A Urinary Metabolomics Analysis Based on UPLC-MS and Effects of Moxibustion in APP/PS1 Mice

Background: Alzheimer's disease (AD) is a common neurodegenerative disorder with the symptoms of cognitive impairment and decreased learning and memory abilities. Metabolomics can reflect the related functional status and physiological and pathological changes in the process of AD. Moxibustion is a unique method in traditional Chinese medicine, which has been used in the treatment and prevention of diseases for thousands of years. Methods: A total of 32 APP/PS1 mice were randomly divided into the model group, moxibustion group, moxa smoke group and smoke-free moxibustion group (n=8/group), using the random number table method, while eight C57BL/6 mice were used as the control group. The five groups were measured for 20 min/day, 6 days/week, for 4 weeks. After 4 weeks’ experiment, all the mice were placed in metabolic cages to collect urine continuously for 24 hours, for UPLC-MS analysis. Results: Principal component analysis (PCA) was used to identify the different metabolites among the five groups, and partial least squares discriminant analysis (PLS-DA) was performed to reveal the effects on the metabolic variance. Sixteen potential biomarkers were identified among the five groups, primarily related to amino acid metabolism, starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, and aminoacyl biosynthesis. There were 17 differences in the potential metabolites between the control and model groups, involving the metabolism of amino acid, purine, pyrimidine, nicotinic acid and nicotinamide, and biosynthesis of pantothenate and coenzyme A. Fifteen potential biomarkers were identified between the model and moxibustion groups, related to starch metabolism, sucrose metabolism, interconversion of pentose and glucuronate, glyoxylate, dicarboxylate anions and some amino acid metabolism. Conclusion: Moxibustion can regulate the metabolism of substance and energy by improving the synthesis and decomposition of carbohydrates and amino acids in APP/PS1 transgenic AD model mice.

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Aromatic amino acid metabolism of neonatal piglets receiving TPN: effect of tyrosine precursors

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.5.e672 ◽

1994 ◽

Vol 267 (5) ◽

pp. E672-E679 ◽

Cited By ~ 3

Author(s):

L. J. Wykes ◽

J. D. House ◽

R. O. Ball ◽

P. B. Pencharz

Keyword(s):

Amino Acid ◽

Aromatic Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Central Line ◽

High Plasma ◽

Control Group ◽

Neonatal Piglets ◽

Aromatic Amino Acid Metabolism ◽

Plasma Tyrosine

Low tyrosine solubility in total parenteral nutrition (TPN) solutions complicates meeting the aromatic amino acid needs of infants. This study compared the effectiveness of two tyrosine precursors to supply the aromatic amino acid needs of TPN-fed neonatal piglets with a control group in which total aromatic acid needs were met by the addition of phenylalanine (Phe). Eighteen 3-day-old male Yorkshire piglets (6/group) received TPN for 8 days by central line. The solution was supplemented with Phe or one of the following two tyrosine precursors: N-acetyltyrosine (N-AcTyr) or glycyltyrosine (GlyTyr). Aromatic amino acid metabolism, growth, and nitrogen utilization were measured. Average amino acid and energy intakes were 14.6 g.kg-1.day-1 and 1,050 kJ.kg-1.day-1. Nitrogen balance and utilization were significantly higher (P < 0.05) in piglets in the control Phe group and on the GlyTyr regimen. The high urinary excretion of N-AcTyr (65%) confirms its low bioavailability. Flux and oxidation were significantly higher (P < 0.05) in the Phe group. High plasma Phe levels and excretion of Phe catabolites, as well as the high plasma tyrosine in the GlyTyr group, indicate that current strategies employed to meet the aromatic amino acid needs of neonates on TPN need further refinement.

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Xuebijing Injection Affects the Dynamic Change of Metabolism in CLP-Induced Septic Rats

10.21203/rs.3.rs-526582/v1 ◽

2021 ◽

Author(s):

Yanjuan Liu ◽

Qi Zeng ◽

Wen Xiao ◽

Fang Chen ◽

Lianhong Zou ◽

...

