Metabolomics articles within Nature Communications

Commensal microbes contribute considerably to mammalian metabolism. Here the authors report the relative contributions of microbiome, age and sex to metabolism throughout the body and uncover age- and sex- specificity in how microbes affect metabolite levels in mice.

Brown adipose tissue (BAT) is a specialized thermogenic organ that undergoes high demands of protein synthesis during thermogenic adaptation. Here, the authors show that the cold responsive phosphatase Ssu72 is required for mRNA translation that affects thermogenic adaptation in BAT.

Myocardial substrate metabolism in cardiac hypertrophy or heart failure shifts from fatty acid oxidation to a greater reliance on glycolysis. Here, the authors show that KLF7 can simultaneously regulate key enzymes in glycolysis and fatty acid oxidation to mitigate metabolic imbalance during cardiac hypertrophy.

Plant biosynthetic enzymes rapidly evolve to catalyze specialized reactions. Here, the authors present the crystal structure and mechanism of COSY, the enzyme involved in coumarin biosynthesis of the BAHD-acyltransferase family that catalyzes an intramolecular acyl transfer reaction through a proton exchange mechanism.

Flavin containing monooxygenase 2 (FMO-2) is known to increase lifespan under dietary restriction through incompletely understood mechanisms. Here the authors report that FMO-2 modifies tryptophan and methionine metabolic pathways to enhance stress resistance and slow aging in C. elegans.

Here, analyzing paired fecal and blood metabolomics and metagenomics data in a large cohort, Deng et al. uncover disparate associations of the gut microbiota with cardiometabolic diseases when utilizing either fecal or blood metabolome data, suggesting that sampling criteria may be a relevant factor in metabolomics-based association studies.

Here, using a mouse model, the authors report a previously undescribed role for medium-chain acyl-CoA dehydrogenase in host metabolism of gut microbiota metabolites, and show that circulating compounds, including the abundant organic acid hippurate, depend on host-microbe co-metabolism of phenylalanine by Clostridium sporogenes.

Volatile compounds to be released from the plant cell to the atmosphere must cross the cell wall. Here the authors show that cell-wall localized non-specific lipid transfer proteins facilitate the diffusion of volatiles across the hydrophilic cell wall.

Comparing experimental mass spectra to reference spectra can enable natural product identification, but these spectral libraries are often incomplete and not universally applicable. Here, the authors present SNAP-MS, a tool that allows assigning compound families without experimental or calculated reference spectra.

Biological sex affects all aspects of animal physiology. Using the model C. elegans, the authors show that metabolomes are highly sex-specific and include a vast space of yet unidentified metabolites that may control development and lifespan.

Primary and metastatic tumours have different metabolic phenotypes due to changes in nutrient availability. Here the authors perform multi-omic analyses of primary and metastatic renal cancer cells grown in a physiological medium and show that the reprogramming of the branched-chain amino acid catabolism and urea cycle through re-expression of ASS1 allows metabolic flexibility during renal cancer progression.

Neoadjuvant chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer, however, response can be limited by development of toxicities. Here, the authors conducted metabolomics on patients with locally advanced rectal cancer enrolled in a phase III clinical study and identify serum metabolites associated with treatment response.

Here, the authors present a method to build genetically personalised metabolic models across tissues to estimate individualised reaction fluxes. A fluxome-wide association study in UK Biobank identifies fluxes associated with metabolites and coronary artery disease.

Tree peony (Paeonia ostii) has the largest chromosome of any sequenced plants to date. Here, the authors assemble its genome and reveal the association of a list of candidate genes with fatty acid biosynthesis and the possible contribution of transposon and histone expansion to maintain the giga-chromosomes.

Four T2D subtypes were previously identified: severe insulin deficient, severe insulin resistant, mild obesity-related, and mild age-related diabetes. Here, the authors show that these subtypes can be translated to an Arabic population and identify distinct subtype-specific metabolic and proteomic signatures.

Chronic hyperglycemia impairs insulin secretion from pancreatic beta cells in diabetes. Here, the authors reveal that a glucose metabolite is responsible and show lowering glucose metabolism during hyperglycemia prevents loss of beta-cell function.

