Targeted profiling of amino acid metabolome in serum by a liquid chromatography-mass spectrometry method: application to identify potential markers for diet-induced hyperlipidemia

Abstract

To better understand the mechanism of hyperlipidemia and discover potential biomarkers, we have used targeted metabolomics to analyze eight amino acid profiles of control and hyperlipidemia rats by a liquid chromatography-mass spectrometry method. With high fat diet, the concentrations of serum of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (ApoB) were increased by 666.7%, 99.0%, 61.7% and 51.0%, whereas the concentrations of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (ApoA-I) were decreased by 46.3% and 58.9%. The concentrations of alanine, arginine, lysine, methionine, serine, tyrosine and valine in hyperlipidemia rats were significantly decreased by 21.8%, 19.72%, 26.5%, 19.6%, 48.7%, 19.8% and 24.91%, while there was no striking change in threonine. Combined with experimental results and previous literature, we inferred that alanine and serine were gradually disordered and subsequently generated abundant acetyl-CoA through pyruvate, which resulted in energy metabolism deficiency. Furthermore, Spearman correlation analysis shows that TC was negatively associated with methionine (r = −0.640, p < 0.05), suggesting that the lowered level of methionine caused by the homocysteine pathway enhances absorption and synthesis of TC. Meanwhile, the reduction of tyrosine demonstrated that rapid metabolism of cholesterol in vivo was caused by high levels of exogenous cholesterol. Furthermore, the observed ApoB and lysine changes indicated that lysine was largely incorporated into ApoB particles during the disease process. In addition, the levels of arginine, SOD and MDA reflected the behavior of oxidative stress. Finally, the metabolism fluctuation of valine demonstrated that abnormal lipid metabolism could cause abnormal glucose metabolism. In general, disordered energy metabolism, lipid metabolism, glucose metabolism and elevated oxidative stress were important characteristics of metabolic perturbations in hyperlipidemia. Herein, the discovery of biomarkers and the biological explanations mentioned above could be used to analyze the pathogenesis of hyperlipidemia through metabolic pathways, and these results could play an important role in assisting the clinical diagnosis of hyperlipidemia.