scholarly journals Proteomic And Metabolomic Analyses Reveal The Full Spectrum of Inflammatory and Lipid Metabolic Abnormalities In Dyslipidemia

2020 ◽  
Author(s):  
Hui DU ◽  
Yifei RAO ◽  
Ronghua LIU ◽  
Kesui DENG ◽  
Yongmei GUAN ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Metabolic Pathways ◽  
Inflammatory Responses ◽  
Arachidonic Acid Metabolism ◽  
Antioxidant Defenses ◽  
Alpha Linolenic Acid ◽  
Full Spectrum ◽  
Potential Biomarker

Abstract Background: Dyslipidemia is a common, chronic metabolic disease associated with cardiovascular complications. Due to the multiplicity of etiological factors, the pathogenesis of dyslipidemia is still unclear.Methods: In this study, we combined proteomics and metabolomics methods to analyze the plasma of patients with dyslipidemia and healthy subjects. ITRAQ markers, combined with LC-MS/MS proteomics technology and the UHPLC/ Orbitfast-X Tribrid system, were used to establish the metabolite profile in clinical dyslipidemia.Results: A total of 137 differentially expressed proteins were identified, mainly related to biological processes such as protein activation cascades, adaptive immune responses, complement activation, acute inflammatory responses and regulation of acute inflammatory responses. These proteins are involved in the regulation of important metabolic pathways, such as immunity and inflammation, coagulation and hemostasis, lipid metabolism, and oxidation and antioxidant defenses. Analysis of clinical metabolites showed there were 69 different metabolites in plasma, mainly related to glycerolipid, sphingolipid, porphyrin, alpha-linolenic acid, linoleic acid and arachidonic acid metabolism, suggesting that regulation of inflammation and lipid metabolism may be disturbed in patients with dyslipidemia. Among these, significant changes were observed in indole-3-propionic acid (IPA), which is considered a potential biomarker of dyslipidemia. Conclusions: Combined analysis of proteins and metabolites showed that arachidonic acid, linoleic acid and lipid metabolic pathways were closely related to dyslipidemia. IPA may be a potential biomarker.The information provided in this study may provide new insights into the pathogenesis of dyslipidemia and related diseases, as well as potential intervention targets.

scholarly journals Mechanism of Curcuma wenyujin Rhizoma on Acute Blood Stasis in Rats Based on a UPLC-Q/TOF-MS Metabolomics and Network Approach

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 82 ◽  
Author(s):  
Min Hao ◽  
De Ji ◽  
Lin Li ◽  
Lianlin Su ◽  
Wei Gu ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Lipid Metabolism ◽  
Linoleic Acid ◽  
Acid Metabolism ◽  
Blood Stasis ◽  
Arachidonic Acid Metabolism ◽  
Sphingolipid Metabolism ◽  
Network Pharmacology ◽  
Therapeutic Mechanism ◽  
Linoleic Acid Metabolism

Rhizome of Curcuma wenyujin, which is called EZhu in China, is a traditional Chinese medicine used to treat blood stasis for many years. However, the underlying mechanism of EZhu is not clear at present. In this study, plasma metabolomics combined with network pharmacology were used to elucidate the therapeutic mechanism of EZhu in blood stasis from a metabolic perspective. The results showed that 26 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees by EZhu preadministration. Metabolic pathway analysis showed that the improvement of blood stasis by Curcuma wenyujin rhizome was mainly related to lipid metabolism (linoleic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism) and amino acid metabolisms (tryptophan metabolism, lysine degradation). The component-target-pathway network showed that 68 target proteins were associated with 21 chemical components in EZhu. Five metabolic pathways of the network, including linoleic acid metabolism, sphingolipid metabolism, glycerolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis, were consistent with plasma metabolomics results. In conclusion, plasma metabolomics combined with network pharmacology can be helpful to clarify the mechanism of EZhu in improving blood stasis and to provide a literature basis for further research on the therapeutic mechanism of EZhu in clinical practice.

scholarly journals High-Throughput Untargeted Serum Metabolomics Analysis of Hyperuricemia Patients by UPLC-Q-TOF/MS

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Nankun Qin ◽  
Yue Jiang ◽  
Wenjun Shi ◽  
Liting Wang ◽  
Lingbo Kong ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Sphingolipid Metabolism ◽  
Tryptophan Biosynthesis ◽  
Linoleic Acid Metabolism ◽  
Phenylalanine Metabolism ◽  
Tof Ms

