Comparative transcriptome analysis of yeast expressing the fungal desaturases
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ABSTRACT:
ORGANISM(S): Schizosaccharomyces pombe Saccharomyces cerevisiae
PROVIDER: GSE20155 | GEO | 2010/12/27
SECONDARY ACCESSION(S): PRJNA125613
REPOSITORIES: GEO
Similar Datasets
Project description:To study how the presence of PUFAs influences central cellular processes, and in order to perform lipidome, transcriptome and molecular studies we decided to use yeast as a model organism. We therefore co-expressed Δ12-desaturase and Δ6- desaturase genes from Mucor rouxii in S. cerevisiae with the objective to obtain a yeast strain that contains PUFAs, especially linoleic acid (LA, C18:2Δ9,12) and γ-linolenic acid (GLA, C18:3Δ6,9,12), in its membranes. The resulting yeast strain was analyzed in details in order to quantify the fluxes through the fatty acid biosynthetic pathways and the genome-wide transcriptional response to production of LA and GLA. Three recombinant yeasts were constructed and grown in glucose-limited condition. Steady-state cultures were harvested for RNA extraction and hybridization on Affymetrix microarrays. Comparative transcriptome analysis between S. cerevisiae recombinants expressing M. rouxii D12-desaturase (D12) and co-expressing D12-desaturase and D6-desaturase genes (D126) and the reference strain (REF) was implemented.
2010-12-27 | E-GEOD-20155 | biostudies-arrayexpress
Project description:Bioactive compounds, including some fatty acids (FAs), can induce beneficial effects on body fat-content and metabolism. In this work, we have used C. elegans as a model to examine the effects of several FAs on body fat accumulation. Both omega-3 and omega-6 fatty acids induced a reduction of fat content in C. elegans, with linoleic, gamma-linolenic and dihomo-gamma-linolenic acids being the most effective ones. These three FAs are sequential metabolites in PUFA synthesis pathway and the effects seem to be primarily due to dihomo-gamma-linolenic acid, being independent of transformation into omega-3 or arachidonic acid. Gene expression analyses show that peroxisomal beta oxidation is the main mechanism involved in this fat-loss. All these results point out the importance of further analysis of the activity of these omega-6 FAs, due to their potential application in obesity and related diseases. In order to elucidate the mechanisms underlying the fat loss induced by the omega-6 FAs LNA, GLA and DGLA, we analyzed the whole-transcriptome expression profiling in response to LNA, GLA and DGLA treatments in wild-type worms using Affymetrix C. elegans expression arrays.
2017-08-19 | GSE102802 | GEO
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.
2016-03-15 | E-GEOD-72123 | biostudies-arrayexpress
Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status.
2016-03-15 | GSE72123 | GEO
Project description:Ferroptosis is a form of regulated cell death driven by lipid peroxidation of polyunsaturated fatty acids (PUFAs). Endogenous PUFAs are nonconjugated PUFAs and their peroxidation proceeds via the hydrogen-atom transfer (HAT) mechanism. We previously reported that lipids with conjugated double bonds undergo lipid peroxidation mostly via a different mechanism, peroxyl radical addition (PRA), and were much more readily oxidizable than nonconjugated ones. In this study, we aim to elucidate the effects of various unsaturated lipids in sensitizing ferroptosis. We found that while some peroxidation-reactive lipids, such as 7-dehydrocholesterol, vitamins D3 and A, and coenzyme Q10, suppress ferroptosis, both nonconjugated and conjugated PUFAs enhanced cell death induced by RSL3, a ferroptosis inducer. Importantly, we showed that conjugated linolenic acid (CLA 18:3) could act as a ferroptosis inducer by itself and conjugated linoleic acid (CLA 18:2) was more potent in sensitizing cells to RSL3-induced cell death than any nonconjugated PUFAs. We next sought to elucidate the mechanism underlying the different ferroptosis-inducing potency of conjugated and nonconjugated PUFAs. Lipidomics revealed that conjugated and nonconjugated PUFAs are incorporated into distinct cellular lipid species. Furthermore, the different peroxidation mechanisms predict the formation of higher levels of reactive electrophilic aldehydes from conjugated PUFAs than nonconjugated PUFAs, which was confirmed by aldehyde-trapping and mass spectrometry. RNA sequencing revealed that protein processing in the endoplasmic reticulum and proteasome are among the most significantly upregulated pathways in cells treated with CLA 18:3, suggesting increased ER stress and activation of unfolded protein response. Significantly, using click chemistry, we observed increased protein adduction by oxidized lipids in cells treated with an alkynylated CLA 18:2 probe. These results suggest that protein damage by lipid electrophiles is a key step in ferroptosis.
