Helminth-induced prostaglandin signalling and dietary shifts in PUFA metabolism promote colitis-associated cancer.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1271426 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33803873_1.fastq.gz | Fastqsanger.gz | |||
| SRR33803873_2.fastq.gz | Fastqsanger.gz | |||
| SRR33803874_1.fastq.gz | Fastqsanger.gz | |||
| SRR33803874_2.fastq.gz | Fastqsanger.gz | |||
| SRR33803875_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 16 |
Similar Datasets
Project description:Oxylipins derived from dietary polyunsaturated fatty acids (PUFAs) are key determinants of intestinal health, homeostasis and inflammatory disorders, such as colitis-associated colorectal cancer (CAC). Previous research has independently linked a high dietary omega (ω)-6:ω-3 PUFA ratio, or intestinal helminth infection, to an increased risk of CAC. However, whether these two factors interact to exacerbate disease risk and whether oxylipins contribute to this is unknown. In this study, we report that infection with the helminth Heligmosomoides polygyrus bakeri (Hpb) exacerbates tumour formation when combined with a high ω-6:ω-3 PUFA ratio diet. Dietary increases in tumour burden correlated with heightened levels of arachidonic acid (AA) and AA-derived lipoxygenase (LOX) oxylipins in the colon, including the 12/15-LOX product 12-hydroxyeicosatetraenoic acid, prior to disease onset. Although helminth infection further increased the production of 12/15-LOX oxylipins and increased expression of Alox15, responsible for producing these metabolites, inhibition of cyclooxygenase-dependent prostaglandin production with aspirin prevented helminth-exacerbation of disease. Helminth-infected mice exhibited increased phosphorylation of β-catenin in the colon, which was inhibited by EP2 and 4 antagonists. Moreover, administration of an EP agonist increased tumour burden in naive mice fed a high w-6:w-3 PUFA ratio diet, to the levels seen in helminth-exacerbation of disease. These data suggest that dietary changes in fatty acid composition coordinate with helminth-induced activation of EP signalling to exacerbate tumour development.
2025-06-03 | GSE298815 | GEO
Project description:Chromatin Landscape of Macrophages Following Helminth Enzyme Exposure Targeting Prostaglandin Synthesis
| PRJNA1081279 | ENA
Project description:The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of chronic intestinal helminth infection, we identify helminthic glutamate dehydrogenase (heGDH) as an essential factor for parasite chronicity by using antibody mediated neutralization or treatment with exogenous recombinant heGDH. Macrophages efficiently internalize heGDH and represent a major target of the enzyme in vivo. Combining RNA-seq, ChIP-seq, targeted lipidomics and inhibitor studies, we identify prostaglandin E2 (PGE2) as a major immune regulatory mechanism of heGDH. The induction of PGE2 and further immune regulatory factors (IL-12 family cytokines, IDO1) by heGDH depended on the p300-mediated acetylation of histones. While the enzyme’s catalytic activity was dispensable for key immune regulatory functions, an N-terminal handle-like structure distinct from mammalian GDHs may confer interaction of heGDH with its targets (CD64, GPNMB), identified via proteomics. Thus, helminths employ a ubiquitous metabolic enzyme to epigenetically target macrophages and establish chronicity.
2025-03-15 | GSE259349 | GEO
Project description:The prostaglandin D2 receptor CRTH2 suppresses epithelial responses during intestinal helminth infection
| PRJNA625445 | ENA
Project description:Gene expression profile of Macrophages Following Helminth Enzyme Exposure Targeting Prostaglandin Synthesis
| PRJNA1081278 | ENA
Project description:The molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of chronic intestinal helminth infection, we identify helminthic glutamate dehydrogenase (heGDH) as an essential factor for parasite chronicity by using antibody mediated neutralization or treatment with exogenous recombinant heGDH. Macrophages efficiently internalize heGDH and represent a major target of the enzyme in vivo. Combining RNA-seq, ChIP-seq, targeted lipidomics and inhibitor studies, we identify prostaglandin E2 (PGE2) as a major immune regulatory mechanism of heGDH. The induction of PGE2 and further immune regulatory factors (IL-12 family cytokines, IDO1) by heGDH depended on the p300-mediated acetylation of histones. While the enzyme’s catalytic activity was dispensable for key immune regulatory functions, an N-terminal handle-like structure distinct from mammalian GDHs may confer interaction of heGDH with its targets (CD64, GPNMB), identified via proteomics. Thus, helminths employ a ubiquitous metabolic enzyme to epigenetically target macrophages and establish chronicity.
