scholarly journals Metabolism Plays a Key Role during Macrophage Activation

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Marion I. Stunault ◽  
Gaël Bories ◽  
Rodolphe R. Guinamard ◽  
Stoyan Ivanov
Keyword(s):  
Fatty Acid ◽  
Immune Cells ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Macrophage Activation ◽  
Acid Metabolism ◽  
Tissue Homeostasis ◽  
Surface Markers ◽  
Cell Surface Markers ◽  
External Stimuli

Monocyte and macrophage diversity is evidenced by the modulation of cell surface markers and differential production of soluble mediators. These immune cells play key roles in controlling tissue homeostasis, infections, and excessive inflammation. Macrophages remove dead cells in a process named efferocytosis, contributing to the healthy tissue maintenance. Recently, it became clear that the main macrophage functions are under metabolic control. Modulation of glucose, fatty acid, and amino acid metabolism is associated with various macrophage activations in response to external stimuli. Deciphering these metabolic pathways provided critical information about macrophage functions.

scholarly journals Using Transcriptome Analysis to Screen for Key Genes and Pathways Related to Cytoplasmic Male Sterility in Cotton (Gossypium hirsutum L.)

2019 ◽  
Vol 20 (20) ◽  
pp. 5120 ◽  
Author(s):  
Yuqing Li ◽  
Tengfei Qin ◽  
Chunyan Wei ◽  
Jialiang Sun ◽  
Tao Dong ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Energy Metabolism ◽  
Male Sterility ◽  
Carbohydrate Metabolism ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Anther Development ◽  
Gossypium Hirsutum L ◽  
Key Genes

Cotton (Gossypium hirsutum L.) is one of the most important cash crops worldwide. Cytoplasmic male sterility (CMS) is an excellent breeding system for exploitation of heterosis, which has great potential to increase crop yields. To understand the molecular mechanism of CMS in cotton, we compared transcriptome, cytomorphological, physiological and bioinformatics data between the CMS line C2P5A and its maintainer line C2P5B. By using high-throughput sequencing technology, 178,166 transcripts were assembled and 2013 differentially expression genes (DEGs) were identified at three different stages of C2P5A anther development. In this study, we identified DEGs associated with reactive oxygen species (ROS), peroxisomes, aldehyde dehydrogenases (ALDH), cytochrome oxidase subunit VI, and cytochrome P450, and DEGs associated with tapetum development, Jojoba acyl-CoA reductase-related male sterility protein, basic helix-loop-helix (bHLH) and MYB transcription factors. The abnormal expression of one of these genes may be responsible for the CMS C2P5A line. In gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, DEGs were mainly related to carbohydrate metabolism, amino acid metabolism, transport and catabolism, and signal transduction. Carbohydrate metabolism provides energy for anther development, starch and sucrose metabolism, fatty acid biosynthesis and metabolism and ascorbate and aldarate metabolism. These results showed that numerous genes and multiple complex metabolic pathways regulate cotton anther development. Weighted correlation network analysis (WGCNA) indicated that three modules, ‘turquoise,’ ‘blue,’ and ‘green,’ were specific for the CMS C2P5A line. The ‘turquoise’ and ‘blue’ modules were mainly related to carbohydrate metabolism, amino acid metabolism, energy metabolism, peroxisomes, pyruvate metabolism as well as fatty acid degradation. The ‘green’ module was mainly related to energy metabolism, carbon metabolism, translation, and lipid metabolism. RNA-sequencing and WGCNA polymerization modules were screened for key genes and pathways related to CMS in cotton. This study presents a new perspective for further research into the metabolic pathways of pollen abortion in the CMS C2P5A line and also provides a theoretical basis for its breeding and production.

scholarly journals Comprehensive transcriptome and metabolome profiling reveal metabolic mechanisms of Nitraria sibirica Pall. to salt stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huanyong Li ◽  
Xiaoqian Tang ◽  
Xiuyan Yang ◽  
Huaxin Zhang
Keyword(s):  
Salt Stress ◽  
Amino Acid ◽  
Salt Tolerance ◽  
Metabolic Pathways ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Sulfur Metabolism ◽  
Enrichment Analysis ◽  
Extracellular Region ◽  
Nitraria Sibirica

