Plasma fatty acids depletion: a metabolic signature related to colon cancer
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ABSTRACT:
PROVIDER: PRJNA1113373 | ENA |
REPOSITORIES: ENA
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Project description:Understanding the complex interplay between tumor biology and host metabolism presents a formidable challenge with important clinical implications. At the local level, metabolic alterations of tumor cells and tumor microenvironment is a well-recognized process and constitute one of the major hallmarks of cancer cells. Consequently, research has largely isolated tumor biology from systemic metabolic dynamics, overlooking their potential interrelation. Nonetheless, cancer pathology is also very clearly associated with broad systemic metabolic disturbances, as exemplified by the frequent development of cachexia, which reaches up to 40% of colon cancer (CC) patients. Other metabolic alterations observed associated with cancer include insulin resistance, hypercalcemia, and amino acid metabolism, which underline the extensive systemic impact of cancer on the metabolic networks. In addition to these alterations, another interesting yet less studied phenomenon in cancer pathology is the observation that cancer patients present alterations of their typical fatty acid profiles in circulation. Evidence of this phenomenon is limited and scattered across the literature, although some studies have identified this alteration in patients with colorectal and liver cancer. Nonetheless, discerning whether these lipid profile shifts signify an intrinsic metabolic alteration or are secondary to factors such as malnutrition, adipose tissue dynamics, or clinical parameters like tumor staging and location has yet to be determined. It is evident that addressing this issue requires a more comprehensive analysis of the possible factors involved. Our study adopted an integrative methodology to study this process in CC, combining advanced body composition analysis, nutritional assessments, extensive clinical and transcriptomic data of the tumor, and precise profiling of esterified fatty acids in plasma. This multifaceted strategy has enabled us to confirm that the alteration of FA levels is a frequent phenomenon in patients with CC.
2025-05-28 | GSE267846 | GEO
Project description:In the present study, we investigated the consequences of n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic lipid metabolism in mice fed during three months with a diet presenting a high n-6/n-3 PUFA ratio to induce n-3 PUFA depletion. Microarray analyses were performed to identify the molecular targets involved in the development of hepatic steatosis associated with n-3 PUFA depletion.
2011-08-26 | GSE26986 | GEO
Project description:Solid evidence indicates that intake of marine n-3 fatty acids lower serum triglycerides, and that replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) reduces plasma total cholesterol and LDL-cholesterol. The molecular mechanisms underlying these health beneficial effects are however not completely elucidated. The aim of this study was to investigate the expression of genes related to lipid metabolism in peripheral blood mononuclear cells (PBMC) depending on the plasma levels of n-6 and n-3 fatty acids and the SFA to PUFA ratio.
2019-03-08 | GSE111567 | GEO
Project description:Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
2019-08-27 | GSE136271 | GEO
Project description:Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
2019-08-27 | GSE136351 | GEO
Project description:Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
2019-08-27 | GSE136278 | GEO
Project description:In the present study, we investigated the consequences of n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic lipid metabolism in mice fed during three months with a diet presenting a high n-6/n-3 PUFA ratio to induce n-3 PUFA depletion. Microarray analyses were performed to identify the molecular targets involved in the development of hepatic steatosis associated with n-3 PUFA depletion. Male C57Bl/6J mice (9 weeks old) were housed in groups of four mice per cage at 22°C in a 12h light/dark cycle and given free access to diet and water. After an acclimatization period of 1 week, the mice were fed a control (CT) or an n-3 PUFA-depleted diet (DEF) for 3 months. At the end of the study period, mice (CT, n=6; DEF, n=7) were anesthetized after a 6h period of fasting. Some mice (CT: n=4 et DEF: n=7) were anesthetized without being starved. A fraction of the main liver lobe was fixed-frozen in isopentane and kept at -80°C for histological analysis. The excess tissue material was immediately clamped in liquid N2 and kept at -80°C. All mice experiments were approved by the local animal ethics committee, and the housing conditions were as specified by the Belgian Law of November 14, 1993 on the protection of laboratory animals (agreement n° LA 1230314).
2011-08-25 | E-GEOD-26986 | biostudies-arrayexpress
Project description:Arabidopsis seeds expressing the castor fatty acid hydroxylase accumulate hydroxylated fatty acids up to 17% of total fatty acids in seed triacylglycerols, however total seed oil is also reduced up to 50%. Investigations into the cause of the reduced oil phenotype through in vivo [14C]acteate and [3H]2O metabolic labeling of developing seeds surprisingly revealed that the rate of de novo fatty acid synthesis within the transgenic seeds was approximately half that of control seeds. Addition of castor phospholipid:diacylglycerol acyltransferase (PDAT) increased hydroxylated fatty acid content of the seed oil, increased the rate of fatty acid synthesis, and mostly restored seed oil levels. RNAseq analysis indicated no changes in expression of fatty acid synthesis genes in hydroxylase-expressing plants. Transcript profiles of Arabidopsis developing seeds of three lines, at three stages of development were generated by deep sequencing, in triplicate, using Illumina.
