Untargeted metabonomic analysis of non-alcoholic fatty liver disease with iron overload in rats via UPLC/MS

Background/AimsIn 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.MethodsMale 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.ResultsHigh-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 (p < 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.ConclusionOur 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.

Automated summary

In recent years, metabolomics techniques have identified many specific metabolites related to nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the candidate targets and molecular pathways involved in NAFLD when iron overload is present. Male Sprague Dawley rats were fed control or high-fat diets with or without excess iron, and metabolomics analysis was performed using UPLC-MS. The results showed that a high-fat, high-iron diet resulted in increased triglyceride accumulation and oxidative damage, and several metabolites were significantly altered in the presence of iron overload.