Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.
Free Radic Res. 2023 Dec;57(3):195-207. doi: 10.1080/10715762.2023.2226315. Epub 2023 Jun 28.
BACKGROUND/AIMS: In recent years, many metabolites specific to nonalcoholic fatty liver disease (NAFLD) have been identified thanks to the application of metabolomics techniques. This study aimed to investigate the candidate targets and potential molecular pathways involved in NAFLD in the presence of iron overload.
Male Sprague Dawley rats were fed with control or high-fat diet with or without excess iron. After 8, 16, 20 weeks of treatment, urine samples of rats were collected for metabolomics analysis using ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). Blood and liver samples were also collected.
High-fat, high-iron diet resulted in increased triglyceride accumulation and increased oxidative damage. A total of 13 metabolites and four potential pathways were identified. Compared to the control group, the intensities of adenine, cAMP, hippuric acid, kynurenic acid, xanthurenic acid, uric acid, and citric acid were significantly lower ( < 0.05) and the concentration of other metabolites was significantly higher in the high-fat diet group. In the high-fat, high-iron group, the differences in the intensities of the above metabolites were amplified.
Our findings suggest that NAFLD rats have impaired antioxidant system and liver function, lipid disorders, abnormal energy, and glucose metabolism, and that iron overload may further exacerbate these disorders.
背景/目的：近年来，代谢组学技术的应用鉴定出了许多与非酒精性脂肪性肝病（NAFLD）相关的特异性代谢物。本研究旨在探讨铁过载状态下 NAFLD 的候选靶点和潜在分子通路。
雄性 Sprague Dawley 大鼠分别给予对照或高脂饮食，同时给予或不给予过量铁。治疗 8、16、20 周后，收集大鼠尿液样本，采用超高效液相色谱/质谱联用技术（UPLC-MS）进行代谢组学分析。同时采集血样和肝样。
高脂、高铁饮食导致甘油三酯蓄积增加和氧化损伤加重。共鉴定出 13 种代谢物和 4 条潜在通路。与对照组相比，高脂饮食组腺嘌呤、cAMP、马尿酸、犬尿氨酸、黄尿酸、尿酸和柠檬酸的强度显著降低（ < 0.05），其他代谢物的浓度显著升高。在高脂、高铁组，上述代谢物的强度差异进一步放大。
本研究结果表明，NAFLD 大鼠的抗氧化系统和肝功能受损，脂质代谢、能量和葡萄糖代谢异常，铁过载可能进一步加重这些异常。