Hyperuricemia (HUA) as a metabolic disease is closely associated with metabolic disorders. The etiology and pathogenesis of HUA are not fully understood, so there is no radical cure so far. Metabolomics, a specialized study of endogenous small molecule substances, has become a powerful tool for metabolic pathway analysis of selected differential metabolites, which is helpful for initially revealing possible development mechanisms of various human diseases. Twenty HUA patients and 20 healthy individuals participated in the experiment, and ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was employed to investigate serum samples to find differential metabolites. The statistical techniques used were principal component analysis and orthogonal partial least-squares discriminant analysis. The differences in metabolomics results of samples after pretreatment with different solvents were compared, 38, 20, 26, 28, 33, 50, and 40 potential differential metabolites were found, respectively, in HUA patient samples, and each group involved different metabolic pathways. Repetitive metabolites were removed, 138 differential metabolites in HUA serum were integrated for analysis, and the human body was affected by 7 metabolic pathways of glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and α-linolenic acid metabolism. In this work, the metabolomics approach based on UPLC-Q-TOF/MS was employed to investigate serum metabolic changes in HUA patients, 138 potential differential metabolites related to HUA were identified, which provided associations of lipids, amino acids, fatty acids, organic acids, and nucleosides profiles of HUA individuals. Metabolic pathways involved in glycerophospholipid metabolism, sphingolipid metabolism, arachidonic acid metabolism, linoleic acid metabolism, phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and a-linolenic acid metabolism shed light on the understanding of the etiology and pathogenesis process of HUA.

scholarly journals Metabolic Profiling Revealed Dysregulated Arachidonic Acid Metabolism and Tryptophan Metabolism in the Lungs from Canines with Pacing-induced Heart Failure

2020 ◽  
Author(s):  
Junhan Zhao ◽  
Jing Wang ◽  
Shengwen Yang ◽  
Ran Jing ◽  
Xi Liu ◽  
...  
Keyword(s):  
Heart Failure ◽  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Sham Group ◽  
Acid Metabolism ◽  
Congestion Management ◽  
Arachidonic Acid Metabolism ◽  
Tryptophan Metabolism ◽  
Negative Ion ◽  
Metabolic Signatures

Abstract Background: Lung has critical pathophysiological connections to heart and lung congestion presents one of the hallmark features of heart failure (HF). This study aimed to explore the metabolic signatures and disturbances in lungs under HF condition and provide insights on the pathophysiology of the lungs under HF condition from the perspective of metabolism.Methods: In this study, we established a rapid pacing induced HF canine model and applied a comprehensive untargeted metabolomics method to comparatively assessed the metabolomics profiles in the lung tissues from HF group and sham group. Results: Distinct metabolic signatures were identified in the lungs between beagles in HF group and sham group. 81 dysregulated metabolites were identified as differential metabolites (adjusted P <0.05, FC≥2 or≤0.5) in positive ion mode and 80 dysregulated metabolites in negative ion mode, indicating a profound metabolic alteration in the lungs under HF condition. In pathway analysis, arachidonic acid metabolism and tryptophan metabolism were identified as the most significant dysregulated metabolic pathways in the lungs from HF beagles.Conclusions: In this study, we identified profound metabolic variation and dysregulated metabolic pathways, which may deepen our understanding on the pathophysiology of the lungs under HF condition from the perspective of metabolism and open new avenues in lung congestion management in HF.

scholarly journals Level of Arachidonic Acid and State of Peroxidation Processes in Patients with Aspirin-Intolerant Polypous Rhinosinusitis

2016 ◽  
Vol 23 (4) ◽  
pp. 2016410
Author(s):  
Ivanna Koshel
Keyword(s):  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Serum Proteins ◽  
Arachidonic Acid Metabolism ◽  
Oxidative Modification ◽  
Key Enzyme ◽  
Protein Peroxidation ◽  
Genetic Block ◽  
Peroxidation Processes