2023-04-17 | GSE224249 | GEO
Project description:Birth is the first metabolic challenge that cardiomyocytes need to overcome as they reshape their fuel preference from glucose to fatty acids (FA) to optimize energy production in postnatal life. This adaptation is partly triggered by drastic post-partum environmental changes, yet the molecular players responsible for orchestrating cardiomyocyte maturation remain unknown. Here, we discover that maternal metabolite γ-linolenic acid (GLA) support this transition. Specifically, colostrum GLA acts as an agonist for Retinoid X Receptors (RXR), a family of ligand-activated transcription factors expressed from embryonic life in cardiomyocytes. Mice lacking RXR in embryonic cardiomyocytes showed an aberrant chromatin landscape that prevented the induction of RXR-dependent FA metabolism genes (mtFAH signature). This results in a defective metabolic transition with blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, which ultimately leads to perinatal lethal cardiac dysfunction. In vitro GLA supplementation in cardiomyocytes induced the expression of mtFAH signature in a RXR-dependent manner. Altogether, our study uncovers GLA/RXR axis as the fundamental mechanism by which maternal physiology commands metabolic functioning in perinatal hearts. This SuperSeries is composed of the SubSeries listed below.
2023-02-15 | GSE188998 | GEO
Project description:As representatives of n-6 and n-3 fatty acids, many studies have analyzed the use of soybean oil and linseed oil rich in linoleic acid (18:2n-6, LA) and α-linolenic acid (18:3n-3, LNA) as better substitutes for fish oil. In aquatic animals, different dietary ratios of LA and LNA could have significant effects on growth, lipid metabolism, immune response, and reproduction. To assess the nutritive value of these two fatty acids for the Chinese mitten crab (Eriocheir sinensis), we performed transcriptome analysis and proteomic analysis using label-free quantification of the hepatopancreas of mitten crabs fed with LA or LNA diet. Our results provide new insights for further investigation into the replacement of fish oil from mitten crabs with vegetable oils and enable us to better understand the different roles and nutrition value of LA and LNA in mitten crabs.
2019-08-14 | PXD009864 | Pride
Project description:We report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in human post-mortem ALS spinal cord and a Drosophila model of the most common genetic cause of FTD/ALS, a repeat expansion in C9orf72. To investigate lipid alterations, we performed lipidomics on C9FTD/ALS iPSC-neurons and post-mortem FTLD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). To determine whether this PUFA deficit contributes to neurodegeneration, we fed C9FTD/ALS flies PUFAs, which yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of the C9orf72 flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor induced neuronal death in C9FTD/ALS patient iPSC-neurons. These data implicate neuronal fatty acid saturation in the pathogenesis of FTD/ALS and suggest that interventions to increase PUFA levels specifically within neurons will be beneficial.
2024-11-15 | GSE255099 | GEO
Project description:In the present study, we explored the hypothesis that the fatty liver phenotype and associated gene expression changes associated with the specific deletion of the POR gene in adult mouse liver could be abrogated by supplementation of the mouse diet with the very long chain highly unsaturated fatty acids, arachidonic acid (C20:4ω6), eicosapentaenoic acid (C20:5ω3) and docosahexaenoic acid (C22:6ω3). We expected the fatty liver phenotype would not be reduced by the polyunsaturated fatty acids linoleic (C18:2ω6) or linolenic acid (C18:3ω3), since these accumulated in the fatty livers of LivPORKO animals. This proved to be the case. However, we also made two surprising observations. First, control animals fed a diet enriched in PUFA had fatty livers and gene expression profiles similar to animals fed a lard diet, which was deficient in both PUFA and HUFA. Second, while a diet enriched in HUFA did result in reduced steatosis in livers of the LivPOKO animals, fat accumulation was still elevated relative to controls. Array analyses indicated most differences in gene expression were related to fatty acid metabolism and could explain differences in fat accumulation in LivPORKO livers with dietary treatment.
2010-10-09 | GSE20944 | GEO
Project description:Experimental studies confirmed n-6 type polyunsaturated fatty acid as pro-carcinogenic factor and n-3 fatty acid as cancer restraining agent; though their mode of action on tumor cells are still unclear. To review the contrasting effect of omega-3 and omega-6 fatty acids over carcinoma by studying genomic alteration in treated cancer cells, two members from each family of PUFAs, namely EPA and DHA from n-3 PUFA family and, AA and LA from n-6 PUFA family was selected to treat four breast cancer cell lines: MDA-MB231, MDA-MB435S, HCC2218 and MCF-7 for two time period- 6hr and 24hr.
2006-03-29 | E-GEOD-4497 | biostudies-arrayexpress