Metabolic Profiling of Plasma in Overweight/Obese and Lean Men using Ultra Performance Liquid Chromatography and Q-TOF Mass Spectrometry (UPLC-Q-TOF MS) Ji Young Kim, †,‡,§ Ju Yeon Park, ‡,§,| Oh Yoen Kim, †,‡ Bo Mi Ham, ‡ Hyun-Jin Kim, ⊥ Dae Young Kwon, ⊥ Yangsoo Jang, †,#,¶ and Jong Ho Lee* ,†,‡,| Yonsei University Research Institute of Science for Aging, Yonsei University, Seoul, Korea, Laboratory of Clinical Nutrigenetics/Nutrigenomics, Yonsei University, Seoul, Korea, Department of Food and Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University, Seoul, Korea, Emerging Innovative Technology Research Division, Korean Food Research Institutes, Korea, Cardiology Division, Yonsei University College of Medicine, Yonsei Cardiovascular Center, Seoul, Korea, and Cardiovascular Genome Center, Yonsei Medical Institute, Yonsei University, Seoul, Korea Received February 3, 2010 Obesity is currently epidemic in many countries worldwide and is strongly related to diabetes and cardiovascular disease. This study investigated the differences in metabolomic profiling between overweight/obese and normal-weight men. Overweight/obese (n ) 30) and age-matched, normal-weight men (n ) 30) were included. Anthropometric parameters, conventional metabolites, and biomarkers were measured. Metabolomic profiling was analyzed with UPLC-Q-TOF MS. Overweight/obese men showed higher levels of HOMA-IR, triglycerides, total cholesterol, and LDL-cholesterol, and lower levels of HDL-cholesterol and adiponectin than lean men. Overweight/obese men showed higher proportion of stearic acid and lower proportion of oleic acid in serum phospholipids. Additionally, overweight/ obese individuals showed higher fat intake and lower ratio of polyunsaturated fatty acids to saturated fatty acids. We identified three lyso-phosphatidylcholine (lysoPC) as potential plasma markers and confirmed eight known metabolites for overweight/obesity men. Especially, overweight/obese subjects showed higher levels of lysoPC C14:0 and lysoPC C18:0 and lower levels of lysoPC C18:1 than lean subjects. Results confirmed abnormal metabolism of two branched-chain amino acids, two aromatic amino acids, and fatty acid synthesis and oxidation in overweight/obese men. Additionally, the amount of dietary saturated fat may influence the proportion of saturated fatty acids in serum phospholipids and the degree of saturation of the constituent acyl group of plasma lysoPC. Keywords: metabolic profiles • obesity • UPLC-Q-TOF MS • lyso-phosphatidylcholine • saturated fat Introduction Obesity has reached epidemic proportions in many countries around the world and is strongly related to diabetes and cardiovascular disease. 1 Whereas many comparisons of obese and lean subjects exist in the literature, they often focus on a small group of experimental variables. Obesity cosegregates with metabolic abnormalities, including dyslipidemia and glucose intolerance; 2 however, obesity-induced perturbations in metabolism have not been clearly established. Complex etiologies interacting with environmental factors highlight the need to understand how metabolite profiles are altered in this state. Metabolomics is an important technological discipline that focuses on the measurement of the relative concentrations of endogenous small molecules in biofluids, which characterizes changes in metabolism 3 and helps unravel the metabolic state of biological systems. 4 Metabolomics involves establishing relationships between phenotype and metabolism, which are key aspects of biological function. These approaches have been applied to identify serum/plasma metabolic markers involved in obesity, 5-7 diabetes, 8-10 and coronary artery disease 11 through animal models or in humans. A new method of ultraperformance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF MS) was developed for sample analysis to obtain better quality and throughput for the analysis of complex mixtures. This sensitive, high-resolution system can acquire multiparametric metabolite profiles from biofluids rapidly and effectively as a powerful * To whom correspondence should be addressed. Jong Ho Lee, PhD Department of Food & Nutrition, College of Human Ecology, Yonsei University, 134 Shinchon-Dong, Sudaemun-Gu, Seoul, 120-749, Korea. Fax: +82-2-364-9605. Tel: +82-2-2123-3122. E-mail: jhleeb@yonsei.ac.kr. † Yonsei University Research Institute of Science for Aging, Yonsei University. ‡ Laboratory of Clinical Nutrigenetics/Nutrigenomics, Yonsei University. § These authors contributed equally to this work. | Department of Food & Nutrition, Brain Korea 21 Project, College of Human Ecology, Yonsei University. ⊥ Korean Food Research Institutes. # Yonsei Cardiovascular Center. ¶ Yonsei Medical Institute, Yonsei University. 4368 Journal of Proteome Research 2010, 9, 4368–4375 10.1021/pr100101p  2010 American Chemical Society Published on Web 06/18/2010