Rodríguez-Gallego E, Guirro M, Riera-Borrull M, Hernández-Aguilera A, Mariné-Casadó R, Fernández-Arroyo S, Beltrán-Debón R, Sabench F, Hernández M, del Castillo D, Menendez J A, Camps J, Ras R, Arola L, Joven J
Unitat de Recerca Biomèdica, Hospital Universitari Sant Joan, Institut d'Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili, Reus, Spain.
Servei de Cirurgia General i de l'Aparell Digestiu, Hospital Universitari de Sant Joan de Reus, Universitat Rovira i Virgili, Reus, Spain.
Int J Obes (Lond). 2015 Feb;39(2):279-87. doi: 10.1038/ijo.2014.53. Epub 2014 Mar 28.
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.
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.
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.
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.
肥胖严重影响人类健康，与之相关的非酒精性脂肪性肝病（NAFLD）具有较高的发病率和死亡率。快速且无创的检测方法可显著改善临床护理。
我们采用液相和气相色谱-四极杆飞行时间质谱（LC/GC-QTOF-MS）分析，以非靶向代谢组学方法对接受减肥手术的病态肥胖患者的血浆进行分析，全面测量代谢物水平。基于这些发现，我们开发了一种方法（GC-QTOF-MS）用于准确量化血浆α-酮戊二酸，以探索其作为检测NAFLD新型生物标志物的潜力。
观察到非酒精性脂肪性肝病患者与非患者之间存在血浆生化差异，表明肝细胞内脂质积累会降低β-氧化能量产生、肝功能下降并改变葡萄糖代谢。血浆分析结果提示了将脂质和葡萄糖紊乱与α-酮戊二酸联系起来的病理生理学见解。与瘦对照组相比，肥胖患者血浆α-酮戊二酸水平显著升高。在肥胖患者中，该代谢物的测量可区分有无非酒精性脂肪性肝病。肝脏数据与血浆数据一致。评估了临床效用，结果显示血浆α-酮戊二酸在患者（n = 230）中是一种中等至良好的生物标志物。常规应用中使用的其他常见实验室肝功能检查与之相比并无优势。
在肥胖患者中，血浆α-酮戊二酸作为非酒精性脂肪性肝病的替代生物标志物优于常见肝功能检查。测量该生物标志物可能有助于寻找治疗方法，减少肝活检需求，并可用于评估疾病进展。
