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ACS Chemical Neuroscience Aug 2021Neurometabolites are the ultimate gene products in the brain and the most precise biomolecular indicators of brain endophenotypes. Metabolomics is the only "omics" that...
Neurometabolites are the ultimate gene products in the brain and the most precise biomolecular indicators of brain endophenotypes. Metabolomics is the only "omics" that provides a moment-to-moment "snapshot" of brain circuits' biochemical activities in response to external stimuli within the context of specific genetic variations. Although the expression levels of neurometabolites are highly dynamic, the underlying metabolic processes are tightly regulated during brain development, maturation, and aging. Therefore, this study aimed to identify mouse brain metabolic profiles in neonatal and adult stages and reconstruct both the active metabolic network and the metabolic pathway functioning. Using high-throughput metabolomics and bioinformatics analyses, we show that the neonatal mouse brain has its distinct metabolomic signature, which differs from the adult brain. Furthermore, lipid metabolites showed the most profound changes between the neonatal and adult brain, with some lipid species reaching 1000-fold changes. There were trends of age-dependent increases and decreases among lipids and non-lipid metabolites, respectively. A few lipid metabolites such as HexCers and SHexCers were almost absent in neonatal brains, whereas other non-lipid metabolites such as homoarginine were absent in the adult brains. Several molecules that act as neurotransmitters/neuromodulators showed age-dependent levels, with adenosine and GABA exhibiting around 100- and 10-fold increases in the adult compared with the neonatal brain. Of particular interest is the observation that purine and pyrimidines nucleobases exhibited opposite age-dependent changes. Bioinformatics analysis revealed an enrichment of lipid biosynthesis pathways in metabolites, whose levels increased in adult brains. In contrast, pathways involved in the metabolism of amino acids, nucleobases, glucose (glycolysis), tricarboxylic acid cycle (TCA) were enriched in metabolites whose levels were higher in the neonatal brains. Many of these pathways are associated with pathological conditions, which can be predicted as early as the neonatal stage. Our study provides an initial age-related biochemical directory of the mouse brain and warrants further studies to identify temporal brain metabolome across the lifespan, particularly during adolescence and aging. Such neurometabolomic data may provide important insight about the onset and progression of neurological/psychiatric disorders and may ultimately lead to the development of precise diagnostic biomarkers and more effective preventive/therapeutic strategies.
Topics: Animals; Brain; Citric Acid Cycle; Metabolic Networks and Pathways; Metabolome; Metabolomics; Mice
PubMed: 34283556
DOI: 10.1021/acschemneuro.1c00259 -
Current Opinion in Chemical Biology Feb 2020Understanding the molecular mechanisms of endogenous and environmental metabolites is crucial for basic biology and drug discovery. With the genome, proteome, and... (Review)
Review
Understanding the molecular mechanisms of endogenous and environmental metabolites is crucial for basic biology and drug discovery. With the genome, proteome, and metabolome of many organisms being readily available, researchers now have the opportunity to dissect how key metabolites regulate complex cellular pathways in vivo. Nonetheless, characterizing the specific and functional protein targets of key metabolites associated with specific cellular phenotypes remains a major challenge. Innovations in chemical biology are now poised to address this fundamental limitation in physiology and disease. In this review, we highlight recent advances in chemoproteomics for targeted and proteome-wide analysis of metabolite-protein interactions that have enabled the discovery of unpredicted metabolite-protein interactions and facilitated the development of new small molecule therapeutics.
Topics: Humans; Metabolome; Metabolomics; Proteins; Proteome; Proteomics
PubMed: 31790852
DOI: 10.1016/j.cbpa.2019.10.008 -
Psychiatry Research Dec 2023Growing evidence suggests that major psychiatric disorders (MPDs) share common etiologies and pathological processes. However, the diagnosis is currently based on...
Growing evidence suggests that major psychiatric disorders (MPDs) share common etiologies and pathological processes. However, the diagnosis is currently based on descriptive symptoms, which ignores the underlying pathogenesis and hinders the development of clinical treatments. This highlights the urgency of characterizing molecular biomarkers and establishing objective diagnoses of MPDs. Here, we collected untargeted metabolomics, proteomics and DNA methylation data of 327 patients with MPDs, 131 individuals with genetic high risk and 146 healthy controls to explore the multi-omics characteristics of MPDs. First, differential metabolites (DMs) were identified and we classified MPD patients into 3 subtypes based on DMs. The subtypes showed distinct metabolomics, proteomics and DNA methylation signatures. Specifically, one subtype showed dysregulation of complement and coagulation proteins, while the DNA methylation showed abnormalities in chemical synapses and autophagy. Integrative analysis in metabolic pathways identified the important roles of the citrate cycle, sphingolipid metabolism and amino acid metabolism. Finally, we constructed prediction models based on the metabolites and proteomics that successfully captured the risks of MPD patients. Our study established molecular subtypes of MPDs and elucidated their biological heterogeneity through a multi-omics investigation. These results facilitate the understanding of pathological mechanisms and promote the diagnosis and prevention of MPDs.