The main peculiarity of aspirin-intolerant polypous rhinosinusitis pathogenesis is the presence of “genetic block” of constitutive cyclooxygenase being the key enzyme of the arachidonic acid metabolism. It justifies the necessity of studying its metabolic peculiarities.The objective of the research was to determine the level of arachidonic acid as well as the state of lipid and protein peroxidation processes in patients with aspirin-intolerant polypous rhinosinusitis.Materials and methods. The levels of arachidonic acid, malondialdehyde and oxidative modification of serum proteins were studied in 20 patients with aspirin-intolerant polypous rhinosinusitis and 7 healthy individuals.Results. Significantly elevated levels of arachidonic levels were observed. The search for alternative metabolic pathways stimulated lipid and protein peroxidation processes and led to the increase in the levels of malondialdehyde and oxidative modification of serum proteins. The peculiarities of biochemical changes indicated pro-inflammatory orientation of lipid metabolism.Conclusions. The obtained data confirmed the hypothesis of “genetic block” of the arachidonic acid metabolism as the main pathogenetic component of aspirin-intolerant polypous rhinosinusitis and allowed us to clearly interpret biochemical picture of the disease.

Metabolomic Signature of Patients With Narcolepsy

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000013128
Author(s):  
Dauvilliers Yves ◽  
Lucie Barateau ◽  
Benita Middleton ◽  
Daan Van Der Veen ◽  
Debra J Skene
Keyword(s):  
Arachidonic Acid ◽  
Metabolic Pathways ◽  
Slow Wave Sleep ◽  
Arachidonic Acid Metabolism ◽  
Metabolic Phenotype ◽  
Metabolic Disturbances ◽  
Brain Disorder ◽  
Metabolite Concentrations ◽  
Obese Subjects

Background and Objective:Narcolepsy type 1 (NT1) is an orphan brain disorder caused by the irreversible destruction of orexin neurons. Metabolic disturbances are common in patients with NT1 who have a body mass index (BMI) 10-20% higher than the general population, with one third being obese (BMI>30 kg/m2). Besides the destruction of orexin neurons in NT1, the metabolic alterations in obese and non-obese patients with narcolepsy type 1 remain unknown. The aim of the study was to identify possible differences in plasma metabolic profiles between patients with NT1 and controls as a function of their BMI status.Methods:We used a targeted liquid chromatography-mass spectrometry metabolomics approach to measure 141 circulating, low molecular weight metabolites in drug-free fasted plasma samples from 117 NT1 patients (including 41 obese subjects) compared with 116 BMI-matched controls (including 57 obese subjects).Results:Common metabolites driving the difference between NT1 and controls, irrespective of BMI, were identified, namely sarcosine, glutamate, nonaylcarnitine (C9), 5 long chain lysophosphatidylcholine acyls, one sphingolipid, 12 phosphatidylcholine diacyls and 11 phosphatidylcholine acyl-akyls, all showing increased concentrations in NT1. Metabolite concentrations significantly affected by NT1 (n = 42) and BMI category (n = 40) showed little overlap (n = 5). Quantitative enrichment analysis revealed common metabolic pathways that were implicated in the NT1/control differences, in both normal BMI and obese comparisons, namely glycine and serine, arachidonic acid, and tryptophan metabolisms. The metabolites driving these differences were glutamate, sarcosine and ornithine (glycine and serine metabolism), glutamate and PC aa C34:4 (arachidonic acid metabolism) and glutamate, serotonin and tryptophan (tryptophan metabolism). Linear metabolite-endophenotype regression analyses highlight that as part of the NT1 metabolic phenotype, most of the relationships between the sleep parameters (i.e. slow wave sleep duration, sleep latency and periodic leg movement) and metabolite concentrations seen in the controls were lost.Discussion:These results represented the most comprehensive metabolic profiling of patients with NT1 as a function of BMI and propose some metabolic diagnostic biomarkers for NT1, namely glutamate, sarcosine, serotonin, tryptophan, nonaylcarnitine and some phosphatidylcholines. The metabolic pathways identified offer, if confirmed, possible targets for treatment of obesity in NT1.Classification of Evidence:This study provides Class II evidence that a distinct metabolic profile can differentiate patients with Narcolepsy Type 1 from patients without the disorder.

scholarly journals Combined signature of rumen microbiome and metabolome in dairy cows with different feed intake levels

2020 ◽  
Vol 98 (3) ◽  
Author(s):  
Yeqing Q Li ◽  
Yumeng M Xi ◽  
Zedong D Wang ◽  
Hanfang F Zeng ◽  
Zhaoyu Han
Keyword(s):  
Linoleic Acid ◽  
Dairy Cows ◽  
Linolenic Acid ◽  
Relative Abundance ◽  
Feed Intake ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Ruminal Fermentation ◽  
Alpha Linolenic Acid ◽  
Rumen Microbiome

