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Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease

Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies...

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Autores principales: Sandlers, Yana, Shah, Rohan R., Pearce, Ryan W., Dasarathy, Jaividhya, McCullough, Arthur J., Dasarathy, Srinivasan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073566/
https://www.ncbi.nlm.nih.gov/pubmed/31979094
http://dx.doi.org/10.3390/jcm9020314
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author Sandlers, Yana
Shah, Rohan R.
Pearce, Ryan W.
Dasarathy, Jaividhya
McCullough, Arthur J.
Dasarathy, Srinivasan
author_facet Sandlers, Yana
Shah, Rohan R.
Pearce, Ryan W.
Dasarathy, Jaividhya
McCullough, Arthur J.
Dasarathy, Srinivasan
author_sort Sandlers, Yana
collection PubMed
description Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD (n = 22) and matched control (n = 67) cohorts. Circulating levels of isocitrate and citrate were significantly (p < 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson’s correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted.
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spelling pubmed-70735662020-03-20 Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease Sandlers, Yana Shah, Rohan R. Pearce, Ryan W. Dasarathy, Jaividhya McCullough, Arthur J. Dasarathy, Srinivasan J Clin Med Article Nonalcoholic liver disease (NAFLD) is manifested with a wide spectrum of clinical symptoms and is closely associated with the metabolic syndrome, inflammation, and mitochondrial dysfunction. Although the mechanism of mitochondrial dysfunction in NAFLD is still not fully elucidated, multiple studies have demonstrated evidence of molecular, biochemical, and biophysical mitochondrial abnormalities in NAFLD. Given the association between NAFLD and mitochondrial dysfunction, the aim of this study is to analyze circulating levels of Krebs cycle intermediates in a cohort of NAFLD-affected individuals and matching healthy controls and to correlate our findings with the liver function metrics. Standard serum biochemistry and Krebs cycle intermediates were analyzed in NAFLD (n = 22) and matched control (n = 67) cohorts. Circulating levels of isocitrate and citrate were significantly (p < 0.05) elevated in the NAFLD cohort of patients. The area under the curve (AUROC) for these two metabolites exhibited a moderate clinical utility. Correlations between plasma Krebs cycle intermediates and standard clinical plasma metrics were explored by Pearson’s correlation coefficient. The data obtained for plasma Krebs cycle intermediates suggest pathophysiological insights that link mitochondrial dysfunction with NAFLD. Our findings reveal that plasma isocitrate and citrate can discriminate between normal and NAFLD cohorts and can be utilized as noninvasive markers of mitochondrial dysfunction in NAFLD. Future studies with large populations at different NAFLD stages are warranted. MDPI 2020-01-22 /pmc/articles/PMC7073566/ /pubmed/31979094 http://dx.doi.org/10.3390/jcm9020314 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sandlers, Yana
Shah, Rohan R.
Pearce, Ryan W.
Dasarathy, Jaividhya
McCullough, Arthur J.
Dasarathy, Srinivasan
Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
title Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
title_full Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
title_fullStr Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
title_full_unstemmed Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
title_short Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
title_sort plasma krebs cycle intermediates in nonalcoholic fatty liver disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073566/
https://www.ncbi.nlm.nih.gov/pubmed/31979094
http://dx.doi.org/10.3390/jcm9020314
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