Pérez-Díaz Armando J, Ros-Madrid Inmaculada, Martínez-Sánchez María A, Rico-Chazarra Sara, Oliva-Bolarín Alba, Balaguer-Román Andrés, Fernández-Ruiz Virginia E, Martínez Carlos M, Yuste José E, Ferrer-Gómez Mercedes, Llamoza-Torres Camilo J, Frutos María D, Núñez-Sánchez María Á, Ramos-Molina Bruno
Department of Science, University "ROMA TRE", Rome, Italy.
Obesity, Diabetes and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB), Murcia, Spain.
J Physiol Biochem. 2025 May 8. doi: 10.1007/s13105-025-01086-7.
Deregulation of amino acid (AA) metabolism has been reported in several pathological conditions, including metabolic diseases (e.g., obesity and diabetes), cardiovascular diseases, and cancer. However, the role of alterations in AA levels in chronic liver disorders such as metabolic dysfunction-associated steatotic liver disease (MASLD) remains largely unexplored. In this study we aimed to evaluate the hepatic AA composition in patients with different stages of MASLD, and their relationship with MASLD-related risk factors. A case-control study was conducted in 40 patients with obesity undergoing bariatric surgery at Virgen de la Arrixaca University Hospital (Murcia, Spain), where MASLD diagnosis was confirmed by histological analysis of liver biopsies, and hepatic AA levels were measured using ultra-performance liquid chromatography high-resolution time-of-flight mass spectrometry. Our results revealed that the hepatic AA profile was significantly altered in patients with MASLD. More specifically, comparison between MASLD patients revealed a significant increase in hepatic levels of arginine, glycine and cystine in MASH samples compared to steatotic livers. In addition, hepatic concentrations of arginine, lysine and cystine positively correlated with histopathological diagnosis and other MASLD-related parameters, including transaminases and CK-18 levels. These findings suggest that alterations in certain hepatic AA levels such as arginine, lysine, glycine and cystine in MASLD patients could have translational relevance in understanding the onset of this disease.
氨基酸（AA）代谢失调在多种病理状况中均有报道，包括代谢性疾病（如肥胖症和糖尿病）、心血管疾病以及癌症。然而，在诸如代谢功能障碍相关脂肪性肝病（MASLD）等慢性肝脏疾病中，AA水平变化的作用在很大程度上仍未得到充分探索。在本研究中，我们旨在评估不同阶段MASLD患者的肝脏AA组成，以及它们与MASLD相关危险因素的关系。在西班牙穆尔西亚的阿瑞萨卡圣母大学医院对40例接受减肥手术的肥胖患者进行了一项病例对照研究，通过肝脏活检的组织学分析确诊MASLD，并使用超高效液相色谱高分辨率飞行时间质谱法测量肝脏AA水平。我们的结果显示，MASLD患者的肝脏AA谱有显著改变。更具体地说，MASLD患者之间的比较显示，与脂肪性肝脏相比，MASH样本中肝脏精氨酸、甘氨酸和胱氨酸水平显著升高。此外，精氨酸、赖氨酸和胱氨酸的肝脏浓度与组织病理学诊断以及其他MASLD相关参数（包括转氨酶和CK-18水平）呈正相关。这些发现表明，MASLD患者肝脏中某些AA水平（如精氨酸、赖氨酸、甘氨酸和胱氨酸）的变化可能与理解该疾病的发病机制具有转化相关性。
