A Metabolomics Approach from Metabolic Syndrome to Atherosclerosis

• Main Authors: Chun-Feng Huang, 黃駿豐
• Other Authors: 洪傳岳
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/77344100719002400737

博士 === 臺北醫學大學 === 臨床醫學研究所 === 101 === The metabolic syndrome, also termed the insulin resistance syndrome, is a multiplex disorder and puts patients on the road to type 2 diabetes and atherosclerotic cardiovascular diseases. However, a surrogate biomarker in plasma or urine in fully reflecting features of metabolic syndrome has not been explored. The aim of this study is to find potential biomarkers for metabolic syndrome through metabolomics approach. Urine metabolomics has potential utility in metabolic profiling because urine metabolites analysis reflects global outflux of metabolic change. Accordingly, This study randomly selected subjects with parameters of metabolic syndrome (overweight, dyslipidemia, hypertension or impaired glucose tolerance) and chose Sprague–Dawley rats fed with high-fructose and high-lipid diet to mimic metabolic syndrome. We took a metabolomics approach to analyze the metabolites of urine by high-performance liquid chromatography-time of flight mass spectrometry and elicit potential biomarkers to picture road from metabolic syndrome to atherosclerosis. Moreover, among the analyzed metabolites, this study also found that urinary nicotinuric acid level could reflect the pathologic mechanism of metabolic syndrome and positively correlated with body mass index, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triacylglycerol and high sensitivity C-reactive protein, but negatively correlated with high-density lipoprotein cholesterol. Finally, this study also proposed the hypothesis about the metabolic pathway to atherosclerosis via nicotinuric acid. As the end product from betaine, glycine and tryptophan, nicotinuric acid is compatible with the latest finding of atherosclerosis formation from choline via gut microbiota. Moreover, the nicotinuric acid levels in urine reveal the change of NADP+/NADPH. NADP+/NADPH are the coenzymes for oxidation-reduction reactions of fatty acid synthesis and participation in various dehydrogenase reactions of mitochondrion, cytoplasm, and endoplasmic reticulum, in the process of insulin resistance and dyslipidemia. Further interpretation of metabolic process of nicotinuric acid may provide a pathophysiologic basis for understanding the progression from metabolic syndrome to atherosclerosis.