E Rodríguez-Gallego1, M Guirro1, M Riera-Borrull1, A Hernández-Aguilera1, R Mariné-Casadó1, S Fernández-Arroyo1, R Beltrán-Debón1, F Sabench2, M Hernández2, D del Castillo2, J A Menendez3, J Camps1, R Ras4, L Arola5, J Joven6. 1. Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain. 2. Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain. 3. Catalan Institute of Oncology and Girona Biomedical Research Institute, Girona, Spain. 4. Center for Omics Sciences, Reus, Spain. 5. 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. 6. 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.
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. CONCLUSION: 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.
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 obesepatients 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 obesepatients compared with lean controls. Among obesepatients, 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. CONCLUSION: Plasma α-ketoglutarate is superior to common liver function tests in obesepatients 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: M Koch; S Freitag-Wolf; S Schlesinger; J Borggrefe; J R Hov; M K Jensen; J Pick; M R P Markus; T Höpfner; G Jacobs; S Siegert; A Artati; G Kastenmüller; W Römisch-Margl; J Adamski; T Illig; M Nothnagel; T H Karlsen; S Schreiber; A Franke; M Krawczak; U Nöthlings; W Lieb Journal: Eur J Clin Nutr Date: 2017-04-05 Impact factor: 4.016
Authors: Gabriela Paredes-Turrubiarte; Antonio González-Chávez; Ruy Pérez-Tamayo; Beatriz Y Salazar-Vázquez; Vito S Hernández; Nayeli Garibay-Nieto; José Manuel Fragoso; Galileo Escobedo Journal: Clin Exp Med Date: 2015-04-18 Impact factor: 3.984
Authors: L Parrillo; V Costa; G A Raciti; M Longo; R Spinelli; R Esposito; C Nigro; V Vastolo; A Desiderio; F Zatterale; A Ciccodicola; P Formisano; C Miele; F Beguinot Journal: Int J Obes (Lond) Date: 2016-03-16 Impact factor: 5.095
Authors: Nahum Calvo; Raúl Beltrán-Debón; Esther Rodríguez-Gallego; Anna Hernández-Aguilera; Maria Guirro; Roger Mariné-Casadó; Lidón Millá; Josep M Alegret; Fàtima Sabench; Daniel del Castillo; María Vinaixa; Miguel Àngel Rodríguez; Xavier Correig; Roberto García-Álvarez; Javier A Menendez; Jordi Camps; Jorge Joven Journal: World J Gastroenterol Date: 2015-06-28 Impact factor: 5.742
Authors: Marta Riera-Borrull; Esther Rodríguez-Gallego; Anna Hernández-Aguilera; Fedra Luciano; Rosa Ras; Elisabet Cuyàs; Jordi Camps; Antonio Segura-Carretero; Javier A Menendez; Jorge Joven; Salvador Fernández-Arroyo Journal: J Am Soc Mass Spectrom Date: 2015-09-17 Impact factor: 3.109