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Metabolites, Volume 7, Issue 4 (December 2017)

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Research

Open AccessArticle Specificities of Human Hepatocellular Carcinoma Developed on Non-Alcoholic Fatty Liver Disease in Absence of Cirrhosis Revealed by Tissue Extracts 1H-NMR Spectroscopy
Metabolites 2017, 7(4), 49; doi:10.3390/metabo7040049
Received: 29 August 2017 / Revised: 18 September 2017 / Accepted: 20 September 2017 / Published: 22 September 2017
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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
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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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Open AccessArticle Exometabolomic Analysis of Cross-Feeding Metabolites
Metabolites 2017, 7(4), 50; doi:10.3390/metabo7040050
Received: 12 September 2017 / Revised: 1 October 2017 / Accepted: 2 October 2017 / Published: 4 October 2017
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Abstract
Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we
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Microbial consortia have the potential to perform complex, industrially important tasks. The design of microbial consortia requires knowledge of the substrate preferences and metabolic outputs of each member, to allow understanding of potential interactions such as competition and beneficial metabolic exchange. Here, we used exometabolite profiling to follow the resource processing by a microbial co-culture of two biotechnologically relevant microbes, the bacterial cellulose degrader Cellulomonas fimi, and the oleaginous yeast Yarrowia lipolytica. We characterized the substrate preferences of the two strains on compounds typically found in lignocellulose hydrolysates. This allowed prediction that specific sugars resulting from hemicellulose polysaccharide degradation by C. fimi may serve as a cross-feeding metabolites to Y. lipolytica in co-culture. We also showed that products of ionic liquid-treated switchgrass lignocellulose degradation by C. fimi were channeled to Y. lipolytica in a co-culture. Additionally, we observed metabolites, such as shikimic acid accumulating in the co-culture supernatants, suggesting the potential for producing interesting co-products. Insights gained from characterizing the exometabolite profiles of individual and co-cultures of the two strains can help to refine this interaction, and guide strategies for making this an industrially viable co-culture to produce valuable products from lignocellulose material. Full article
(This article belongs to the Special Issue Environmental Metabolomics)
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Open AccessArticle Robust Regression Analysis of GCMS Data Reveals Differential Rewiring of Metabolic Networks in Hepatitis B and C Patients
Metabolites 2017, 7(4), 51; doi:10.3390/metabo7040051
Received: 11 September 2017 / Revised: 30 September 2017 / Accepted: 5 October 2017 / Published: 8 October 2017
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Abstract
About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of
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About one in 15 of the world’s population is chronically infected with either hepatitis virus B (HBV) or C (HCV), with enormous public health consequences. The metabolic alterations caused by these infections have never been directly compared and contrasted. We investigated groups of HBV-positive, HCV-positive, and uninfected healthy controls using gas chromatography-mass spectrometry analyses of their plasma and urine. A robust regression analysis of the metabolite data was conducted to reveal correlations between metabolite pairs. Ten metabolite correlations appeared for HBV plasma and urine, with 18 for HCV plasma and urine, none of which were present in the controls. Metabolic perturbation networks were constructed, which permitted a differential view of the HBV- and HCV-infected liver. HBV hepatitis was consistent with enhanced glucose uptake, glycolysis, and pentose phosphate pathway metabolism, the latter using xylitol and producing threonic acid, which may also be imported by glucose transporters. HCV hepatitis was consistent with impaired glucose uptake, glycolysis, and pentose phosphate pathway metabolism, with the tricarboxylic acid pathway fueled by branched-chain amino acids feeding gluconeogenesis and the hepatocellular loss of glucose, which most probably contributed to hyperglycemia. It is concluded that robust regression analyses can uncover metabolic rewiring in disease states. Full article
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