plasma lipids. ALA, EPA and DHA all belong to PUFA of n-3 series. The intestine is a gatekeeper organ for ingested lipids. To examine the potential contribution of the intestine in the beneficial effects of EPA and DHA, this study assessed gene expression changes using whole genome microarray analysis on small intestinal scrapings. The main biological process affected was lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial beta-oxidation, and omega-oxidation of fatty acids were all increased. Quantitative real time PCR and intestinal fatty acid oxidation measurements ([14C(U)]-palmitate) confirmed significant gene expression differences in a dose-dependent manner. Furthermore, no major changes in the expression of lipid metabolism genes were observed in colonic scrapings. In conclusion, we show that marine n-3 fatty acids regulate small intestinal gene expression patterns. Since this organ contributes significantly to whole organism energy use, this adaptation of the small intestine may contribute to the complex and observed beneficial physiological effects of these natural compounds under conditions that will normally lead to development of obesity and diabetes. Experiment Overall Design: Male 4-month-old C57BL/6J mice were maintained for 4 weeks on semisynthetic high-fat (20% wt/wt) diets differing in the composition of n-3 PUFA. Two isocaloric diets were used (n=12): control sHFf diet which contained flax-seed oil (rich in ALA) as the only lipid source, or the sHFf-F2 diet, which had the same composition except that 44 % of the lipids were replaced by a n-3 PUFA concentrate (EPA&DHA) containing 6 % EPA and 51 % DHA (EPAX 1050TG; EPAX AS, Lysaker, Norway). Quality control of RNA samples showed that four samples did not pass quality thresholds, and these samples were excluded from array analysis (two control small intestine samples and one EPA&DHA small intestine sample). The remaining RNA samples were pooled per tissue per diet group. Thus; the flax-seed (control) array was hybridized with RNA pooled from of 10 mice, the PUFA array was hybridized with RNA pooled from 11 mice.
2009-04-16 | E-GEOD-11936 | biostudies-arrayexpress
Project description:Lcn2 is involved in host defense against pathogens, but the function in intestinal mucosal immunity and inflammation remains largely unknown. Genetic ablation of Lcn2 results in early-onset colitis and spontaneous emergence of right-sided colonic tumors in the setting of IL-10 deficiency (Lcn2-/-;IL10-/- mice). To address whether inflammation or other mechanisms drives the site-specific tumor locations gene expression analyses in proximal versus distal colons of Lcn2-/- IL10-/- mice were performed. Differential expression between distal colon versus cecum and proximal colon samples were analyses using Affymetrix MoGene 2.0 ST arrays on formalin-fixed, paraffin-embedded tissue sections of Lcn2-/-; IL10-/-mice.
2016-03-30 | E-MTAB-4583 | biostudies-arrayexpress
Project description:A total of 30 male IL10-/- (B6.129P2-Il10<tm1Cgn>/J) and 30 male C57 control (C57BL/6J) mice were obtained from The Jackson Laboratory (Bar Harbor, Maine, USA). All mice were between 28 and 35 days of age at the start of the study. For convenience and consistency in reporting, their age was defined as 35 days or 5 weeks of age. The mice were housed individually in standard shoebox size cages containing untreated wood shavings and maintained in an air-conditioned animal room with a 12-h light-dark cycle. Animals had free access to water and were fed an AIN-76A standard powder diet prepared in-house. This study was approved by the AgResearch Ruakura Animal Ethics Committee in Hamilton, New Zealand according to the Animal Protection Act (1960) and Animal Protection Regulations (1987) and amendments. Four days after arrival, all mice were inoculated orally with a mixture of Enterococcus faecalis strains and bacteria commonly found in the intestinal lumen to obtain a more consistent and reproducible intestinal inflammation. Mice were randomly assigned to five sampling groups (7, 8.5, 10, 12 and 14 weeks of age). Experiment Overall Design: For the comparison of gene expression levels, colonic RNA of IL10-/- and C57 at 7 and 12 weeks of age were compared because of a low HIS variability in the colon within those time points. A reference design with 15 arrays was used, where each individual RNA sample was hybridized with a reference sample onto the array, in a total of 3 or 4 biological replicates per treatment. Reference RNA was prepared by pooling equal amounts of purified total RNA extracted from small intestine, colon, kidney, liver and fetuses from normal, healthy Swiss mice.
2009-09-18 | E-GEOD-17990 | biostudies-arrayexpress