Chronic PM exposure disrupts intestinal barrier integrity via microbial dysbiosis-triggered TLR2/5-MyD88-NLRP3 inflammasome activation.

Background: PM, a known public health risk, is increasingly linked to intestinal disorders, however, the mechanisms of its impact are not fully understood.

Purpose: This study aimed to explore the impact of chronic PM exposure on intestinal barrier integrity and to uncover the underlying molecular mechanisms.

Methods: C57BL/6 J mice were exposed to either concentrated ambient PM (CPM) or filtered air (FA) for six months to simulate urban pollution conditions.

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline: A Community-Based Cohort Study.

Unlabelled: Cardiovascular health metrics are now widely recognized as modifiable risk factors for cognitive decline and dementia. Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia. Circulating metabolites profiling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline.

Ketogenic diet-produced β-hydroxybutyric acid accumulates brain GABA and increases GABA/glutamate ratio to inhibit epilepsy.

Ketogenic diet (KD) alleviates refractory epilepsy and reduces seizures in children. However, the metabolic/cell biologic mechanisms by which the KD exerts its antiepileptic efficacy remain elusive. Herein, we report that KD-produced β-hydroxybutyric acid (BHB) augments brain gamma-aminobutyric acid (GABA) and the GABA/glutamate ratio to inhibit epilepsy.

Profiles and integration of the gut microbiome and fecal metabolites in severe intrahepatic cholestasis of pregnancy.

Background: The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) remains unknown. The gut microbiome and its metabolites play important roles in bile acid metabolism, and previous studies have indicated the association of the gut microbiome with ICP.

Methods: We recruited a cohort of 5100 participants, and 20 participants were enrolled in the severe ICP group, matched with 20 participants in the mild ICP group and 20 controls.

Phenylalanine impairs insulin signaling and inhibits glucose uptake through modification of IRβ.

Whether amino acids act on cellular insulin signaling remains unclear, given that increased circulating amino acid levels are associated with the onset of type 2 diabetes (T2D). Here, we report that phenylalanine modifies insulin receptor beta (IRβ) and inactivates insulin signaling and glucose uptake. Mice fed phenylalanine-rich chow or phenylalanine-producing aspartame or overexpressing human phenylalanyl-tRNA synthetase (hFARS) develop insulin resistance and T2D symptoms.

Erratum: Cardiomyocyte-Restricted Low Density Lipoprotein Receptor-Related Protein 6 (LRP6) Deletion Leads to Lethal Dilated Cardiomyopathy Partly Through Drp1 Signaling: Erratum.

[This corrects the article DOI: 10.7150/thno.22177.

Anopheline mosquitoes are protected against parasite infection by tryptophan catabolism in gut microbiota.

The mosquito microbiota can influence host physiology and vector competence, but a detailed understanding of these processes is lacking. Here we found that the gut microbiota of Anopheles stephensi, a competent malaria vector, is involved in tryptophan metabolism and is responsible for the catabolism of the peritrophic matrix impairing tryptophan metabolites. Antibiotic elimination of the microbiota led to the accumulation of tryptophan and its metabolites-kynurenine, 3-hydroxykynurenine (3-HK) and xanthurenic acid.

Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake.

Protein fatty acylation regulates numerous cell signaling pathways. Polyunsaturated fatty acids (PUFAs) exert a plethora of physiological effects, including cell signaling regulation, with underlying mechanisms to be fully understood. Herein, we report that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) regulate PI3K-AKT signaling by modifying PDK1 and AKT2.

Nuclear dihydroxyacetone phosphate signals nutrient sufficiency and cell cycle phase to global histone acetylation.

Global histone acetylation varies with changes in the nutrient and cell cycle phases; however, the mechanisms connecting these variations are not fully understood. Herein, we report that nutrient-related and cell-cycle-regulated nuclear acetate regulates global histone acetylation. Histone deacetylation-generated acetate accumulates in the nucleus and induces histone hyperacetylation.

Differential Metabolites in Chinese Autistic Children: A Multi-Center Study Based on Urinary H-NMR Metabolomics Analysis.

Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-center study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms.

Glucose-mediated proliferation of a gut commensal bacterium promotes Plasmodium infection by increasing mosquito midgut pH.

Plant-nectar-derived sugar is the major energy source for mosquitoes, but its influence on vector competence for malaria parasites remains unclear. Here, we show that Plasmodium berghei infection of Anopheles stephensi results in global metabolome changes, with the most significant impact on glucose metabolism. Feeding on glucose or trehalose (the main hemolymph sugars) renders the mosquito more susceptible to Plasmodium infection by alkalizing the mosquito midgut.

Subchronic exposure to concentrated ambient PM2.5 perturbs gut and lung microbiota as well as metabolic profiles in mice.

Exposure to ambient fine particular matter (PM2.5) are linked to an increased risk of metabolic disorders, leading to enhanced rate of many diseases, such as inflammatory bowel disease (IBD), cardiovascular diseases, and pulmonary diseases; nevertheless, the underlying mechanisms remain poorly understood. In this study, BALB/c mice were exposed to filtered air (FA) or concentrated ambient PM2.

Associations between serum metabolites and subclinical atherosclerosis in a Chinese population: the Taizhou Imaging Study.

