Plasma metabolic alterations in patients with severe obesity and non-alcoholic steatohepatitis
Aliment Pharmacol Ther. 2020 Feb;51(3):374-387. doi: 10.1111/apt.15606. Epub 2019 Dec 11.
ABSTRACT
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.
PMID:31825539 | DOI:10.1111/apt.15606