2025-03-15 | GSE259350 | GEO
Project description:The objectives of this study were to examine the effect of (i) dietary supplementation with n-3 PUFA and (ii) post-insemination plane of nutrition on the global transcriptome of uterine endometrial tissue, with particular focus on key genes and pathways that may affect pregnancy outcome. A total of 60 estrous-synchronised continental crossbred heifers were offered a concentrate-based diet supplemented (n-3 PUFA; n=32) or not (Control; n=28) with an n-3 PUFA-enriched product for 30 days prior to insemination. Following insemination, animals were allocated, within treatment, to one of two post insemination diets, either remaining on their existing high plane of nutrition (Control + High (n = 14); n-3 PUFA + High (n = 15)), or fed a low plane of nutrition diet (Control + Low (n = 14); n-3 PUFA + Low (n = 17)). Uterine endometrial tissue was collected, RNA isolated and gene expression analysis conducted using RNAseq. Comparison of transcript abundance across groups, highlighted a significant effect of diet on the endometrial transcriptome. The mTOR signalling pathway as well as pathways involved in early pregnancy/fertility was significantly enriched as a consequence of diet.
2020-12-07 | GSE141937 | GEO
Project description:Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the main site of glucose uptake, effectiveness of T2D treatment depends in large on the improvement of insulin sensitivity and metabolic adaptability of the muscle. We have shown previously in mice fed an obesogenic high-fat diet that a combination treatment using n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinedione (TZD) anti-diabetic drugs preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether TZD rosiglitazone could elicit the additive beneficial effects on metabolic flexibility when combined with n-3 LC-PUFA. Adult male C57BL/6N mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various dietary treatments: (i) cHF+F, cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids; (ii) cHF+ROSI, cHF with 10 mg rosiglitazone/kg diet; and (iii) cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combination treatment. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the single treatments, with rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism, and n-3 LC PUFA supporting complete oxidation of fatty acids in mitochondria. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combination treatment using n-3 LC-PUFA and TZDs could improve the efficacy of the treatment of obese and diabetic patients.
2012-09-07 | GSE36716 | GEO
Project description:Impaired resistance to insulin, the key defect in type 2 diabetes (T2D), is associated with a low capacity to adapt fuel oxidation to fuel availability, i.e., metabolic inflexibility. The hampered metabolic adaptability triggers a further damage of insulin signaling. Since skeletal muscle is the main site of glucose uptake, effectiveness of T2D treatment depends in large on the improvement of insulin sensitivity and metabolic adaptability of the muscle. We have shown previously in mice fed an obesogenic high-fat diet that a combination treatment using n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and thiazolidinedione (TZD) anti-diabetic drugs preserved metabolic health and synergistically improved muscle insulin sensitivity. We investigated here whether TZD rosiglitazone could elicit the additive beneficial effects on metabolic flexibility when combined with n-3 LC-PUFA. Adult male C57BL/6J mice were fed an obesogenic corn oil-based high-fat diet (cHF) for 8 weeks, or randomly assigned to various dietary treatments: (i) cHF+F, cHF with n-3 LC-PUFA concentrate replacing 15% of dietary lipids; (ii) cHF+ROSI, cHF with 10 mg rosiglitazone/kg diet; and (iii) cHF+F+ROSI, or chow-fed. Indirect calorimetry demonstrated superior preservation of metabolic flexibility to carbohydrates in response to the combination treatment. Metabolomic and gene expression analyses in the muscle suggested distinct and complementary effects of the single treatments, with rosiglitazone augmenting insulin sensitivity by the modulation of branched-chain amino acid metabolism, and n-3 LC PUFA supporting complete oxidation of fatty acids in mitochondria. These beneficial metabolic effects were associated with the activation of the switch between glycolytic and oxidative muscle fibers, especially in the cHF+F+ROSI mice. Our results further support the idea that the combination treatment using n-3 LC-PUFA and TZDs could improve the efficacy of the treatment of obese and diabetic patients.
2012-09-07 | GSE36717 | GEO
Project description:Dietary consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against cardiometabolic disease through modulation of systemic and adipose inflammation. However, it is often difficult to detect the subtle effects of n-3 PUFA on inflammatory biomarkers in traditional intervention studies. We aimed to identify novel n-3 PUFA modulated gene expression using unbiased adipose transcriptomics during evoked endotoxemia in a clinical trial of n-3 PUFA supplementation. We analyzed adipose gene expression using RNA sequencing in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) trial of healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=8; 3600mg/day EPA/DHA) for 6weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (lipopolysaccharide 0.6ng/kg i.v.). As expected, supplementation with n-3 PUFA vs. placebo alone had only modest effects on adipose tissue gene expression. In contrast, the transcriptomic response to evoked endotoxemia was significantly modified by n-3 PUFA supplementation, with several genes demonstrating significant n-3 PUFA gene-nutrient interactions. These data highlight potential mechanisms whereby n-3 PUFA consumption may enhance the immune response to an inflammatory challenge.
2016-12-29 | GSE87426 | GEO