Postnatal hyperglycemia alters amino acid profile in retinas
Ontology highlight
ABSTRACT:
ORGANISM(S): Mouse Mus Musculus
TISSUE(S): Retina
DISEASE(S): Eye Disease
SUBMITTER: 
Zhongjie Fu
PROVIDER: ST002497 | MetabolomicsWorkbench | Thu Feb 16 00:00:00 GMT 2023
REPOSITORIES: MetabolomicsWorkbench
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Project description:Objective: Insulin regulates amino acid metabolism. We investigated whether glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes affect amino acid levels in a large population-based cohort. Subjects and Methods: A total of 9,371 non-diabetic or newly-diagnosed type 2 diabetic Finnish men from the population-based METSIM Study were studied. Proton NMR spectroscopy was used to measure plasma levels of 8 amino acids. Genotyping of 42 SNPs and mRNA microarray analysis from 200 subcutaneous adipose tissue samples were performed. Results: Increasing fasting and/or 2-hour plasma glucose levels were associated with increasing levels of alanine, valine, leucine, isoleucine, phenylalanine and tyrosine, and decreasing levels of histidine and glutamine. We also found significant correlations between insulin sensitivity (Matsuda ISI) and expression of genes regulating amino acid metabolism. Only one SNP (rs780094 in GCKR) of the 42 risk SNPs for type 2 diabetes or hyperglycemia was significantly associated with the levels of alanine, isoleucine, and glutamine. Conclusions : We observed that the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia. These associations seemed to be mediated by insulin resistance, at least in part. GCKR rs780094 was significantly associated with several amino acids. Total RNA was obtained from subcutaneous fat biopsies from 200 people participating in the METSIM study (4 samples were replicated for a total of 204 arrays).
2012-04-01 | E-GEOD-32512 | biostudies-arrayexpress
Project description:Objective: Insulin regulates amino acid metabolism. We investigated whether glycemia and 43 genetic risk variants for hyperglycemia/type 2 diabetes affect amino acid levels in a large population-based cohort. Subjects and Methods: A total of 9,371 non-diabetic or newly-diagnosed type 2 diabetic Finnish men from the population-based METSIM Study were studied. Proton NMR spectroscopy was used to measure plasma levels of 8 amino acids. Genotyping of 42 SNPs and mRNA microarray analysis from 200 subcutaneous adipose tissue samples were performed. Results: Increasing fasting and/or 2-hour plasma glucose levels were associated with increasing levels of alanine, valine, leucine, isoleucine, phenylalanine and tyrosine, and decreasing levels of histidine and glutamine. We also found significant correlations between insulin sensitivity (Matsuda ISI) and expression of genes regulating amino acid metabolism. Only one SNP (rs780094 in GCKR) of the 42 risk SNPs for type 2 diabetes or hyperglycemia was significantly associated with the levels of alanine, isoleucine, and glutamine. Conclusions : We observed that the levels of branched-chain, aromatic amino acids and alanine increased and the levels of glutamine and histidine decreased with increasing glycemia. These associations seemed to be mediated by insulin resistance, at least in part. GCKR rs780094 was significantly associated with several amino acids.
2012-04-02 | GSE32512 | GEO
Project description:For the first time in Lactococcus lactis, amino acid starvation response was characterized. The natural imposition of isoleucine starvation, by its consumption during growth, associated to transcript profiling, allowed defining exhaustively this stress stimulon. It consisted of a general induction of nitrogen metabolism (amino acid biosynthesis and transport, proteolytic system and proteases), a strong repression of genes encoding major physiological activities (translation, transcription, carbon metabolism, purine and pyrimidine biosynthesis and fatty acid metabolism) and the induction of unexpected cross responses to acid, osmotic and oxidative stresses. Keywords: stress response, time course Isoleucine starvation was imposed by the consumption of this amino acid during the growth of Lactococcus lactis IL1403 on ILV0.1 medium (CDM with ten-fold reduced concentrations of isoleucine, leucine and valine) and under controlled conditions (30 °C, pH 6.6, nitrogen atmosphere). Cell samples were harvested in exponential phase and after 30 min, 1.7 h and 3.5 h of isoleucine starvation. Total RNA was extracted from these samples and radiolabelled cDNA were prepared and hybridized on nylon arrays. 2053 amplicons specific of Lactococcus lactis IL1403 genes were spotted twice on the array. The 4 time-points were analyzed simultaneously and 3 independent repetitions were performed.