Itaconate has been identified as an immunomodulatory metabolite produced by activated macrophages, but methods for detecting itaconate in live cells are lacking. Here, the authors develop a fluorescent biosensor named BioITA for detecting itaconate in subcellular compartments of living macrophages.

Unknown metabolite annotation is a grand challenge in untargeted metabolomics. Here, the authors develop knowledge-guided multi-layer networking (KGMN) to enable global metabolite annotation from knowns to unknowns in untargeted metabolomics.

How dietary restriction increases longevity is still not fully understood. Here, the authors demonstrate that L-threonine is an essential mediator of dietary restriction that prevents age-induced ferroptosis and that dietary supplementation promotes healthy ageing.

Here, Dekkers et al. characterize associations of 1528 gut metagenomic species with the plasma metabolome in 8583 participants of the SCAPIS Study, and find that gut microbiota explain up to 58% of the variance of individual plasma metabolites.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

The genomes of filamentous fungi, such as Aspergillus, include many biosynthetic gene clusters of unknown function. Here, the authors show that copper starvation induces expression of an enzyme that generates a valine-derived isocyanide participating in two different pathways, for biosynthesis of acylated sugar alcohols and modified ergot alkaloids.

Bioactivity-guided isolation of specialized metabolites is an iterative process. Here, the authors demonstrate a native metabolomics approach that allows for fast screening of complex metabolite extracts against a protein of interest and simultaneous structure annotation.

Reproducibility, traceability, and transparency have been long-standing issues in metabolomics data analysis. Here, the authors present tidyMass, an R-based computational framework that allows designing traceable, shareable, and reproducible data processing and analysis workflows for untargeted metabolomics.

Kidney metabolism in disease is important but not well understood. Here, using isotope-guided metabolomics, the authors show that lysine’s metabolic activity conveys kidney protection in hypertension through accelerated metabolism and physiological effects on tubular function.

The molecular mechanisms ensuring the specialized structure of small intestinal villus tip blood vessels are incompletely understood. Here the authors show that ADAMTS18⁺ telocytes maintain a “just-right” level and location of VEGFA signaling on intestinal villus blood vessels, thereby ensuring the presence of endothelial fenestrae for nutrient absorption, while avoiding excessive leakiness and destabilization of villus tip epithelial structures.

Cytochrome P450s drive the structural diversity of plant alkaloids, many of which have biotechnological uses. Here the authors use reverse genetics and metabolomics to identify two Atropa belladonna cytochrome P450s that synthesize pseudotropine-derived alkaloids.

Potassium channels and membrane potential may influence macrophage function during inflammation. Here the authors show that the Kir2.1 potassium channel affects macrophage metabolism by altering cell surface retention of nutrient transporters and subsequently regulates inflammatory disease responses.

Stable-isotope tracing allows quantifying metabolic activity by measuring isotopically labeled metabolites, but its metabolome coverage has been limited. Here, the authors develop a global isotope tracing approach with metabolome-wide coverage and use it to characterize metabolic activities in aging Drosophila.

Mammalian embryogenesis relies on glycolysis and oxidative phosphorylation, but understanding of the dynamics of metabolic regulation in the postimplantation embryo in vivo remains elusive. Here the authors compile single-cell embryo profiling data in six mammalian species and reveal a conserved metabolic programme despite different implantation modes.

The presence of cancer can induce systemic disruption of the host homeostasis. Here, the authors show that different solid tumours remotely increase hepatic nicotinamide-Nmethyltransferase disrupting the host urea cycle metabolism in the liver.

Pulmonary hypertension is a fatal disease that causes right heart failure due to pulmonary artery stenosis. Here, the authors find that ω-3 epoxides produced by the phospholipase PAF-AH2 in mast cells regulate pulmonary vascular remodeling.

Understanding how yeast organizes its functional proteome is a fundamental task in systems biology. Here, the authors conduct a multiomics analysis on yeast cells cultured with different growth rates, identifying a linear dependence of the functional proteome on the growth rate.

Nucleotides are essential for different biological processes and have been also associated to cancer development. Depleting cellular nucleotides is a strategy commonly employed to target cancers. Here, the authors show that purine depletion induces serine synthesis to promote cancer cell migration and metastasis.

