Metabolomics represents an emerging discipline concerned with comprehensive assessment of small molecule endogenous metabolites in biological systems and provides a powerful approach insight into the mechanisms of diseases. Type 2 diabetes (T2D), called the burden of the 21st century, is growing with an epidemic rate. However, its precise molecular mechanism has not been comprehensively explored. In this study, we applied urinary metabolomics based on the UPLC/MS integrated with pattern recognition approaches to discover differentiating metabolites, to characterize and explore metabolic pathway disruption in an experimental model for high-fat-diet induced T2D. Six differentiating urinary metabolites were found in the negative mode, and two (2-(4-hydroxy-3-methoxy-phenyl) acetaldehyde sulfate, 2-phenylethanol glucuronide) of which were identified involving the key metabolic pathways linked to pentose and glucuronate interconversions, starch, sucrose metabolism and tyrosine metabolism. Our study provides new insight into pathophysiologic mechanisms and may enhance the understanding of T2D pathogenesis.
References
[1]
Qin J, Li Y, Cai Z, Li S, Zhu J, et al. (2012) A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature 490: 55–60. doi: 10.1038/nature11450
[2]
Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, et al. (2010) Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring. Nature 467: 963–936. doi: 10.1038/nature09491
[3]
Rosengren AH, Jokubka R, Tojjar D, Granhall C, Hansson O, et al. (2010) Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes. Science 327: 217–220. doi: 10.1126/science.1176827
[4]
Zhang A, Sun H, Han Y, Yan G, Wang X (2013) Urinary metabolic biomarker and pathway study of hepatitis B virus infected patients based on UPLC-MS system. PLoS One 8: e64381. doi: 10.1371/journal.pone.0064381
[5]
Wang X, Yang B, Zhang A, Sun H, Yan G (2012) Potential drug targets on insomnia and intervention effects of Jujuboside A through metabolic pathway analysis as revealed by UPLC/ESI-SYNAPT-HDMS coupled with pattern recognition approach. J Proteomics 75: 1411–1427. doi: 10.1016/j.jprot.2011.11.011
[6]
Zhang AH, Sun H, Yan GL, Yuan Y, Han Y, et al. (2014) Metabolomics study of type 2 diabetes using ultra-performance LC-ESI/quadrupole-TOF high-definition MS coupled with pattern recognition methods. J Physiol Biochem 70: 117–128. doi: 10.1007/s13105-013-0286-z
[7]
Gjesing AP, Pedersen O (2012) ‘Omics’-driven discoveries in prevention and treatment of type 2 diabetes. Eur J Clin Invest 42: 579–588. doi: 10.1111/j.1365-2362.2012.02678.x
[8]
Zhang A, Sun H, Dou S, Sun W, Wu X, et al. (2012) Metabolomics study on the hepatoprotective effect of scoparone using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry. Analyst 138: 353–361. doi: 10.1039/c2an36382h
[9]
Zhang A, Sun H, Wang X (2013) Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma. Hepatology 57: 2072–2077. doi: 10.1002/hep.26130
[10]
Zhang A, Sun H, Wang P, Han Y, Wang X (2012) Modern analytical techniques in metabolomics analysis. Analyst 137: 293–300. doi: 10.1039/c1an15605e
[11]
Wang X, Zhang A, Han Y, Wang P, Sun H, et al. (2012) Urine metabolomics analysis for biomarker discovery and detection of jaundice syndrome in patients with liver disease. Mol Cell Proteomics 11: 370–380. doi: 10.1074/mcp.m111.016006
[12]
Jung Y, Ahn YG, Kim HK, Moon BC, Lee AY, et al. (2011) Characterization of dandelion species using 1H NMR- and GC-MS-based metabolite profiling. Analyst 136: 4222–4231. doi: 10.1039/c1an15403f