Keyword(s):

Amino Acid ◽

Metabolic Pathways ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Dynamic Change ◽

Sepsis Group ◽

Control Group ◽

Multivariate Statistical ◽

Xuebijing Injection ◽

Kegg Pathway Analysis

Abstract Xuebijing injection has been widely applied to treat sepsis. However, its roles in the dynamic change of metabolism in sepsis are still unknown. In our study, Gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical techniques was used to detect the metabolic change in septic rats with or without XBJ injection treatment. The KEGG pathway analysis was used to further analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change, variable important in projection, and P value, we found 11, 33 and 26 differential metabolites in the sepsis group at 2, 6 and 12 hours post CLP, compared with the control group. Besides, we also found 32, 23 and 28 differential metabolites in the XBJ group at 2, 6 and 12 hours post CLP. The related pathways of differential metabolites were glycometabolism at 2h, glycometabolism and amino acid metabolism at 6h and amino acid metabolism at 12h post CLP in the sepsis group compared with the control group. Besides, glycometabolism, amino acid metabolism and lipid metabolism changed markedly after XBJ injection for 2 hours; while only amino acid metabolism changed significantly with the treatment of XBJ injection for 6 and 12 hours, compared with the sepsis group. Further analysis showed 3, 6 and 6 differential metabolites were overlapped in the sepsis group and XBJ group at 2, 6 and 12 hours post CLP. These identified differential metabolites were majorly involved in arginine and proline metabolism, suggesting that XBJ injection is capable of improving metabolic disorders in CLP-induced septic rat to a certain extent.

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Lysine Restriction Affects Feed Intake and Amino Acid Metabolism via Gut Microbiome in Piglets

Cellular Physiology and Biochemistry ◽

10.1159/000485782 ◽

2017 ◽

Vol 44 (5) ◽

pp. 1749-1761 ◽

Cited By ~ 43

Author(s):

Jie Yin ◽

Hui Han ◽

Yuying Li ◽

Zhaojin Liu ◽

Yurong Zhao ◽

...

Keyword(s):

Amino Acid ◽

Feeding Behavior ◽

Microbial Communities ◽

Feed Intake ◽

Gut Microbiome ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Rrna Genes ◽

Control Group ◽

Restricted Group

Background/Aims: Our previous reports suggested that dietary supplementation with lysine influenced intestinal absorption and metabolism of amino acids. In this study, we further investigated the effect of lysine restriction (30%) on feed intake and we also tested the hypothesis that gut microbiome contributed to the potential mechanism of lysine restriction-mediated feeding behavior. Here, we profiled gut microbial communities by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from gut samples as well as growth performance, serum hormones, and intestinal lysine transport in a piglet model. Results: Piglets preferred to the lysine restricted diet when giving three diets and the feed intake was markedly higher in the lysine-restricted group than that in the control group. Altered hormones (leptin, CCK, and ghrelin) might contribute to the feeding behavior caused by lysine restriction. Meanwhile, lysine transporting ability (SLC7A1 and SLC7A2 expression, intestinal electrophysiological changes, and amino acid pool in mesenteric vein) was decreased in response to lysine restriction. Through deep sequencing of bacterial rRNA markers, we observed that bacterial diversity was enhanced in the lysine-restricted group (Shannon H, PD, and Chao1). At the phylum level, lysine restriction enhanced gut Actinobacteria, Saccharibacteria, and Synergistetes abundances. At the family level, Moraxellaceae, Halomonadaceae, Shewanellaceae, Corynebacteriaceae, Bacillaceae, Comamonadaceae, Microbacteriaceae, Caulobacteraceae, and Synergistaceae abundances were increased in response to lysine restriction. Predictive functional profiling of microbial communities by PICRUSt also confirmed that dietary lysine restriction affected gut microbiome, which might further mediate amino acid metabolism, membrane transport, and endocrine system. Conclusion: Our results indicated that lysine restriction inhibited intestinal lysine transport and promoted feed intake, which might be associated with gut microbiome.

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The Potential Relationship Between HIF-1α and Amino Acid Metabolism After Hypoxic Ischemia and Dual Effects on Neurons

Frontiers in Neuroscience ◽

10.3389/fnins.2021.676553 ◽

2021 ◽

Vol 15 ◽

Author(s):

Kexin Li ◽

Yang Zheng ◽

Xiaoming Wang

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Hippocampal Neurons ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Cerebral Metabolism ◽