Interrelating metabolites by their fragmentation spectra is central to metabolomics. Here the authors align fragmentation spectra with both statistical significance and allowance for multiple chemical differences using Significant Interrelation of MS/MS Ions via Laplacian Embedding (SIMILE).

Caloric restriction is a common approach to weight reduction, however, weight regain is common. Here the authors report that caloric restriction reduces the abundance of Parabacteroides distasonis in the gut and alters serum bile acid (BA) profile, which contribute to weight regain in mice.

Endoplasmic Reticulum stress induces cell non-autonomous Unfolded Protein Response (UPR) activation. Here the authors show that long-chain ceramides are secreted from muscle cells in extracellular vesicles and induce cell non-autonomous UPR activation in muscle cells in response to lipotoxcity.

The extraction of meaningful biological knowledge from high-throughput mass spectrometry data relies on limiting false discoveries to a manageable amount. Here the authors establish an automated, false discovery rate-controlled targeted analysis workflow for data-independent acquisition that enables a robust FDR estimation improving the comparability of results in the metabolomics field.

Bradyzoites are a quiescent form of Toxoplasma gondii enclosed in cysts during chronic infections. Here, Christiansen et al. develop a human myotube-based in vitro culture model of cysts that are infectious to mice and characterize their metabolism in comparison to fast replicating tachyzoites.

Untargeted mass spectrometry-based metabolomics can reveal new biochemistry, but data analysis is challenging. Here, the authors develop Metaboseek, an open-source software that facilitates metabolite discovery, and apply it to characterize fatty acid alpha-oxidation in C. elegans.

Coenzyme A (CoA) is an essential metabolite found in all organisms and its synthesis involves five conserved enzymatic steps and uses pantothenate (Pan) as a precursor. Here, Lunghi et al. examine the Pan synthesis pathway in Toxoplasma gondii and find that Pan is crucial for the establishment of chronic but not acute infection.

Glycerol-3-phosphate phosphatase is a recently discovered enzyme at the heart of metabolism. Here, the authors used C. elegans and showed that its activation promotes stress resistance, healthy aging and acts as a calorie restriction mimetic at normal food intake without altering fertility.

Oxylipins are lipid mediators generated during infection for regulating inflammatory responses, but how they are removed is not completely clear. Here the authors show that cellular oxylipin removal is linked to mitochondria β-oxidation by CPT1, a mitochondria lipid importer protein, to serve as a metabolic checkpoint for oxylipin homeostasis and inflammation.

In this study, the authors demonstrated that agents targeting skeletal muscle metabolism by modulating β₂-adrenergic receptor-dependent signaling may prove beneficial as novel antidiabetic drugs.

Nicotinamide riboside (NR) is a NAD + precursor exhibiting beneficial effects against aging. Here the authors demonstrate that orally administered NR increases NAD + levels in a diphasic manner and that bone marrow stromal cell antigen 1 plays a crucial role for NAD + synthesis from NR.

Metabolic reprogramming occurs during tumor progression. Here the authors decipher metabolic trajectories from preneoplasia to lung adenocarcinoma in tumor samples and identify plasma metabolites as potential predictive biomarkers for early detection.

Heteroplasmic mtDNA mutations cause disease in humans. Here, Chung et al find the PI3K-Akt-mTORC1 pathway constitutively activated in cells with the heteroplasmic m.3243 A > G mutation, and inhibition of the pathway cell autonomously reduces mutant mtDNA load and rescues mitochondrial bioenergetics.

RIPK1 is critical for normal development and cell death. Here, the authors identify a metabolic role for RIPK1 in aspartate homeostasis, as increased aspartate levels in RIPK1-deficient cells inhibits starvation-induced autophagy by ULK1.

The gut microbiota harbours neuroactive potential with links to neurological disorders. Here, the authors apply global metabolomics with an integrated annotation strategy to comparatively profile fecal, blood serum and cerebral cortical brain tissues of eight-week-old germ-free mice vs. age-matched specific-pathogen-free mice, providing a snapshot of the metabolome status linked to the gut-brain axis.