Metabolomics provides a promising tool for understanding the pathophysiology and identifying biomarkers of atherosclerosis. We aimed to estimate the associations between circulating metabolites and subclinical atherosclerosis in a Chinese cohort. The baseline serum levels of 38 metabolites of 489 individuals were measured using nuclear magnetic resonance.

Quantitative Metabonomic Phenotypes in Different Structures of Mung Bean () Seeds and Their Germination-Associated Dynamic Changes.

Plant seed germination involving dynamic water uptakes and biochemical changes is essential for preservation of plant germplasm resource and worldwide food supply. To understand the germination-associated compartmental biochemistry changes, we quantitatively analyzed the metabolite composition (metabonome) for embryonic axes, cotyledons, and testae of mung bean () seeds in three germination phases using the NMR-based metabonomics approach. We found that three structures of mung bean seeds had distinct metabonomic phenotypes dominated by 53 metabolites including amino acids, carbohydrates, organic acids, choline metabolites, nucleotides/nucleosides, and shikimate-mediated secondary metabolites together with calcium and magnesium cations.

Metabolomics and incident dementia in older Chinese adults: The Shanghai Aging Study.

Introduction: Metabolomics provide a promising tool to understand the pathogenesis and to identify novel biomarkers of dementia. This study aimed to determine circulating metabolites associated with incident dementia in a Chinese cohort, and whether a selected metabolite panel could predict dementia.

Methods: Thirty-eight metabolites in baseline serum were profiled by nuclear magnetic resonance in 1440 dementia-free participants followed 5 years in the Shanghai Aging Study.

Potential Crosstalk between Liver and Extra-liver Organs in Mouse Models of Acute Liver Injury.

Carbon tetrachloride (CCl4), Concanavalin A (ConA), bile duct ligation (BDL), and liver resection (LR) are four types of commonly used mouse models of acute liver injury. However, these four models belong to different types of liver cell damage while their application situations are often confounded. In addition, the systematic changes of multiple extra-liver organs after acute liver injury and the crosstalk between liver and extra-liver organs remain unclear.

Cardiac-specific LRP6 knockout induces lipid accumulation through Drp1/CPT1b pathway in adult mice.

We recently reported low-density lipoprotein receptor-related protein 6 (LRP6) decreased in dilated cardiomyopathy hearts, and cardiac-specific knockout mice displayed lethal heart failure through activation of dynamin-related protein 1 (Drp1). We also observed lipid accumulation in LRP6 deficiency hearts, but the detailed molecular mechanisms are unclear. Here, we detected fatty acids components in LRP6 deficiency hearts and explored the potential molecular mechanisms.

Metabolomics in the Development and Progression of Dementia: A Systematic Review.

Dementia has become a major global public health challenge with a heavy economic burden. It is urgently necessary to understand dementia pathogenesis and to identify biomarkers predicting risk of dementia in the preclinical stage for prevention, monitoring, and treatment. Metabolomics provides a novel approach for the identification of biomarkers of dementia.

Alterations of Bile Acids and Gut Microbiota in Obesity Induced by High Fat Diet in Rat Model.

Obesity has become a worldwide health issue and has attracted much public attention. In the current study, we aim to elucidate the roles of bile acids and their associations with gut microbiota during obesity development, employing high fat diet (HFD)-induced obesity in a rat model. We collected feces and plasma, liver tissues, and segments of intestinal tissues and a developed bile acids quantification method by employing an ultraperformance liquid chromatography coupled with mass spectrometry detection (UPLC-MS) strategy.

Cardiomyocyte-Restricted Low Density Lipoprotein Receptor-Related Protein 6 (LRP6) Deletion Leads to Lethal Dilated Cardiomyopathy Partly Through Drp1 Signaling.

Low density lipoprotein receptor-related protein 6 LRP6), a wnt co-receptor, regulates multiple functions in various organs. However, the roles of LRP6 in the adult heart are not well understood. We observed LRP6 expression in heart with end-stage dilated cardiomyopathy (DCM) by western blot.

Sensing and Transmitting Intracellular Amino Acid Signals through Reversible Lysine Aminoacylations.

Amino acids are known regulators of cellular signaling and physiology, but how they are sensed intracellularly is not fully understood. Herein, we report that each aminoacyl-tRNA synthetase (ARS) senses its cognate amino acid sufficiency through catalyzing the formation of lysine aminoacylation (K-AA) on its specific substrate proteins. At physiologic levels, amino acids promote ARSs bound to their substrates and form K-AAs on the ɛ-amine of lysines in their substrates by producing reactive aminoacyl adenylates.

Correlations of Fecal Metabonomic and Microbiomic Changes Induced by High-fat Diet in the Pre-Obesity State.

Obesity resulting from interactions of genetic and environmental factors becomes a serious public health problem worldwide with alterations of the metabolic phenotypes in multiple biological matrices involving multiple metabolic pathways. To understand the contributions of gut microbiota to obesity development, we analyzed dynamic alterations in fecal metabonomic phenotype using NMR and fecal microorganism composition in rats using pyrosequencing technology during the high-fat diet (HFD) feeding for 81 days (pre-obesity state). Integrated analysis of these two phenotypic datasets was further conducted to establish correlations between the altered rat fecal metabonome and gut microbiome.