Topics: Humans; Multiomics; Metabolome; Mental Disorders; Metabolomics; Proteomics
PubMed: 38006718
DOI: 10.1016/j.psychres.2023.115605 -
Journal of Magnetic Resonance (San... Sep 2019NMR has been used to perform metabolic studies, metabolic profiling and metabolomics in biofluids and tissues for more than 40 years. This close connection between... (Review)
Review
NMR has been used to perform metabolic studies, metabolic profiling and metabolomics in biofluids and tissues for more than 40 years. This close connection between metabolic measurements and NMR has flourished because of NMR's many unique strengths for characterizing the chemical composition of complex mixtures. However, a number of other technologies, including mass spectrometry, have appeared in the past few years that are encroaching on NMR's dominance in metabolomics and metabolic studies. In this brief review, some of the current strengths and existing limitations of NMR-based metabolomics are highlighted. Additionally, a number of recent advances in NMR hardware, methodology and software are also described and these advancements are used to speculate about where NMR-based metabolomics is going, what needs to be done to make it more popular and how it will evolve in the next 5-10 years.
Topics: Animals; Humans; Metabolome; Metabolomics; Nuclear Magnetic Resonance, Biomolecular
PubMed: 31377153
DOI: 10.1016/j.jmr.2019.07.013 -
Advances in Clinical Chemistry 2022Metabolism is a highly regulated process that provides nutrients to cells and essential building blocks for the synthesis of protein, DNA and other macromolecules. In... (Review)
Review
Metabolism is a highly regulated process that provides nutrients to cells and essential building blocks for the synthesis of protein, DNA and other macromolecules. In healthy biological systems, metabolism maintains a steady state in which the concentrations of metabolites are relatively constant yet are subject to metabolic demands and environmental stimuli. Rare genetic disorders, such as inborn errors of metabolism (IEM), cause defects in regulatory enzymes or proteins leading to metabolic pathway disruption and metabolite accumulation or deficiency. Traditionally, the laboratory diagnosis of IEMs has been limited to analytical methods that target specific metabolites such as amino acids and acyl carnitines. This approach is effective as a screening method for the most common IEM disorders but lacks the comprehensive coverage of metabolites that is necessary to identify rare disorders that present with nonspecific clinical symptoms. Fortunately, advancements in technology and data analytics has introduced a new field of study called metabolomics which has allowed scientists to perform comprehensive metabolite profiling of biological systems to provide insight into mechanism of action and gene function. Since metabolomics seeks to measure all small molecule metabolites in a biological specimen, it provides an innovative approach to evaluating disease in patients with rare genetic disorders. In this review we provide insight into the appropriate application of metabolomics in clinical settings. We discuss the advantages and limitations of the method and provide details related to the technology, data analytics and statistical modeling required for metabolomic profiling of patients with IEMs.
Topics: Biomarkers; Humans; Metabolic Networks and Pathways; Metabolism, Inborn Errors; Metabolome; Metabolomics
PubMed: 35337606
DOI: 10.1016/bs.acc.2021.09.001 -
Molecules (Basel, Switzerland) Nov 2023Wine has a rich history dating back to 2200 BC, originally recognized for its medicinal properties. Today, with the aid of advanced technologies like metabolomics and... (Review)
Review
Wine has a rich history dating back to 2200 BC, originally recognized for its medicinal properties. Today, with the aid of advanced technologies like metabolomics and sophisticated analytical techniques, we have gained remarkable insights into the molecular-level changes induced by wine consumption in the human organism. This review embarks on a comprehensive exploration of the alterations in human metabolome associated with wine consumption. A great number of 51 studies from the last 25 years were reviewed; these studies systematically investigated shifts in metabolic profiles within blood, urine, and feces samples, encompassing both short-term and long-term studies of the consumption of wine and wine derivatives. Significant metabolic alterations were observed in a wide variety of metabolites belonging to different compound classes, such as phenolic compounds, lipids, organic acids, and amino acids, among others. Within these classes, both endogenous metabolites as well as diet-related metabolites that exhibited up-regulation or down-regulation following wine consumption were included. The up-regulation of short-chain fatty acids and the down-regulation of sphingomyelins after wine intake, as well as the up-regulation of gut microbial fermentation metabolites like vanillic and syringic acid are some of the most important findings reported in the reviewed literature. Our results confirm the intact passage of certain wine compounds, such as tartaric acid and other wine acids, to the human organism. In an era where the health effects of wine consumption are of growing interest, this review offers a holistic perspective on the metabolic underpinnings of this centuries-old tradition.
