Plasma metabolic alterations in patients with severe obesity and non-alcoholic steatohepatitis.
Aliment Pharmacol Ther
; 51(3): 374-387, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31825539
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, ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Obesidade Mórbida
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Biomarcadores
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Metaboloma
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Hepatopatia Gordurosa não Alcoólica
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Aliment Pharmacol Ther
Assunto da revista:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Espanha