AbstractNitraria sibirica Pall., a typical halophyte that can survive under extreme drought conditions and in saline-alkali environments, exhibits strong salt tolerance and environmental adaptability. Understanding the mechanism of molecular and physiological metabolic response to salt stress of plant will better promote the cultivation and use of halophytes. To explore the mechanism of molecular and physiological metabolic of N. sibirica response to salt stress, two-month-old seedlings were treated with 0, 100, and 400 mM NaCl. The results showed that the differentially expressed genes between 100 and 400 mmol L−1 NaCl and unsalted treatment showed significant enrichment in GO terms such as binding, cell wall, extemal encapsulating structure, extracellular region and nucleotide binding. KEGG enrichment analysis found that NaCl treatment had a significant effect on the metabolic pathways in N. sibirica leaves, which mainly including plant-pathogen interaction, amino acid metabolism of the beta alanine, arginine, proline and glycine metabolism, carbon metabolism of glycolysis, gluconeogenesis, galactose, starch and sucrose metabolism, plant hormone signal transduction and spliceosome. Metabolomics analysis found that the differential metabolites between the unsalted treatment and the NaCl treatment are mainly amino acids (proline, aspartic acid, methionine, etc.), organic acids (oxaloacetic acid, fumaric acid, nicotinic acid, etc.) and polyhydric alcohols (inositol, ribitol, etc.), etc. KEGG annotation and enrichment analysis showed that 100 mmol L−1 NaCl treatment had a greater effect on the sulfur metabolism, cysteine and methionine metabolism in N. sibirica leaves, while various amino acid metabolism, TCA cycle, photosynthetic carbon fixation and sulfur metabolism and other metabolic pathways have been significantly affected by 400 mmol L−1 NaCl treatment. Correlation analysis of differential genes in transcriptome and differential metabolites in metabolome have found that the genes of AMY2, BAM1, GPAT3, ASP1, CML38 and RPL4 and the metabolites of L-cysteine, proline, 4-aminobutyric acid and oxaloacetate played an important role in N. sibirica salt tolerance control. This is a further improvement of the salt tolerance mechanism of N. sibirica, and it will provide a theoretical basis and technical support for treatment of saline-alkali soil and the cultivation of halophytes.

scholarly journals Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut

2018 ◽  
Vol 115 (45) ◽  
pp. E10712-E10719 ◽  
Author(s):  
Reed Pifer ◽  
Regan M. Russell ◽  
Aman Kumar ◽  
Meredith M. Curtis ◽  
Vanessa Sperandio
Keyword(s):  
Fatty Acid ◽  
High Throughput ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Virulence Genes ◽  
Acid Metabolism ◽  
Feedback Mechanism ◽  
Regulatory Pathways ◽  
Successful Infection ◽  
Cellular Circuits

The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagicEscherichia coli(EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.

scholarly journals The Diverse Functions of Non-Essential Amino Acids in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 675 ◽  
Author(s):  
Bo-Hyun Choi ◽  
Jonathan L. Coloff
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cancer Therapy ◽  
Metabolic Pathways ◽  
Essential Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Essential Amino Acids ◽  
Redox Status ◽  
Antioxidant Systems

Far beyond simply being 11 of the 20 amino acids needed for protein synthesis, non-essential amino acids play numerous important roles in tumor metabolism. These diverse functions include providing precursors for the biosynthesis of macromolecules, controlling redox status and antioxidant systems, and serving as substrates for post-translational and epigenetic modifications. This functional diversity has sparked great interest in targeting non-essential amino acid metabolism for cancer therapy and has motivated the development of several therapies that are either already used in the clinic or are currently in clinical trials. In this review, we will discuss the important roles that each of the 11 non-essential amino acids play in cancer, how their metabolic pathways are linked, and how researchers are working to overcome the unique challenges of targeting non-essential amino acid metabolism for cancer therapy.

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

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.

scholarly journals Lactobacillus frumenti mediates energy production via fatty acid β-oxidation in the liver of early-weaned piglets

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhichang Wang ◽  
Jun Hu ◽  
Wenyong Zheng ◽  
Tao Yang ◽  
Xinkai Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Gut Microbiota ◽  
Oral Administration ◽  
Energy Production ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Critical Role ◽  
Guanosine Monophosphate ◽  
Weaned Piglets

Abstract Background Early-weaning of piglets is often accompanied by severe disorders, especially diarrhea. The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeostasis of the host. Our previous studies have demonstrated that oral administration of Lactobacillus frumenti improves epithelial barrier functions and confers diarrhea resistance in early-weaned piglets. However, the metabolic response to L. frumenti administration remains unclear. Then, we conducted simultaneous serum and hepatic metabolomic analyses in early-weaned piglets administered by L. frumenti or phosphate-buffered saline (PBS). Results A total of 100 6-day-old crossbred piglets (Landrace × Yorkshire) were randomly divided into two groups and piglets received PBS (sterile, 2 mL) or L. frumenti (suspension in PBS, 108 CFU/mL, 2 mL) by oral administration once per day from 6 to 20 days of age. Piglets were weaned at 21 days of age. Serum and liver samples for metabolomic analyses were collected at 26 days of age. Principal components analysis (PCA) showed that L. frumenti altered metabolism in serum and liver. Numerous correlations (P < 0.05) were identified among the serum and liver metabolites that were affected by L. frumenti. Concentrations of guanosine monophosphate (GMP), inosine monophosphate (IMP), and uric acid were higher in serum of L. frumenti administration piglets. Pathway analysis indicated that L. frumenti regulated fatty acid and amino acid metabolism in serum and liver. Concentrations of fatty acid β-oxidation related metabolites in serum (such as 3-hydroxybutyrylcarnitine, C4-OH) and liver (such as acetylcarnitine) were increased after L. frumenti administration. Conclusions Our findings suggest that L. frumenti regulates lipid metabolism and amino acid metabolism in the liver of early-weaned piglets, where it promotes fatty acid β-oxidation and energy production. High serum concentrations of nucleotide intermediates, which may be an alternative strategy to reduce the incidence of diarrhea in early-weaned piglets, were further detected. These findings broaden our understanding of the relationships between the gut microbiota and nutrient metabolism in the early-weaned piglets.

