Plasma Krebs Cycle Intermediates in Nonalcoholic Fatty Liver Disease
Open Access
- 22 January 2020
- journal article
- research article
- Published by MDPI AG in Journal of Clinical Medicine
- Vol. 9 (2), 314
- https://doi.org/10.3390/jcm9020314
Abstract
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.This publication has 45 references indexed in Scilit:
- Elevated citrate levels in non‐alcoholic fatty liver disease: The potential of citrate to promote radical productionFEBS Letters, 2013
- Serum bilirubin levels are inversely associated with nonalcoholic fatty liver diseaseClinical and Molecular Hepatology, 2012
- Chronic Exposure to a High-Fat Diet Induces Hepatic Steatosis, Impairs Nitric Oxide Bioavailability, and Modifies the Mitochondrial Proteome in MiceAntioxidants and Redox Signaling, 2011
- Endpoints and clinical trial design for nonalcoholic steatohepatitisHepatology, 2011
- Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent modelJournal of Hepatology, 2010
- Nonalcoholic fatty liver disease and mitochondrial dysfunctionWorld Journal of Gastroenterology, 2008
- Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitisHepatology, 2003
- Defective hepatic mitochondrial respiratory chain in patients with nonalcoholic steatohepatitisHepatology, 2003
- Serum leptin level can be a negative marker of hepatocyte damage in nonalcoholic fatty liverThe Esophagus, 2003
- Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic ConferenceHepatology, 2003