2010-06-25 | E-GEOD-4872 | biostudies-arrayexpress
Project description:CodY is a nutritional regulator mainly involved in amino acid metabolism. It has been extensively studied in Bacillis subtilis and Lactococcus lactis. We investigated the role of CodY in gene regulation and virulence of the human pathogen Streptococcus pneumoniae. We constructed a codY-mutant and examined the effect on gene and protein expression by microarray and 2D DIGE analysis. The pneumococcal CodY-regulon was found to consist predominantly of genes involved in amino acid metabolism, but also several other cellular processes, such as carbon metabolism and iron uptake. By means of electrophoretic mobility shift assays and DNA footprinting, we showed that most targets identified are under direct control of CodY. By mutating DNA predicted to represent the CodY-box based on the L. lactis consensus, we demonstrated that this sequence is indeed required for in vitro DNA-binding to target promoters. Similar to L. lactis, DNA-binding of CodY was enhanced in the presence of the branched chain amino acids isoleucine, leucine, and valine, and not by GTP. We observed in experimental mouse models that CodY is transcribed in the murine nasopharynx and lungs, and is specifically required for colonization. This finding was underscored by the diminished ability of the codY-mutant to adhere to nasopharyngeal cells in vitro. In conclusion, pneumococcal CodY predominantly regulates genes involved in amino acid metabolism and contributes to the early stages of infection, i.e. colonization of the nasopharynx. Keywords: codY CodY of Streptococcus pneumoniae: link between nutritional gene regulation and virulence
2010-05-25 | E-GEOD-7350 | biostudies-arrayexpress
Project description:There is a gap in our understanding of the protective effect of the essential ω-3 long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) on proliferative retinopathies. In retinopathy of prematurity (ROP), DHA supplementation alone may not reduce the risk for severe disease. We found that in mouse neonates with hyperglycemia-associated retinopathy (HAR) with impaired retinal vessel growth modeling Phase I ROP versus controls, there was a strong metabolic shift in almost all types of retinal neuronal cells identified with single-cell transcriptomics. Loss of adiponectin (Apn-/-), modeling low APN seen in premature infants, caused a ω-3 and ω-6 LCPUFA imbalance in HAR mouse retinas. Dietary intake of ω-3 vs ω-6 LCPUFA promoted retinal vessel growth, associated with increased APN levels and increased retinal APN receptor AdipoR1 gene expression. Interestingly, we found that ω-6 vs. ω-3 LCPUFA was essential in maintaining retinal metabolism and neuronal development. Our findings suggest that both ω-3 and ω-6 LCPUFA are essential in protecting against retinal neurovascular dysfunction in Phase I ROP model. Maintaining adequate ω-6 LCPUFA levels is required while supplementing ω-3 LCPUFA to prevent retinopathy.
2022-04-20 | GSE198785 | GEO
Project description:Transcription profiling of wild type, relA-, and relA-spoT-, crp-, dksA-, rpoS-, lrp- mutant strains of E. coli starved for isoleucine Bacteria comprehensively reorganize their global gene expression when faced with nutrient exhaustion. In Escherichia coli and other free-living bacteria, the alarmone ppGpp facilitates this massive response by directly or indirectly coordinating the down-regulation of genes of the translation apparatus, and the induction of biosynthetic genes and the general stress response. Such a large reorientation likely requires the cooperative activities of many different genetic regulators, yet the structure of the transcription network below the level of ppGpp remains poorly defined. Using isoleucine starvation as an experimental model system for amino acid starvation, we identified genes that required ppGpp, Lrp, and RpoS for their induction. Surprisingly, despite the fact that the overwhelming majority of genes controlled by Lrp and RpoS required ppGpp for their activation, we found that these two regulons were not induced simultaneously. The data reported here suggest that metabolic genes, such as those of the Lrp regulon, require only a low basal level of ppGpp for their efficient induction. In contrast, the RpoS-dependent general stress response is not robustly induced until relatively high levels of ppGpp accumulate. Here we describe a data-driven conceptual model that explains how bacterial cells allocate transcriptional resources between metabolic and stress survival processes by discretely tuning regulatory activities to a central indicator of cellular physiology. The regulatory structure that emerges is consistent with a rheostatic model of the stringent response that allows cells to efficiently adapt to a wide range of nutritional environments. Keywords: genetic modification design; stress response; isoleucine starvation Two experiments were run. First experiment: WT and several mutant strains were starved for isoleucine (exhaustion of 60 uM ile). 40 minutes after starvation, RNA was extracted. All samples were compared to RNA from rapidly growing WT cells in identical medium replete with isoleucine (400 uM). 16 samples were hybridized: duplicates of 8 strains/conditions. Wildtype in log phase (OD = 0.4) with replete ile was control for ile starved samples. Second experiment: WT strain was starved for isoleucine (exhaustion of 60 uM ile). RNA was extracted at 12 timepoints as the cells entered stationary phase. All samples were compared to RNA from rapidly growing WT cells in identical medium replete with isoleucine (400 uM). 14 samples were hybridized: duplicates of the control condition and single timepoints during starvation. Wildtype in log phase (OD = 0.4) with replete ile was control for ile starved samples.
