title: Mapping of the circulating metabolome reveals α-ketoglutarate as a predictor of morbid obesity-associated non-alcoholic fatty liver disease.
abstract: BACKGROUND
  Obesity severely affects human health, and the accompanying non-alcoholic fatty liver disease (NAFLD) is associated with high morbidity and mortality. Rapid and non-invasive methods to detect this condition may substantially improve clinical care.
  
  
  METHODS
  We used liquid and gas chromatography-quadruple time-of-flight-mass spectrometry (LC/GC-QTOF-MS) analysis in a non-targeted metabolomics approach on the plasma from morbidly obese patients undergoing bariatric surgery to gain a comprehensive measure of metabolite levels. On the basis of these findings, we developed a method (GC-QTOF-MS) for the accurate quantification of plasma α-ketoglutarate to explore its potential as a novel biomarker for the detection of NAFLD.
  
  
  RESULTS
  Plasma biochemical differences were observed between patients with and without NAFLD indicating that the accumulation of lipids in hepatocytes decreased β-oxidation energy production, reduced liver function and altered glucose metabolism. The results obtained from the plasma analysis suggest pathophysiological insights that link lipid and glucose disturbances with α-ketoglutarate. Plasma α-ketoglutarate levels are significantly increased in obese patients compared with lean controls. Among obese patients, the measurement of this metabolite differentiates between those with or without NAFLD. Data from the liver were consistent with data from plasma. Clinical utility was assessed, and the results revealed that plasma α-ketoglutarate is a fair-to-good biomarker in patients (n=230). Other common laboratory liver tests used in routine application did not favourably compare.
  
  
  CONCLUSIONS
  Plasma α-ketoglutarate is superior to common liver function tests in obese patients as a surrogate biomarker of NAFLD. The measurement of this biomarker may potentiate the search for a therapeutic approach, may decrease the need for liver biopsy and may be useful in the assessment of disease progression.
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Rodríguez-Gallego
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Guirro
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Riera-Borrull
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Hernández-Aguilera
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Mariné-Casadó
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Fernández-Arroyo
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Beltrán-Debón
authors.affiliation: Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: F
authors.initials: F
authors.lastname: Sabench
authors.affiliation: Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Hernández
authors.affiliation: Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: D
authors.initials: D
authors.lastname: del Castillo
authors.affiliation: Catalan Institute of Oncology and Girona Biomedical Research Institute, Girona, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Menendez
authors.affiliation: Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Camps
authors.affiliation: Center for Omics Sciences, Reus, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Ras
authors.affiliation: 1] Department of Biochemistry and Biotechnology, Universitat Rovira i Virgili. Centre Tecnològic de Nutrició i Salut, Reus, Spain [2] Campus of International Excellence Southern Catalonia, Tarragona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Arola
authors.affiliation: 1] Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain [2] Campus of International Excellence Southern Catalonia, Tarragona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Joven
mesh_terms: D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D018450:Disease Progression; D006801:Humans; D007656:Ketoglutaric Acids / Q000097:blood*; D050356:Lipid Metabolism; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D009767:Obesity, Morbid / Q000097:blood* / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D007656:Ketoglutaric Acids