Control Group ◽

Induction Effect ◽

Glutamate Cysteine Ligase ◽

Hypoxic Ischemia

Hypoxia inducible factor (HIF) is one of the major transcription factors through which cells and tissues adapt to hypoxic-ischemic injury. However, the specific mechanism by which HIF regulates amino acid metabolism and its effect on neurons during hypoxic ischemia (HI) have remained unclear. This study analyzed the changes in cerebral metabolism of amino acids after HI by using 1H-MRS and investigated the relationship between the changes in cerebral metabolism of amino acids and HIF-1α as well as the potential effects on neurons. Newborn pigs were used as an HI model in this study. Twenty-eight newborn Yorkshire pigs (male, 1.0–1.5 kg) aged 3–5 days were selected and randomly divided into experimental groups tested at 0–2 h (n = 4), 2–6 h (n = 4), 6–12 h (n = 4), 12–24 h (n = 4), 24–48 h (n = 4), and 48–72 h (n = 4) after HI, and a control group (n = 4). After the modeling was completed, 1H-MRS imaging was conducted, followed by immunohistochemical staining of HIF-1α, NeuN, and doublecortin (DCX), and immunofluorescence of glutamic oxaloacetic transaminase (GOT)-1, GOT2, glutathione synthase (GS), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) in brain tissues. The expression of HIF-1α exhibited two increases after HI injury. The first time was opposite to the trends of change of GOT2, aspartic acid, and the number of neurons, while the second was consistent with these trends, suggesting that HIF-1α may have a two-way induction effect on neurons by regulating GOT2 after HI. HIF-1α was closely related to GCLM expression, and GSH level was correlated with the number of hippocampal neurons, indicating that HIF-1α may regulate GCLM to promote GSH synthesis and additionally play a neuroprotective role.

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Blood sulfur-amino acid concentration reflects an impairment of liver transsulfuration pathway in patients with acute abdominal inflammatory processes

British Journal Of Nutrition ◽

10.1079/bjn2000237 ◽

2001 ◽

Vol 85 (2) ◽

pp. 173-178 ◽

Cited By ~ 4

Author(s):

Juan R. Viñ ◽

Angel Giménez ◽

Adelina Corbacho ◽

Inmaculada R. Puertes ◽

Elisa Borrás ◽

...

Keyword(s):

Amino Acid ◽

Free Amino ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Control Group ◽

Sulfur Amino Acid ◽

Homocysteine Concentration ◽

Transsulfuration Pathway ◽

Inflammatory Processes ◽

Work Supports

Whole-blood free amino acids were measured in a control group made up of eight healthy women fasted for 12 h and also in eight patients with acute pancreatitis, five patients with acute cholecystitis and seven patients with acute appendicitis. Blood was withdrawn immediately on admission to hospital and again 3 d later following a controlled peripheral parenteral nutrition diet; this is with the exception of the appendicitis group. L-CYSTATHIONINE AND l-methionine concentrations were significantly higher in pancreatitis and appendicitis patients when compared with controls. In the pancreatitis and cholecystitis patients, l-serine concentration was also significantly higher when compared with controls. The l-homocysteine concentration was significantly higher only in the appendicitis group when compared with the control group. l-Cystine concentration was unchanged in all the patients studied when compared with control subjects. The l-methionine : l-cystine ratio was significantly higher and the l-glutamine : l-cystine ratio was significantly lower in all the patients when compared with controls. The blood S-amino acid pattern reflects an impairment in liver transsulfuration pathway during acute abdominal processes. This work supports the idea that the l-methionine : l-cystine and l-glutamine : l-cystine ratios can be taken as good markers to evaluate the S-amino acid metabolism and suggests the importance of using N-acetylcysteine as a required nutrient in these situations.

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Effect of Heat Stress on Bovine Mammary Cellular Metabolites and Gene Transcription Related to Amino Acid Metabolism, Amino Acid Transportation and Mammalian Target of Rapamycin (mTOR) Signaling

Animals ◽

10.3390/ani11113153 ◽

2021 ◽

Vol 11 (11) ◽

pp. 3153

Author(s):

Lin Fu ◽

Li Zhang ◽

Li Liu ◽

Heng Yang ◽

Peng Zhou ◽

...

Keyword(s):

Amino Acid ◽

Mrna Expression ◽

Signaling Pathway ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Mammary Epithelial ◽