Abstract Feed intake is a major factor in maintaining the balance between ruminal fermentation and the microbial community of dairy cows. To explore the relationship among feed intake, microbial metabolism, and ruminal fermentation, we examined the combined signatures of the microbiome and metabolome in dairy cows with different feed intake levels. Eighteen dairy cows were allocated to high feed intake (HFI), medium feed intake (MFI), and low feed intake (LFI) groups according to their average daily feed intake. 16S rDNA sequencing results revealed that the relative abundance of Firmicutes in the HFI group was significantly higher than that in the MFI and LFI groups (P &lt; 0.05). The ratio of Bacteroidetes to Firmicutes was significantly lower in the HFI group than in the MFI and LFI groups (P &lt; 0.05). The relative abundance of Lachnospiraceae_unclassified, Veillonellaceae_unclassified, and Saccharofermentants was significantly higher in the HFI group than in the LFI and MFI groups (P &lt; 0.05). The relative abundance of Erysipelotrichaceae_unclassified and Butyrivibrio was significantly higher in the HFI group than in the MFI and LFI groups (P &lt; 0.05). Ultra high performance liquid chromatography-mass spectrometry revealed five key pathways, including the linoleic acid metabolism pathway, alpha-linolenic acid metabolism, arginine and proline metabolism, glutathione metabolism, and valine, leucine, and isoleucine biosynthesis, which are closely related to energy and amino acid metabolism. Linoleic acid, glutamate, alpha-linolenic acid, l-methionine, and l-valine levels were significantly lower in the HFI group than in the MFI and LFI groups (q &lt; 0.05), while the relative content of glutamate was significantly lower in the MFI group than in the LFI group (q &lt; 0.05). Stearic acid content was significantly higher in the HFI group than in the LFI group (q &lt; 0.05). Our findings provide insight into the rumen microbiome of dairy cows with different feed intake and the metabolic pathways closely associated with feed intake in early-lactating cows. The candidates involved in these metabolic pathways may be useful for identifying variations in feed intake. The signatures of the rumen microbiome and metabolome in dairy cows may help make decisions regarding feeding.

scholarly journals Lomatogonium Rotatum for Treatment of Acute Liver Injury in Mice: A Metabolomics Study

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 227 ◽  
Author(s):  
Renhao Chen ◽  
Qi Wang ◽  
Lanjun Zhao ◽  
Shilin Yang ◽  
Zhifeng Li ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Liver Injury ◽  
Acid Metabolism ◽  
Acute Liver Injury ◽  
Tca Cycle ◽  
Arachidonic Acid Metabolism ◽  
Hepatoprotective Effect ◽  
Metabolomics Study ◽  
Metabolomics Analysis

Lomatogonium rotatum (L.) Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl4-induced acute liver injury through conventional assays and metabolomics analysis. This study consisted of male mice (n = 23) in four groups (i.e., control, model, positive control, and LR). The extract of whole plant of LR was used to treat mice in the LR group. Biochemical and histological assays (i.e., serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and histological changes of liver tissue) were used to evaluate LR efficacy, and metabolomics analysis based on GC-MS and LC-MS was conducted to reveal metabolic changes. The conventional analysis and metabolomic profiles both suggested that LR treatment could protect mice against CCl4-induced acute liver injury. The affected metabolic pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, CoA biosynthesis, glycerophospholipid metabolism, the TCA cycle, and purine metabolism. This study identified eight metabolites, including phosphopantothenic acid, succinic acid, AMP, choline, glycerol 3-phosphate, linoleic acid, arachidonic acid, and DHA, as potential biomarkers for evaluating hepatoprotective effect of LR. This metabolomics study may shed light on possible mechanisms of hepatoprotective effect of LR.

