Metabolomics and Its Application in Human Diseases

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (31 July 2017) | Viewed by 17894

Special Issue Editor


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Guest Editor
Department of Precision Medicine, Berg Pharma, Framingham, MA 01701, USA
Interests: discovery and clinical metabolomics; biomarkers; systems biology; AI; multi-omics; separation science; mass spectrometry
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Special Issue Information

Dear Colleagues,

Metabolomics is a rapidly growing and promising field facilitating innovations and discoveries in the life sciences and in biomedical research. Metabolomics has emerged as an essential tool for studying metabolic processes, the stratification of patients, as well as illuminating the fundamental metabolic alterations in disease onset, progression, or response to therapeutic intervention. Standalone, or as a part of multi-omics protocols, metabolomics contributes significantly to putting into practice the principles of precision medicine. Therefore, this Special Issue of Metabolites is tailored to the biomedical community. It combines timely reviews discussing the challenges associated with metabolomics and its integration with other omics methods and protocols, applied towards human disease studies with research articles presenting new findings and results related to metabolomics application in research related to human diseases.

Dr. Vladimir V. Tolstikov
Guest Editor

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Keywords

  • metabolites
  • metabolomics
  • pathway
  • biomarker
  • metabolism
  • diagnostic
  • disease
  • clinical
  • drug
  • pharmaceutical
  • precision medicine

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Published Papers (3 papers)

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Research

2692 KiB  
Article
Specificities of Human Hepatocellular Carcinoma Developed on Non-Alcoholic Fatty Liver Disease in Absence of Cirrhosis Revealed by Tissue Extracts 1H-NMR Spectroscopy
by Camille Teilhet, Daniel Morvan, Juliette Joubert-Zakeyh, Anne-Sophie Biesse, Bruno Pereira, Sylvie Massoulier, Pierre Dechelotte, Denis Pezet, Emmanuel Buc, Géraldine Lamblin, Michel Peoc’h, Jack Porcheron, Marie-Paule Vasson, Armando Abergel and Aicha Demidem
Metabolites 2017, 7(4), 49; https://doi.org/10.3390/metabo7040049 - 22 Sep 2017
Cited by 21 | Viewed by 4772
Abstract
There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD. To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated [...] Read more.
There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD. To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated with NAFLD and HCC associated with cirrhosis. The study included 28 pairs of HCC tissue versus distant Non-Tumoral Tissue (NTT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis (n = 9), normal liver (n = 6) and NAFLD (n = 13). Metabolomics was performed using 1H-NMR Spectroscopy on tissue extracts and combined to multivariate statistical analysis. In HCC compared to NTT, statistical models showed high levels of lactate and phosphocholine, and low level of glucose. Shared and Unique Structures (SUS) plots were performed to remove the impact of underlying disease on the metabolic profile of HCC. HCC-cirrhosis was characterized by high levels of β-hydroxybutyrate, tyrosine, phenylalanine and histidine whereas HCC-NAFLD was characterized by high levels of glutamine/glutamate. In addition, the overexpression glutamine/glutamate on HCC-NAFLD was confirmed by both Glutamine Synthetase (GS) immuno-staining and NMR-spectroscopy glutamine quantification. This study provides evidence of metabolic specificities of HCC associated with non-cirrhotic NAFLD versus HCC associated with cirrhosis. These alterations could suggest activation of glutamine synthetase pathway in HCC-NAFLD and mitochondrial dysfunction in HCC-cirrhosis, that may be part of specific carcinogenic processes. Full article
(This article belongs to the Special Issue Metabolomics and Its Application in Human Diseases)
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1108 KiB  
Article
Metabolomics Analysis of Urine Samples from Children after Acetaminophen Overdose
by Laura K. Schnackenberg, Jinchun Sun, Sudeepa Bhattacharyya, Pritmohinder Gill, Laura P. James and Richard D. Beger
Metabolites 2017, 7(3), 46; https://doi.org/10.3390/metabo7030046 - 6 Sep 2017
Cited by 15 | Viewed by 6315
Abstract
Acetaminophen (APAP), a commonly used over-the-counter analgesic, accounts for approximately fifty percent of the cases of acute liver failure (ALF) in the United States due to overdose, with over half of those unintentional. Current clinical approaches for assessing APAP overdose rely on identifying [...] Read more.
Acetaminophen (APAP), a commonly used over-the-counter analgesic, accounts for approximately fifty percent of the cases of acute liver failure (ALF) in the United States due to overdose, with over half of those unintentional. Current clinical approaches for assessing APAP overdose rely on identifying the precise time of overdose and quantitating acetaminophen alanine aminotransferase (ALT) levels in peripheral blood. Novel specific and sensitive biomarkers may provide additional information regarding patient status post overdose. Previous non-clinical metabolomics studies identified potential urinary biomarkers of APAP-induced hepatotoxicity and metabolites involved pathways of tricarboxylic acid cycle, ketone metabolism, and tryptophan metabolism. In this study, biomarkers identified in the previous non-clinical study were evaluated in urine samples collected from healthy subjects (N = 6, median age 14.08 years) and overdose patients (N = 13, median age 13.91 years) as part of an IRB-approved multicenter study of APAP toxicity in children. The clinical results identified metabolites from pathways previously noted, and pathway analysis indicated analogous pathways were significantly altered in both the rats and humans after APAP overdose. The results suggest a metabolomics approach may enable the discovery of specific, translational biomarkers of drug-induced hepatotoxicity that may aid in the assessment of patients. Full article
(This article belongs to the Special Issue Metabolomics and Its Application in Human Diseases)
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Article
Metabolomics with Nuclear Magnetic Resonance Spectroscopy in a Drosophila melanogaster Model of Surviving Sepsis
by Veli Bakalov, Roland Amathieu, Mohamed N. Triba, Marie-Jeanne Clément, Laura Reyes Uribe, Laurence Le Moyec and Ata Murat Kaynar
Metabolites 2016, 6(4), 47; https://doi.org/10.3390/metabo6040047 - 21 Dec 2016
Cited by 15 | Viewed by 6236
Abstract
Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology [...] Read more.
Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles. We used a model of percutaneous infection in Drosophila melanogaster to mimic sepsis. We had three experimental groups: sepsis survivors (infected with Staphylococcus aureus and treated with oral linezolid), sham (pricked with an aseptic needle), and unmanipulated (positive control). We performed metabolic measurements seven days after sepsis. We then implemented metabolites detected in NMR spectra into the MetExplore web server in order to identify the metabolic pathway alterations in sepsis surviving Drosophila. Our NMR metabolomic approach in a Drosophila model of recovery from sepsis clearly distinguished between all three groups and showed two different metabolomic signatures of inflammation. Sham flies had decreased levels of maltose, alanine, and glutamine, while their level of choline was increased. Sepsis survivors had a metabolic signature characterized by decreased glucose, maltose, tyrosine, beta-alanine, acetate, glutamine, and succinate. Full article
(This article belongs to the Special Issue Metabolomics and Its Application in Human Diseases)
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