Mtor Signaling ◽

Control Group ◽

Mtor Signaling Pathway ◽

Lactation Performance

Heat stress (HS) is one of the most serious factors to negatively affect the lactation performance of dairy cows. Bovine mammary epithelial cells are important for lactation. It was demonstrated that HS decreases the lactation performance of dairy cows, partly through altering gene expression within bovine mammary epithelial tissue. However, the cellular metabolism mechanisms under HS remains largely unknown. The objective of this study was to determine whether HS induced changes in intracellular metabolites and gene transcription related to amino acid metabolism, amino acid transportation and the mTOR signaling pathway. Immortalized bovine mammary epithelial cell lines (MAC-T cells, n = 5 replicates/treatment) were incubated for 12 h at 37 °C (Control group) and 42 °C (HS group). Relative to the control group, HS led to a greater mRNA expression of heat shock protein genes HSF1, HSPB8, HSPA5, HSP90AB1 and HSPA1A. Compared with the control group, metabolomics using liquid chromatography tandem–mass spectrometry identified 417 differential metabolites with p < 0.05 and a variable importance in projection (VIP) score >1.0 in the HS group. HS resulted in significant changes to the intracellular amino acid metabolism of glutathione, phenylalanine, tyrosine, tryptophan, valine, leucine, isoleucine, arginine, proline, cysteine, methionine, alanine, aspartate and glutamate. HS led to a greater mRNA expression of the amino acid transporter genes SLC43A1, SLC38A9, SLC36A1, and SLC3A2 but a lower mRNA expression of SLC7A5 and SLC38A2. Additionally, HS influenced the expression of genes associated with the mTOR signaling pathway and significantly upregulated the mRNA expression of mTOR, AKT, RHEB, eIF4E and eEF2K but decreased the mRNA expression of TSC1, TSC2 and eEF2 relative to the control group. Compared with the control group, HS also led to greater mRNA expression of the CSN1S2 gene. Overall, our study indicates that bovine mammary epithelial cells may have the ability to resist HS damage and continue milk protein synthesis partly through enhanced intracellular amino acid absorption and metabolism and by activating the mTOR signaling pathway during HS.

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Metabolic changes in mouse plasma after acute diquat poisoning by UPLC-MS/MS

Current Pharmaceutical Analysis ◽

10.2174/1573412916999200624160304 ◽

2020 ◽

Vol 16 ◽

Author(s):

Lianguo Chen ◽

Zuoquan Zhong ◽

Jiawen Liu ◽

Congcong Wen ◽

Yongxi Jin ◽

...

Keyword(s):

Lactic Acid ◽

Amino Acid ◽

Citric Acid ◽

Energy Metabolism ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Lethal Dose ◽

Control Group ◽

Mouse Plasma ◽

Fast Acting

Introduction: Diquat is a fast-acting contact herbicide and plant dehydrating agent. The oral lethal dose 50 (LD50) of diquat in mice is about 125 mg/kg. The purpose of this study is to research the metabolomics in mouse plasma after acute diquat poisoning. Method: These mice were divided into two groups (the control group and acute diquat poisoning group). The control group was given normal saline by gavage. The acute diquat poisoning group was given 50 mg/kg diquat. UPLC-MS/MS was used to determinate the small molecule organic acid in mouse plasma. Results: Compare to the control group, the L-lysine, Adenine, L-Alanine, L-Valine, Lactic acid, Inosine, Adenosine, LTryptophan, L-Tyrosine, L-Arginine, L-Phenylalanine, L-Methionine, Citric acid, Fructose, L-Glutamine, Malic acid, LAspartic acid and Pyruvic acid increased in the acute diquat poisoning group (p<0.05); while the L-Histidine decreased (p<0.05). Conclusion: The results of metabolites increased or decreased, indicating that acute diquat poisoning induced amino acid metabolism and energy metabolism perturbations in mice.

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The biochemical and metabolic profiles of dairy cows with mycotoxins-contaminated diets

PeerJ ◽

10.7717/peerj.8742 ◽

2020 ◽

Vol 8 ◽

pp. e8742

Author(s):

Qian Wang ◽

Yangdong Zhang ◽

Nan Zheng ◽

Shengguo Zhao ◽

Songli Li ◽

...

Keyword(s):

Amino Acid ◽

Dairy Cows ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Plasma Metabolites ◽

Control Group ◽

Treatment Groups ◽

Total Antioxidant ◽

Biochemical Profiles ◽

Biochemical Analyses

Background Previous studies on the effects of mycotoxins have solely focused on their biochemical profiles or products in dairy ruminants. Changes in metabolism that occur after exposure to mycotoxins, as well as biochemical changes, have not been explored. Methods We measured the biochemical and metabolic changes in dairy cows after exposure to mycotoxins using biochemical analyses and nuclear magnetic resonance. Twenty-four dairy cows were randomly assigned to three different treatment groups. Control cows received diets with 2 kg uncontaminated cottonseed. Cows in the 50% replacement group received the same diet as the control group, but with 1 kg of uncontaminated cottonseed and 1 kg of cottonseed contaminated with mycotoxins. Cows in the 100% replacement group received the same diet as the control, but with 2 kg contaminated cottonseed. Results The results showed that serum γ-glutamyl transpeptidase and total antioxidant capacities were significantly affected by cottonseed contaminated with mycotoxins. There were also significant differences in isovalerate and NH3-N levels, and significant differences in the eight plasma metabolites among the three groups. These metabolites are mainly involved in amino acid metabolism pathways. Therefore, the results suggest that amino acid metabolism pathways may be affected by mycotoxins exposure.

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