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Plasma metabolic alterations in patients with severe obesity and non‐alcoholic steatohepatitis.
- Source :
- Alimentary Pharmacology & Therapeutics; Feb2020, Vol. 51 Issue 3, p374-387, 14p, 2 Color Photographs, 2 Diagrams, 2 Charts, 1 Graph
- Publication Year :
- 2020
-
Abstract
- Summary: Background: Obesity can influence hepatic mitochondrial function, and cause non‐alcoholic steatohepatitis (NASH). Diagnosis and follow‐up rely on invasive liver biopsy so blood‐based markers are urgently required. Aim: To investigate whether values of circulating metabolites from energy and one‐carbon (1‐C) metabolism may: (a) reflect hepatic mitochondrial flexibility failure and (b) act as NASH biomarkers. Methods: Patients with severe obesity undergoing bariatric surgery (n = 270) were investigated using quantitative targeted plasma metabolomics. Comparisons were with non‐obese controls without liver disease (n = 50). Obese patients with NASH (n = 53) and without NASH (n = 130) representing extreme groups of liver disease were assessed to test the diagnostic ability of the measured circulating metabolites. Paired liver biopsy and plasma samples from NASH patients were available 1 year post‐surgery and were evaluated to monitor metabolomic changes with liver damage resolution. Results: We identified correlations between human liver metabolism and obesity. High‐plasma α‐ketoglutarate (α‐KG) and lactate concentrations in NASH patients indicating citric acid cycle replenishment via glutaminolysis might also be a crucial point in NASH onset. Plasma measurements of α‐KG, β‐hydroxybutyrate, pyruvate and oxaloacetate reduced the uncertainty in clinical diagnosis of NASH [area under receiver operating characteristic curve (AUC) of 0.826] and predicted NASH resolution without ambiguity (AUC of 0.999). Conclusion: Changes in plasma mitochondrial metabolites appear to be associated with NASH. These metabolic responses may be dynamically remodelled following resolution of liver damage through massive weight loss. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 02692813
- Volume :
- 51
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Alimentary Pharmacology & Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 141206540
- Full Text :
- https://doi.org/10.1111/apt.15606