title: Increased Circulating Levels of Alpha-Ketoglutarate in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.
abstract: Non-alcoholic fatty liver disease (NAFLD) causes a wide spectrum of liver damage, ranging from simple steatosis to cirrhosis. However, simple steatosis (SS) and steatohepatitis (NASH) cannot yet be distinguished by clinical or laboratory features. The aim of this study was to assess the relationship between alpha-ketoglutarate and the degrees of NAFLD in morbidly obese patients.
  
  
  
  We used a gas chromatography-quadruple time-of-flight-mass spectrometry analysis to quantify alpha-ketoglutarate in serum from normal-weight subjects (n = 30) and morbidly obese women (n = 97) with or without NAFLD.
  
  
  
  We found that serum levels of alpha-ketoglutarate were significantly higher in morbidly obese women than in normal-weight women. We showed that circulating levels of alpha-ketoglutarate were lower in lean controls and morbidly obese patients without NAFLD. We also found that alpha-ketoglutarate serum levels were higher in both SS and NASH than in normal liver of morbidly obese patients. However, there was no difference between SS and NASH. Moreover, we observed that circulating levels of alpha-ketoglutarate were associated with glucose metabolism parameters, lipid profile, hepatic enzymes and steatosis degree. In addition, diagnostic performance of alpha-ketoglutarate has been analyzed in NAFLD patients. The AUROC curves from patients with liver steatosis exhibited an acceptable clinical utility. Finally, we showed that the combination of biomarkers (AST, ALT and alpha-ketoglutarate) had the highest accuracy in diagnosing liver steatosis.
  
  
  
  These findings suggest that alpha-ketoglutarate can determine the presence of non-alcoholic fatty liver in morbidly obese patients but it is not valid a biomarker for NASH.
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)- Medicina Aplicada. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007, Tarragona, Spain.
authors.forename: Gemma
authors.identifier: 0000-0002-1924-9231
authors.initials: G
authors.lastname: Aragonès
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)- Medicina Aplicada. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007, Tarragona, Spain.|Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona. Mallafré Guasch, 4, 43007, Tarragona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Auguet
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)- Medicina Aplicada. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007, Tarragona, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Berlanga
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)- Medicina Aplicada. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007, Tarragona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Guiu-Jurado
authors.affiliation: Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona. Mallafré Guasch, 4, 43007, Tarragona, Spain.
authors.forename: Salomé
authors.initials: S
authors.lastname: Martinez
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)- Medicina Aplicada. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007, Tarragona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Armengol
authors.affiliation: Servei de Cirurgia. Hospital Sant Joan de Reus. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, 43204, Reus, Spain.
authors.forename: Fàtima
authors.initials: F
authors.lastname: Sabench
authors.affiliation: Group of Research on Omic Methodologies (GROM). Centre for Omic Sciences (COS), Reus, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Ras
authors.affiliation: Servei de Cirurgia. Hospital Sant Joan de Reus. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, 43204, Reus, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Hernandez
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)- Medicina Aplicada. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007, Tarragona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Aguilar
authors.affiliation: Servei Medicina Interna, Hospital Sant Joan de Reus. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, 43204, Reus, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Colom
authors.affiliation: Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona. Mallafré Guasch, 4, 43007, Tarragona, Spain.
authors.forename: Joan Josep
authors.initials: JJ
authors.lastname: Sirvent
authors.affiliation: Servei de Cirurgia. Hospital Sant Joan de Reus. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, 43204, Reus, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Del Castillo
authors.affiliation: Grup de Recerca GEMMAIR (AGAUR)- Medicina Aplicada. Departament de Medicina i Cirurgia. Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili (IISPV), 43007, Tarragona, Spain.|Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona. Mallafré Guasch, 4, 43007, Tarragona, Spain.
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Richart
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007656:Ketoglutaric Acids / Q000097:blood*; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000175:diagnosis*; D009767:Obesity, Morbid / Q000097:blood*
chemical_list: D015415:Biomarkers; D007656:Ketoglutaric Acids