scholarly journals Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects

2013 ◽  
Vol 22 (25) ◽  
pp. 5249-5261 ◽  
Author(s):  
Sander M. Houten ◽  
Hilde Herrema ◽  
Heleen te Brinke ◽  
Simone Denis ◽  
Jos P.N. Ruiter ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Amino Acid ◽  
Fatty Acid Oxidation ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Acid Oxidation

scholarly journals Cathepsin Inhibition Modulates Metabolism and Polarization of Tumor-Associated Macrophages

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2579
Author(s):  
Diana Oelschlaegel ◽  
Tommy Weiss Sadan ◽  
Seth Salpeter ◽  
Sebastian Krug ◽  
Galia Blum ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Immune Cells ◽  
Fatty Acid Synthase ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Marker Genes ◽  
Tumor Associated Macrophages ◽  
Cathepsin Activity ◽  
The Impact

Stroma-infiltrating immune cells, such as tumor-associated macrophages (TAM), play an important role in regulating tumor progression and chemoresistance. These effects are mostly conveyed by secreted mediators, among them several cathepsin proteases. In addition, increasing evidence suggests that stroma-infiltrating immune cells are able to induce profound metabolic changes within the tumor microenvironment. In this study, we aimed to characterize the impact of cathepsins in maintaining the TAM phenotype in more detail. For this purpose, we investigated the molecular effects of pharmacological cathepsin inhibition on the viability and polarization of human primary macrophages as well as its metabolic consequences. Pharmacological inhibition of cathepsins B, L, and S using a novel inhibitor, GB111-NH2, led to changes in cellular recycling processes characterized by an increased expression of autophagy- and lysosome-associated marker genes and reduced adenosine triphosphate (ATP) content. Decreased cathepsin activity in primary macrophages further led to distinct changes in fatty acid metabolites associated with increased expression of key modulators of fatty acid metabolism, such as fatty acid synthase (FASN) and acid ceramidase (ASAH1). The altered fatty acid profile was associated with an increased synthesis of the pro-inflammatory prostaglandin PGE2, which correlated with the upregulation of numerous NFkB-dependent pro-inflammatory mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and tumor necrosis factor-alpha (TNFα). Our data indicate a novel link between cathepsin activity and metabolic reprogramming in macrophages, demonstrated by a profound impact on autophagy and fatty acid metabolism, which facilitates a pro-inflammatory micromilieu generally associated with enhanced tumor elimination. These results provide a strong rationale for therapeutic cathepsin inhibition to overcome the tumor-promoting effects of the immune-evasive tumor micromilieu.

scholarly journals Metabolomics Deciphered Metabolic Reprogramming Required for Biofilm Formation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Haitao Lu ◽  
Yumei Que ◽  
Xia Wu ◽  
Tianbing Guan ◽  
Hao Guo
Keyword(s):  
High Frequency ◽  
Metabolic Pathways ◽  
Biofilm Formation ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Antibiotics Resistance ◽  
Targeted Metabolomics ◽  
Metabolic Phenotyping ◽  
Insight Into

Abstract Biofilm formation plays a key role in many bacteria causing infections, which mostly accounts for high-frequency infectious recurrence and antibiotics resistance. In this study, we sought to compare modified metabolism of biofilm and planktonic populations with UTI89, a predominant agent of urinary tract infection, by combining mass spectrometry based untargeted and targeted metabolomics methods, as well as cytological visualization, which enable us to identify the driven metabolites and associated metabolic pathways underlying biofilm formation. Surprisingly, our finding revealed distinct differences in both phenotypic morphology and metabolism between two patterns. Furthermore, we identified and characterized 38 differential metabolites and associated three metabolic pathways involving glycerolipid metabolism, amino acid metabolism and carbohydrate metabolism that were altered mostly during biofilm formation. This discovery in metabolic phenotyping permitted biofilm formation shall provide us a novel insight into the dissociation of biofilm, which enable to develop novel biofilm based treatments against pathogen causing infections, with lower antibiotic resistance.

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