[13]
Zhang A, Sun H, Wang X (2012) Serum metabolomics as a novel diagnostic approach for disease: a systematic review. Anal Bioanal Chem 404: 1239–1245. doi: 10.1007/s00216-012-6117-1
[14]
Bain JR, Stevens RD, Wenner BR, Ilkayeva O, Muoio DM, et al. (2009) Metabolomics applied to diabetes research: moving from information to knowledge. Diabetes 58: 2429–2443. doi: 10.2337/db09-0580
[15]
Miura D, Fujimura Y, Wariishi H (2012) In situ metabolomic mass spectrometry imaging: recent advances and difficulties. J Proteomics 75: 5052–5060. doi: 10.1016/j.jprot.2012.02.011
[16]
Ugarte M, Brown M, Hollywood KA, Cooper GJ, Bishop PN, et al. (2012) Metabolomic analysis of rat serum in streptozotocin-induced diabetes and after treatment with oral triethylenetetramine (TETA). Genome Med 4: 35. doi: 10.1186/gm334
[17]
Thwe AA, Kim JK, Li X, Bok Kim Y, Romij Uddin M, et al. (2013) Metabolomic analysis and phenylpropanoid biosynthesis in hairy root culture of tartary buckwheat cultivars. PLoS One 8: e65349. doi: 10.1371/journal.pone.0065349
[18]
Wang X, Wang H, Zhang A, Lu X, Sun H, et al. (2012) Metabolomics study on the toxicity of aconite root and its processed products using ultraperformance liquid-chromatography/electrospray-ioniz？ationsynapt high-definition mass spectrometry coupled with pattern recognition approach and ingenuity pathways analysis. J Proteome Res 11: 1284–1301. doi: 10.1021/pr200963e
[19]
Gregory JF 3rd, Park Y, Lamers Y, Bandyopadhyay N, Chi YY, et al. (2013) Metabolomic analysis reveals extended metabolic consequences of marginal vitamin B-6 deficiency in healthy human subjects. PLoS One 8: e63544. doi: 10.1371/journal.pone.0063544
[20]
Zhang T, Watson DG, Wang L, Abbas M, Murdoch L, et al. (2013) Application of Holistic Liquid Chromatography-High Resolution Mass Spectrometry Based Urinary Metabolomics for Prostate Cancer Detection and Biomarker Discovery. PLoS One 8: e65880. doi: 10.1371/journal.pone.0065880
[21]
Zhang SX, Sun H, Sun WJ, Jiao GZ, Wang XJ (2010) Proteomic study of serum proteins in a type 2 diabetes mellitus rat model by Chinese traditional medicine Tianqi Jiangtang Capsule administration. J Pharm Biomed Anal 53: 1011–1014. doi: 10.1016/j.jpba.2010.06.033
[22]
Ai J, Wang N, Yang M, Du ZM, Zhang YC, et al. (2005) Development of Wistar rat model of insulin resistance. World J Gastroenterol 11: 3675–3679.
[23]
Mihalik SJ, Michaliszyn SF, de las Heras J, Bacha F, Lee S, et al. (2012) Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation. Diabetes Care 35: 605–611. doi: 10.2337/dc11-1577
[24]
Ng DP, Salim A, Liu Y, Zou L, Xu FG, et al. (2012) A metabolomic study of low estimated GFR in non-proteinuric type 2 diabetes mellitus. Diabetologia 55: 499–508. doi: 10.1007/s00125-011-2339-6
[25]
Skappak C, Regush S, Cheung PY, Adamko DJ (2013) Identifying hypoxia in a newborn piglet model using urinary NMR metabolomic profiling. PLoS One 8: e65035. doi: 10.1371/journal.pone.0065035
[26]
van Vliet E, Eixarch E, Illa M, Arbat-Plana A, González-Tendero A, et al. (2013) Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain. PLoS One 8: e64545. doi: 10.1371/journal.pone.0064545
[27]
Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, et al. (2010) Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. PLoS One 5: e15234. doi: 10.1371/journal.pone.0015234
[28]
Suhre K, Shin SY, Petersen AK, Mohney RP, Meredith D, et al. (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature 477: 54–60. doi: 10.1038/nature10354
