Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

Wang, Hao; Zheng, Xueyue; Liu, Bingnan; Xia, Yaoyao; Xin, Zhongquan; Deng, Baichuan; He, Liuqin; Deng, Jinping; Ren, Wenkai

doi:10.3389/fimmu.2021.753092

Cited by 27 publications

(19 citation statements)

References 62 publications

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“…While high content of aspartic acid can be a toxin, which induces hyperexcitability of neurons, eliciting degeneration of neurons with excess, which will ultimately develop to cognitive impairment ( 22 ). Another, current research has suggested the accelerative role of aspartate metabolism in the inflammatory responses ( 23 ). Related studies generally have pointed out that the pathogenesis of cognitive impairment in SCZ is closely related to the abnormal immune system ( 24 ).…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomics of schizophrenia with cognitive impairment: A pilot study

Jiang

Sun²,

Hu³

et al. 2022

Front. Psychiatry

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Schizophrenia (SCZ) acts as a complex and burdensome disease, in which the functional outcome can be validly predicted by cognitive impairment, as one of the core features. However, there still lack considerable markers of cognitive deficits in SCZ. Based on metabolomics, it is expected to identify different metabolic characteristics of SCZ with cognitive impairment. In the present study, 17 SCZ patients with cognitive impairment (CI), 17 matched SCZ patients with cognitive normal (CN), and 20 healthy control subjects (HC) were recruited, whose plasma metabolites were measured using ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC–MS/MS). The result of metabolic profiling indicated the identification of 46 differentially expressed metabolites between HC, CN, and CI groups, with 7 differentially expressed metabolites between CN and CI groups. Four differential metabolites (imidazolepropionic acid, Homoserine, and Aspartic acid) were repeatedly found in both screenings, by which the formed biomarker panel could discriminate SCZ with cognitive impairment from matched patients (AUC = 0.974) and health control (AUC = 0.841), respectively. Several significant metabolic pathways were highlighted in pathway analysis, involving Alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, and Citrate cycle (TCA cycle). In this study, several differentially expressed metabolites were identified in SCZ with cognitive impairment, providing novel insights into clinical treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Plasma metabolomics of schizophrenia with cognitive impairment: A pilot study

Jiang

Sun²,

Hu³

et al. 2022

Front. Psychiatry

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“…In particular, the finding that glutamine supplies both carbon and reduced nitrogen for the formation of aspartate suggests a potentially important role of aspartate in M1-like macrophages. Indeed, aspartate has been shown to promote IL-1β secretion in M1 macrophages by boosting the activation of HIF-1α ( 59 ). In regard to other amino acids, we detected only weak labeling of U 15 N glutamine into valine and isoleucine ( Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

Glutamine Is Required for M1-like Polarization of Macrophages in Response to Mycobacterium tuberculosis Infection

Jiang

Qiu

Kurland

et al. 2022

mBio

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Macrophages play essential roles in determining the progression and final outcome of human infection by Mycobacterium tuberculosis . While upregulation of hypoxia-inducible-factor 1 (HIF-1) and a metabolic reprogramming to the Warburg Effect-like state are known to be critical for immune cell activation in response to M. tuberculosis infection, our overall knowledge about the immunometabolism of M1-like macrophages is poor.

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“…Asparagine is a metabolite from aspartate metabolism. Large amounts of evidence indicate that aspartate could promote a macrophage-mediated inflammatory response and attenuate intestinal damage caused by endotoxins in weaned pigs [ 77 , 78 ]. No differences were observed in serum and ileal mucosa metabolites in pigs fed with different doses of botanical blend 2, which is consistent with intestinal microbiota data and indicates no dose response was observed in botanical blend 2 regarding intestinal microbiota and metabolomics.…”

Section: Discussionmentioning

confidence: 99%

Dietary Supplementation with Botanical Blends Modified Intestinal Microbiota and Metabolomics of Weaned Pigs Experimentally Infected with Enterotoxigenic Escherichia coli

Jinno

Wong

Wall³

et al. 2023

Microorganisms

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The objective of this study was to investigate supplementation of botanical blends (BB) comprised of 0.3% capsicum oleoresin and 12% garlic oil on gut microbiota and metabolomic profiles in serum and ileal mucosa of Escherichia coli infected pigs. Sixty weaned pigs were assigned to one of five treatments: negative control (CON−), positive control (CON+), dietary supplementation of 100 ppm BB1, 50 or 100 ppm BB2. All pigs, except CON−, were orally inoculated with 1010 CFU F18 ETEC/3-mL dose for 3 consecutive days after 7 d adaption. Feces, ileal digesta and cecal content were collected for 16S rRNA amplicon sequencing. Serum and ileal mucosa underwent primary metabolomics analysis. Supplementing 100 ppm BB1 increased (P < 0.05) relative abundances of Enterobacteriaceae and Escherichia–Shigella in ileum, and the relative abundances of Bacteroidota and Prevotellaceae in cecum than CON+ on d 5 post-inoculation (PI). Supplementing 100 ppm BB2 upregulated serum pinitol on d 4 PI and serum cholesterol and aminomalonic acids on d 21 PI, while supplementing 50 ppm BB2 reduced asparagine in ileal mucosa on d 5 PI than CON+. Supplementation with botanical blends modulated ileal and cecal microbiota and serum metabolomics profiles in weaned pigs under Escherichia coli challenge.

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Aspartate Metabolism Facilitates IL-1β Production in Inflammatory Macrophages

Cited by 27 publications

References 62 publications

Plasma metabolomics of schizophrenia with cognitive impairment: A pilot study

Plasma metabolomics of schizophrenia with cognitive impairment: A pilot study

Glutamine Is Required for M1-like Polarization of Macrophages in Response to Mycobacterium tuberculosis Infection

Dietary Supplementation with Botanical Blends Modified Intestinal Microbiota and Metabolomics of Weaned Pigs Experimentally Infected with Enterotoxigenic Escherichia coli

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