Similar Datasets
Project description:A variety of metabolic disorders are aggravated by obesity. Since mitochondria play key roles in various catabolic and anabolic reactions encompassing lipid metabolism, optimal functioning of mitochondria is critical in preventing various pathologies. Increased amounts of the apolipoprotein O /MIC26 were found in diabetic patients along with lipid accumulation in murine liver upon MIC26 expression. MIC26 is a MICOS complex constituent present in the mitochondrial inner membrane. The functional interplay between MIC26 and cellular metabolome is not understood. Therefore, we employed a multi-omics approach in WT and MIC26 knockout HepG2 cellular models in normoglycemic and hyperglycemic conditions, along with a variety of functional assays. We found that MIC26 is necessary for maintaining glycolysis and lipid metabolism via CPT1A along with cholesterol synthesis in a nutrient-dependent manner. MIC26 deletion led to metabolic rewiring of glutamine utilisation leading us to propose that mitochondrial ultrastructure and cellular metabolome are functionally interdependent.
2023-12-01 | GSE248848 | GEO
Project description:Crizotinib is a first-line targeted therapy against EML4-ALK fusion in non-small cell lung cancer (NSCLC), but the increased resistance limits its clinical application. However, the mechanisms underlying such resistance are largely unexplored. The present study identified ALK protein overexpression in crizotinib-resistant H3122CR cells through immunoblotting. Then, liquid chromatography tandem mass spectrometry-based metabolomics was adopted to investigate metabolic responses. Crizotinib resistance was associated with the reduction of the total lipid content and the increase of organic acid, featuring the upregulation of lipid metabolism. Fatty acid β-oxidation pathway reprogrammed crizotinib-sensitive metabolome to crizotinib-resistant metabolome, resulting in crizotinib resistance. These findings reveal a previously unknown mechanism of crizotinib resistance and suggest promising applications of this approach in prognostic prediction and tailored therapeutics of NSCLC patients.
2021-10-31 | GSE186767 | GEO
Project description:While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence. 14 human and 6 chimpanzee samples were sequenced.
2014-03-31 | E-GEOD-45263 | biostudies-arrayexpress
Project description:Inhibitors of glucose (IO+DHEA group) or fatty acids (ETOMOXIR group) metabolism were applied during bovine oocyte in vitro maturation (IVM). Control group was conducted in standard maturation conditions. In vitro fertilization and embryo culture were applied. Obtained blastocysts were analysed with regard to lipidome, metabolome (mass spectrometry), transcriptome (RNA Seq) and lipid droplets staining (BODIPY).
2023-05-31 | GSE218045 | GEO
Project description:We aim to assess changes in gene expression in the early stages of seedling growth in glyoxylate cycle enzyme knock-outs. The analysis has two clear goals: firstly to discover those genes (and hence enzymes) whose expression changes markedly when a major switch in the pathway of seed lipid mobilisation is imposed, and secondly to use information from metabolome analysis in the same mutants, to discover the impact of well-defined changes in endogenous metabolites on the transcriptome.In wild type seedlings at approximately 2 days post-imbibiton, glyoxylate cycle activity reaches a peak associated with the mobilisation of lipid reserves for the growth of the developing seedling. We have isolated KOs in two enzymes unique to the glyoxylate cycle: malate synthase (ms) and isocitrate lyase (icl). The mutants have a visible seedling phenotype only in the absence of sugar and/or (high) light. Surprisingly, these mutants are able to mobilise their lipid reserves, apparently via a switch from glyoxylate cycle and gluconeogenesis to respiration (Eastmond et al. 2000, PNAS 97: 5669-5674). Transcriptomic analysis will allow us to establish what changes take place in expression of key genes involved in respiration and gluconeogenesis when the glyoxylate cycle is blocked in the KOs. This will in turn provide insights into the pathways of metabolism operating in these plants.In addition we are already in the process of having these mutants analysed by the GARNet metabolomics facility to quantitate changes in organic acids, amino acids and sugars. The use of the transcriptomics facility in parallel will allow us to determine how specific changes in metabolite levels affect the expression of genes involved in carbon and nitrogen metabolism, as well as in seedling development as a whole. One major strength of our approach is that both ms and icl mutants are blocked in the glyoxylate cycle and so will result in many common changes to the metabolome, but each may produce novel changes in specific metabolites which might allow correlation with specific changes in the transcriptome. The joint analysis of metabolome and transcriptome data will be carried out in collaboration with members of our School of Informatics.Whole seedlings will be grown in vitro and harvested 2 days after transfer of imbibed seed to continuous light, and used for RNA extraction. This corresponds to Principle Growth Stage 0.7 in the convention of Boyes et al. (Plant Cell 13; 1499-1510, 2001). Each mutant has a specific wild type control (Columbia in one case and Ws in the other) giving four RNA samples in total.