Cytosolic phospholipase A2α regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation

2005 ◽  
Vol 288 (6) ◽  
pp. R1774-R1782 ◽  
Author(s):  
Adam Sapirstein ◽  
Hideyuki Saito ◽  
Sarah J. Texel ◽  
Tarek A. Samad ◽  
Eileen O’Leary ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Responses ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase 2 ◽  
Phospholipase A ◽  
Wild Type ◽  
Cytosolic Phospholipase ◽  
The Central Nervous System ◽  
Cox 2 ◽  
The Brain

The products of arachidonic acid metabolism are key mediators of inflammatory responses in the central nervous system, and yet we do not know the mechanisms of their regulation. The phospholipase A2 enzymes are sources of cellular arachidonic acid, and the enzymes cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) are essential for the synthesis of inflammatory PGE2 in the brain. These studies seek to determine the function of cytosolic phospholipase A2α (cPLA2α) in inflammatory PGE2 production in the brain. We wondered whether cPLA2α functions in inflammation to produce arachidonic acid or to modulate levels of COX-2 or mPGES-1. We investigated these questions in the brains of wild-type mice and mice deficient in cPLA2α (cPLA2α−/−) after systemic administration of LPS. cPLA2α−/− mice had significantly less brain COX-2 mRNA and protein expression in response to LPS than wild-type mice. The reduction in COX-2 was most apparent in the cells of the cerebral blood vessels and the leptomeninges. The brain PGE2 concentration of untreated cPLA2α−/− mice was equal to their wild-type littermates. After LPS treatment, however, the brain concentration of PGE2 was significantly less in cPLA2α−/− than in cPLA2α+/+ mice (24.4 ± 3.8 vs. 49.3 ± 11.6 ng/g). In contrast to COX-2, mPGES-1 RNA levels increased equally in both mouse genotypes, and mPGES-1 protein was unaltered 6 h after LPS. We conclude that cPLA2α regulates COX-2 levels and modulates inflammatory PGE2 levels. These results indicate that cPLA2α inhibition is a novel anti-inflammatory strategy that modulates, but does not completely prevent, eicosanoid responses.

scholarly journals Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

2016 ◽  
Vol 54 (6) ◽  
pp. 4303-4315 ◽  
Author(s):  
Ameer Y. Taha ◽  
Helene C. Blanchard ◽  
Yewon Cheon ◽  
Epolia Ramadan ◽  
Mei Chen ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Dietary Linoleic Acid

scholarly journals Integrating 3-omics data analyze rat lung tissue of COPD states and medical intervention by delineation of molecular and pathway alterations

2017 ◽  
Vol 37 (3) ◽  
Author(s):  
Jiansheng Li ◽  
Peng Zhao ◽  
Liping Yang ◽  
Ya Li ◽  
Yange Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Arachidonic Acid ◽  
Energy Metabolism ◽  
Molecular Mechanisms ◽  
Acid Metabolism ◽  
Inflammatory Responses ◽  
Medical Intervention ◽  
Arachidonic Acid Metabolism ◽  
Chronic Obstructive ◽  
Therapeutic Effects

Chronic obstructive pulmonary disease (COPD) is a serious health problem. However, the molecular pathogenesis of COPD remains unknown. Here, we explored the molecular effects of cigarette smoke and bacterial infection in lung tissues of COPD rats. We also investigated therapeutic effects of aminophylline (APL) on the COPD rats and integrated transcriptome, proteome, and metabolome data for a global view of molecular mechanisms of COPD progression. Using molecular function and pathway analyses, the genes and proteins regulated in COPD and APL-treated rats were mainly attributed to oxidoreductase, antioxidant activity, energy and fatty acid metabolism. Furthermore, we identified hub proteins such as Gapdh (glyceraldehyde-3-phosphate dehydrogenase), Pkm (pyruvate kinase isozymes M1/M2), and Sod1 (superoxide dismutase 1), included in energy metabolism and oxidative stress. Then, we identified the significantly regulated metabolic pathways in lung tissues of COPD- and APL-treated rats, such as arachidonic acid, linoleic acid, and α-linolenic acid metabolism, which belong to the lipid metabolism. In particular, we picked the arachidonic acid metabolism for a more detailed pathway analysis of transcripts, proteins, and metabolites. We could observe an increase in metabolites and genes involved in arachidonic acid metabolism in COPD rats and the decrease in these in APL-treated rats, suggesting that inflammatory responses were up-regulated in COPD rats and down-regulated in APL-treated rats. In conclusion, these system-wide results suggested that COPD progression and its treatment might be associated with oxidative stress, lipid and energy metabolism disturbance. Additionally, we demonstrated the power of integrated omics for the elucidation of genes, proteins, and metabolites’ changes and disorders that were associated with COPD.

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