Topics: Humans; Wine; Metabolome; Phenols; Metabolomics; Diet
PubMed: 38005338
DOI: 10.3390/molecules28227616 -
Current Nutrition Reports Sep 2019Metabolomics offers several opportunities for advancement in nutritional cancer epidemiology; however, numerous research gaps and challenges remain. This narrative... (Review)
Review
PURPOSE OF REVIEW
Metabolomics offers several opportunities for advancement in nutritional cancer epidemiology; however, numerous research gaps and challenges remain. This narrative review summarizes current research, challenges, and future directions for epidemiologic studies of nutritional metabolomics and cancer.
RECENT FINDINGS
Although many studies have used metabolomics to investigate either dietary exposures or cancer, few studies have explicitly investigated diet-cancer relationships using metabolomics. Most studies have been relatively small (≤ ~ 250 cases) or have assessed a limited number of nutritional metabolites (e.g., coffee or alcohol-related metabolites). Nutritional metabolomic investigations of cancer face several challenges in study design; biospecimen selection, handling, and processing; diet and metabolite measurement; statistical analyses; and data sharing and synthesis. More metabolomics studies linking dietary exposures to cancer risk, prognosis, and survival are needed, as are biomarker validation studies, longitudinal analyses, and methodological studies. Despite the remaining challenges, metabolomics offers a promising avenue for future dietary cancer research.
Topics: Biomarkers, Tumor; Diet; Epidemiologic Studies; Humans; Metabolome; Metabolomics; Neoplasms; Nutritional Physiological Phenomena; Prognosis
PubMed: 31129888
DOI: 10.1007/s13668-019-00279-z -
Methods in Molecular Biology (Clifton,... 2021Enzymes fuel the biochemical activities of all cells. Their substrates and products thus represent a potential window into the physiologic state of a cell. Metabolomics...
Enzymes fuel the biochemical activities of all cells. Their substrates and products thus represent a potential window into the physiologic state of a cell. Metabolomics focuses on the global, or systems-level, study of small molecules in a given biological system and has thus provided an experimental tool with which to study cellular physiology, including the biochemistry within pathogenic microorganisms. While metabolomic studies of Mycobacterium tuberculosis are still in their infancy, recent studies have begun to deliver unique insights into the composition, organization, activity, and regulation of the bacterium's physiologic network not accessible by other approaches. Here, we outline practical methods for the culture, collection, and analysis of metabolomic samples from M. tuberculosis that emphasize minimally perturbing sample handling, broad and native metabolite recovery, and sensitive, biologically agnostic metabolite detection.
Topics: Chromatography, Liquid; Humans; Mass Spectrometry; Metabolome; Metabolomics; Mycobacterium tuberculosis
PubMed: 34235671
DOI: 10.1007/978-1-0716-1460-0_25 -
Emerging Topics in Life Sciences May 2021Untargeted metabolomics enables the identification of key changes to standard pathways, but also aids in revealing other important and possibly novel metabolites or... (Review)
Review
Untargeted metabolomics enables the identification of key changes to standard pathways, but also aids in revealing other important and possibly novel metabolites or pathways for further analysis. Much progress has been made in this field over the past decade and yet plant metabolomics seems to still be an emerging approach because of the high complexity of plant metabolites and the number one challenge of untargeted metabolomics, metabolite identification. This final and critical stage remains the focus of current research. The intention of this review is to give a brief current state of LC-MS based untargeted metabolomics approaches for plant specific samples and to review the emerging solutions in mass spectrometer hardware and computational tools that can help predict a compound's molecular structure to improve the identification rate.
Topics: Chromatography, Liquid; Metabolome; Metabolomics; Systems Biology; Tandem Mass Spectrometry
PubMed: 33704399
DOI: 10.1042/ETLS20200271 -
International Journal of Molecular... Oct 2021Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical... (Review)
Review
Metabolomics-based technologies map in vivo biochemical changes that may be used as early indicators of pathological abnormalities prior to the development of clinical symptoms in neurological conditions. Metabolomics may also reveal biochemical pathways implicated in tissue dysfunction and damage and thus assist in the development of novel targeted therapeutics for neuroinflammation and neurodegeneration. Metabolomics holds promise as a non-invasive, high-throughput and cost-effective tool for early diagnosis, follow-up and monitoring of treatment response in multiple sclerosis (MS), in combination with clinical and imaging measures. In this review, we offer evidence in support of the potential of metabolomics as a biomarker and drug discovery tool in MS. We also use pathway analysis of metabolites that are described as potential biomarkers in the literature of MS biofluids to identify the most promising molecules and upstream regulators, and show novel, still unexplored metabolic pathways, whose investigation may open novel avenues of research.
Topics: Animals; Biomarkers; Humans; Metabolome; Metabolomics; Multiple Sclerosis; Prognosis
PubMed: 34681773
DOI: 10.3390/ijms222011112