2005-02-16 | E-NASC-1 | biostudies-arrayexpress
Project description:Whereas all mammals have one glutamate dehydrogenase gene (GLUD1), humans and apes carry an additional gene (GLUD2), which encodes an enzyme with distinct biochemical properties. We inserted human genomic region containing the GLUD2 gene into mice and analyzed the resulting changes in the transcriptome and metabolome during postnatal brain development. Effects were most pronounced early postnatally and affected predominantly genes involved in neuronal development. Remarkably, the effects in the transgenic mice partially parallel the transcriptome and metabolome differences seen between humans and macaques analyzed. Notably, the introduction of GLUD2 did not affect glutamate levels in mice, consistent with observations in the primates. Instead, the metabolic effects of GLUD2 center on the tricarboxylic acid cycle, suggesting that GLUD2 affects carbon flux during early brain development, possibly stimulating lipid biosynthesis.
2016-04-27 | GSE80122 | GEO
Project description:Blood plasma is one of the most commonly analyzed and easily accessible biological samples. Here, we describe an automated liquid-liquid extraction (LLE) platform that generates accurate, precise, and reproducible samples for metabolomic, lipidomic, and proteomic analyses from a single aliquot of plasma while minimizing hands-on time and avoiding contamination from plasticware. We applied mass spectrometry to examine the metabolome, lipidome, and proteome of 90 plasma samples to determine the effects of age, time of day, and a high-fat diet in mice. From 25 μL of mouse plasma, we identified 907 lipid species from 16 different lipid classes and subclasses, 233 polar metabolites, and 344 proteins. We found that the high fat diet induced only mild changes in the polar metabolome, upregulated Apolipoproteins, and induced substantial shifts in the lipidome, including a significant increase in arachidonic acid (AA) and a decrease in eicosapentaenoic acid (EPA) content across all lipid classes.
2025-05-06 | PXD049202 | Pride
Project description:While Neanderthals are extinct, fragments of their genome still persist in the genomes of contemporary humans. Here, we show that such Neanderthal-like sequences are not distributed randomly in contemporary human genomes. Specifically, while genome-wide frequency of Neanderthal-like sites is close to 6% in all out-of-Africa populations, genes involved in lipid catabolism contain large excess Neanderthal-like sequences in Europeans (24.3%), but not in Asians (12.4%). While lipid catabolism cannot be assayed in Neanderthals, we took advantage of genetic divergence between human populations, chimpanzees and Neanderthals to predict metabolic divergence expected from the observed excess of Neanderthal gene flow into Europeans. We confirmed predicted changes in lipid catabolism using hydrophobic metabolome measurements in the brain tissue and further linked these metabolic changes to gene expression divergence.
2014-03-31 | GSE45263 | GEO
Project description:β-catenin signaling can be both a physiological and an oncogenic pathway in the liver. It controls compartmentalized gene expression, allowing the liver to ensure its essential metabolic function. It is activated by mutations in 20 to 40% of hepatocellular carcinomas with specific metabolic features. We decipher the molecular determinants of β-catenin-dependent zonal transcription using mice with β-catenin-activated or -inactivated hepatocytes, characterizing in vivo their chromatin occupancy by Tcf4 and β-catenin, their transcriptome and their metabolome. We find that Tcf4 DNA-bindings depend on β-catenin. Tcf4/β-catenin binds Wnt-responsive elements preferentially around β-catenin-induced genes. In contrast, genes repressed by β-catenin bind Tcf4 on Hnf4-responsive elements. β-catenin, Tcf4 and Hnf4α interact, dictating β-catenin transcription which is antagonistic to that elicited by Hnf4α. Finally, we find the drug/bile metabolism pathway to be the one most heavily targeted by β-catenin, partly through xenobiotic nuclear receptors. We conclude that β-catenin patterns the zonal liver together with Tcf4, Hnf4α and xenobiotic nuclear receptors. This network represses lipid metabolism, and exacerbates glutamine, drug and bile metabolism, mirroring hepatocellular carcinomas with β-catenin mutational activation. In vivo liver samples in 4 conditions: Betacat activated (WCE, Tcf4 chipseq, Betacat chipseq, mRNAseq with 2 replicates), Betacat null (WCE, Tcf4 chipseq, mRNAseq with 2 replicates), Betacat control (mRNAseq with 2 replicates), Wild type (mRNAseq with 2 replicates)
2014-01-18 | E-GEOD-35213 | biostudies-arrayexpress
Project description:Fat metabolism is also peturbed after the diagnosis of type 1 diabetes. Patients have less fat in the liver (4) and increased fasting lipid oxidation (5) compared to controls. Similarly, in a BioBreeding rat model of type 1 diabetes, the diabetes-prone animals develop a reduced respiratory quotient compared to non-diabetic rats before the onset of hyperglycemia, consistent with an increased use of fatty acids relative to carbohydrates as an energy substrate (6). We hypothesized that a lack of insulin reaching the liver contributes to the metabolic shift towards lipid oxidation observed in humans with type 1 diabetes and rodent models of the disease. To test our hypothesis, we measured changes in the hepatic gene expression and serum metabolome of a BioBreeding rat model of type 1 diabetes before and after the onset of hyperglycemia.
2017-06-12 | GSE84886 | GEO