2014-01-10 | E-GEOD-53952 | biostudies-arrayexpress
Project description:The current study was designed to investigate the circulating miRNA expression signature of dairy cows during several key time points around calving, and under different fatty acids (FA) treatments to get insights into different aspects of metabolic adaptations and their interaction with administrated FA. In this trial, 32 transition Holstein dairy cows were randomly assigned to one of the following treatments: 1-CTRL (n = 8; coconut oil, Bio-Kokosöl #665, Kräuterhaus Sanct Bernhard, KG, Bad Ditzenbach, Germany; 38 and 76 g/d in antepartum (AP) and postpartum (PP)), 2- Essential fatty acids (EFA, n=8, a combination of linseed oil (DERBY® Leinöl #4026921003087, DERBY Spezialfutter GmbH, Münster, Germany; 39 and 78 g/d in AP and PP) and safflower oil (GEFRO Distelöl, GEFRO Reformversand Frommlet KG, Memmingen, Germany; 2 and 4 g/d in AP and PP), 3- conjugated linoleic acid (CLA, n = 8, Lutalin® ; cis-9, trans-11, 10 g/d trans- 10, cis-12 CLA, BASF SE, Lampertheim, Germany; 19 and 38 g/d in AP and PP), and 4- EFA+CLA, a combination of linseed oil, safflower oil and Lutalin® from day 63 AP to day 63 PP. From each cow, four blood samples were collected individually on days -21, +1, +28, and +63 relative to calving, and the plasma fraction was used for RNA extraction. Total RNA was extracted from 128 plasma samples using the QIAGEN miRNeasy serum/plasma kit (Qiagen GmbH, Hilden, Germany), and checked for yield and purity using the small RNA kit on a 2100 Bioanalyzer (Agilent Technologies, Santa Clara, CA, USA). We used the QIAseq miRNA library kit (QIAGEN, Hilden, Germany) for library preparation and Caliper (PerkinElmer, Waltham, MA) for quality check. NGS was performed on the libraries using the NovaSeq 6000 (Illumina, San Diego, CA) setting on single-end 100 bp mode on the respective platform of IGA Technology Services, Udine, Italy (https://igatechnology.com/). Raw-sequencing data was checked for quality (format conversion to FASTQ, demultiplexing, Adapter Trimming, and UMI Remova) using the Illumina Bcl2fastq2 Conversion Software (version 2.20). Detected sequences were analyzed with the miRDeep2 (miRDeep2.pl) software package (version 2.0.0.5) to detect known miRNA and predict putative novel miRNA (using human, ovine, and goat miRNA datasets). MiRDeep2 was fed with the Bos taurus miRNA collection available at miRBase (www.mirbase.org). Read counts for each known and novel miRNA were compiled using the HTSeq-count script. The quantified counts were normalized using the TMM method via the edgeR (version 3.12.0) package in R software (Version 4.0). Only miRNA with at least one count per million over at least 2 samples were taken into consideration for the analysis. Differentially expressed miRNA (DEM) during the time points were identified by performing generalized linear model (GLM) likelihood ratio tests (glmLRT) using the GLM approach in edgeR. The DEMs have been interpreted separately I-during different time points, and also II-between treatments, to gain insight into metabolic and immune adaptation, as well as the role of fatty acids at each time point. A time-affected DEM identified key signaling pathways that are involved in initiating and regulating metabolic shifts during the transition from gestation (non-lactation) to lactation. Although, fatty acid treatments had only minor effects on miRNA expression (insufficient DEM to perform pathway analysis).
2022-08-04 | E-MTAB-11725 | biostudies-arrayexpress
Project description:Arabidopsis seeds expressing the castor fatty acid hydroxylase accumulate hydroxylated fatty acids up to 17% of total fatty acids in seed triacylglycerols, however total seed oil is also reduced up to 50%. Investigations into the cause of the reduced oil phenotype through in vivo [14C]acteate and [3H]2O metabolic labeling of developing seeds surprisingly revealed that the rate of de novo fatty acid synthesis within the transgenic seeds was approximately half that of control seeds. Addition of castor phospholipid:diacylglycerol acyltransferase (PDAT) increased hydroxylated fatty acid content of the seed oil, increased the rate of fatty acid synthesis, and mostly restored seed oil levels. RNAseq analysis indicated no changes in expression of fatty acid synthesis genes in hydroxylase-expressing plants.
2014-01-10 | GSE53952 | GEO