2008-04-08 | E-GEOD-11087 | biostudies-arrayexpress
Project description:Isoleucine (Ile) is one of the branched-chain amino acids (BCAAs) that are essential substrates for protein synthesis in all organisms. In this study, we characterized an Arabidopsis mutant, lib (low isoleucine biosynthesis), that has defects in both cell proliferation and cell expansion processes during root development. This mutant carries a mutation in OMR1 gene that encodes a threonine deaminase/dehydratase (TD) which results in a defect in isoleucine production. Microarray analysis indicated that the partial deficiency of Ile in the lib mutant triggers a decrease in transcript levels of the genes encoding the major enzymes involved in the BCAA degradation pathway; the analysis also indicated that many genes involved in the biosynthesis of methionine-derived glucosinolates are up-regulated.
2012-11-07 | GSE42060 | GEO
Project description:Amino acid assimilation and metabolism are crucial for bacterial growth and survival and this is particularly obvious for lactic acid bacteria (LAB) that are generally auxotroph for various amino acids. However, amino acid assimilation is poorly characterized and a complete description of the response during amino acid starvation is still lacking in LAB. In this context, the global response of the LAB model Lactococcus lactis was characterized during isoleucine starvation in batch culture. The stress was imposed by isoleucine natural consumption in an initially rich chemically defined medium. Dynamic analyses were performed both using transcriptomic and proteomic approaches. The response was found to occur gradually and could be divided into three major parts that were firstly deduced from transcriptomic analysis and generally corroborated by proteomic results: (i) a global repression of biogenic processes (transcription, translation, and carbon metabolism and transport), (ii) a specific response related to the limiting nutrient (numerous pathways belonging to carbon or nitrogen metabolism and leading to isoleucine supply were activated) and (iii) an additional response connected to oxidative stress (induction of aerobic metabolism, electron transport, thioredoxin metabolism and pyruvate dehydrogenase). The involvement of various regulatory mechanisms such as growth rate regulation, stringent response, CodY, GlnR, and CcpA regulations, was discussed on the basis of transcriptomic data comparisons. Above the full description of L. lactis isoleucine starvation response, this work additionally provided a complex but realistic outlook of the regulation network involved in isoleucine starvation. Such integrated and comparative approach will allow, by its implementation to other regulations and environmental conditions, the whole regulatory network of L. lactis or any other microorganism to be deciphered. Batch cultivation of Lactococcus lactis IL1403 were carried out on a chemically defined medium and under controlled conditions (30 °C, pH 6.6, nitrogen atmosphere). Cell samples were harvested at steady state. Total RNA was extracted from these samples and radiolabelled cDNA were prepared and hybridized on nylon arrays. 1948 amplicons specific of Lactococcus lactis IL1403 genes were spotted twice on the array. Samples corresponding to various growth rates were analyzed simultaneously and 3 independent repetitions were performed.
2011-09-21 | E-GEOD-12962 | biostudies-arrayexpress
Project description:<p>N-3 polyunsaturated fatty acids (PUFAs) may prevent retinal vascular abnormalities observed in oxygen-induced retinopathy, a model of retinopathy of prematurity (ROP). In the OmegaROP prospective cohort study, we showed that preterm infants who will develop ROP accumulate the n-6 PUFA arachidonic acid (ARA) at the expense of the n-3 PUFA docosahexaenoic acid (DHA) in erythrocytes with advancing gestational age (GA). As mice lacking plasmalogens ―that are specific phospholipids considered as reservoirs of n-6 and n-3 PUFAs― display a ROP-like phenotype, the aim of this study was to determine whether plasmalogens are responsible for the changes observed in subjects from the OmegaROP study. Accordingly, preterm infants aged less than 29 weeks GA were recruited at birth in the Neonatal Intensive Care Unit of University Hospital Dijon, France. Blood was sampled very early after birth to avoid any nutritional influence on its lipid composition. The lipid composition of erythrocytes and the structure of phospholipids including plasmalogens were determined by global lipidomics using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). LC-HRMS data confirmed our previous observations by showing a negative association between the erythrocyte content in phospholipid esterified to n-6 PUFAs and GA in infants without ROP (rho = -0.485, p = 0.013 and rho = -0.477, p = 0.015 for ethanolamine and choline total phospholipids, respectively). Phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) species with ARA, namely PtdCho16:0/20:4 (rho = -0.511, p < 0.01) and PtdEtn18:1/20:4 (rho = -0.479, p = 0.015), were the major contributors to the relationship observed. On the contrary, preterm infants developing ROP displayed negative association between PtdEtn species with n-3 PUFAs and GA (rho = -0.380, p = 0.034). They were also characterized by a positive association between GA and the ratio of ethanolamine plasmalogens (PlsEtn) with n-6 PUFA to PlsEtn with n-3 PUFAs (rho = 0.420, p = 0.029), as well as the ratio of PlsEtn with ARA to PlsEtn with DHA (rho = 0.843, p = 0.011). Altogether, these data confirm the potential accumulation of n-6 PUFAs with advancing GA in erythrocytes of infants developing ROP. These changes may be partly due to plasmalogens.</p>
2022-09-07 | MTBLS4219 | MetaboLights