Metabolomic Biomarkers for Obesity in Humans: A Short ReviewRauschert S. · Uhl O. · Koletzko B. · Hellmuth C.
Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children's Hospital, Ludwig Maximilian University of Munich, Munich, Germany
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Background: The prevalence and incidence of obesity have become a major public health problem during the last decades, but the underlying biochemical and metabolic processes are not fully understood. Metabolomics, the science of small molecules of the metabolism, is helping to unravel these mechanisms via the identification of markers related to obesity. These biomarkers are used to prevent diseases in later life or for the early diagnosis of diseases. This review focuses on articles dealing with biomarkers for obesity. Key Messages: Branched-chain amino acids (BCAA), nonesterified fatty acids, organic acids, acylcarnitines, and phospholipids were identified as potential biomarkers for obesity. This indicates a relation between elevated BCAA, and other amino acids, and the obese state. Furthermore, deregulation of β-oxidation is associated with the development of obesity. The results have several limitations, including the differing ages of the subjects in the studies, the fact that all of the studies had a case-control design and therefore no causal explanatory power, and that most looked for similar metabolites and reported almost equal results. Conclusion: The strength of this review is that it gives a comprehensive overview of the current status of the knowledge on metabolomics biomarkers for obesity, but further research is needed because the methods used in the studies to date are very homogenous, e.g. most used a targeted approach and therefore analyzed almost the same group of metabolites. Moreover, prospective studies are lacking since all of the studies are either case-control or cross-sectional studies.
© 2014 S. Karger AG, Basel
- Ebbeling CB, Pawlak DB, Ludwig DS: Childhood obesity: public-health crisis, common sense cure. Lancet 2002;360:473-482.
- James PT, Rigby N, Leach R: The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil 2004;11:3-8.
- Guilherme A, Virbasius JV, Puri V, Czech MP: Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 2008;9:367-377.
- Sowers JR: Obesity as a cardiovascular risk factor. Am J Med 2003;115(suppl 8A):37S-41S.
- Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Fernando C: Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement - executive summary. Crit Pathw Cardiol 2005;4:198-203.
- Koletzko B, von Kries R, Closa R, Escribano J, Scaglioni S, Giovannini M, Beyer J, Demmelmair H, Anton B, Gruszfeld D, Dobrzanska A, Sengier A, Langhendries JP, Rolland Cachera MF, Grote V: Can infant feeding choices modulate later obesity risk? Am J Clin Nutr 2009;89:1502S-1508S.
- Weinberger KM: Metabolomics in diagnosing metabolic diseases (in German). Ther Umsch 2008;65:487-491.
- Griffiths WJ, Koal T, Wang Y, Kohl M, Enot DP, Deigner HP: Targeted metabolomics for biomarker discovery. Angewandte Chemie Int Ed Engl 2010;49:5426-5445.
- Oberbach A, Bluher M, Wirth H, Till H, Kovacs P, Kullnick Y, Schlichting N, Tomm JM, Rolle-Kampczyk U, Murugaiyan J, Binder H, Dietrich A, von Bergen M: Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes. J Proteome Res 2011;10:4769-4788.
- Mihalik SJ, Goodpaster BH, Kelley DE, Chace DH, Vockley J, Toledo FG, DeLany JP: Increased levels of plasma acylcarnitines in obesity and type 2 diabetes and identification of a marker of glucolipotoxicity. Obesity (Silver Spring) 2010;18:1695-1700.
- Wahl S, Yu Z, Kleber M, Singmann P, Holzapfel C, He Y, Mittelstrass K, Polonikov A, Prehn C, Romisch-Margl W, Adamski J, Suhre K, Grallert H, Illig T, Wang-Sattler R, Reinehr T: Childhood obesity is associated with changes in the serum metabolite profile. Obes Facts 2012;5:660-670.
- Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP: A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009;9:311-326.
- Moore SC, Matthews CE, Sampson JN, Stolzenberg-Solomon RZ, Zheng W, Cai Q, Tan YT, Chow WH, Ji BT, Liu DK, Xiao Q, Boca SM, Leitzmann MF, Yang G, Xiang YB, Sinha R, Shu XO, Cross AJ: Human metabolic correlates of body mass index. Metabolomics 2014;10:259-269.
- Kim JY, Park JY, Kim OY, Ham BM, Kim HJ, Kwon DY, Jang Y, Lee JH: Metabolic profiling of plasma in overweight/obese and lean men using ultra performance liquid chromatography and Q-TOF mass spectrometry (UPLC-Q-TOF MS). J Proteome Res 2010;9:4368-4375.
- Houten SM, Wanders RJ: A general introduction to the biochemistry of mitochondrial fatty acid beta-oxidation. J Inherit Metab Dis 2010;33:469-477.
- Samuel VT, Petersen KF, Shulman GI: Lipid-induced insulin resistance: unravelling the mechanism. Lancet 2010;375:2267-2277.
- Platell C, Kong SE, McCauley R, Hall JC: Branched-chain amino acids. J Gastroenterol Hepatol 2000;15:706-717.
- Paul HS, Adibi SA: Effect of carnitine on branched-chain amino acid oxidation by liver and skeletal muscle. Am J Physiol 1978;234:E494-E499.
- Zeng M, Liang Y, Li H, Wang M, Wang B, Chen X, Zhou N, Cao D, Wu J: Plasma metabolic fingerprinting of childhood obesity by GC/MS in conjunction with multivariate statistical analysis. J Pharm Biomed Anal 2010;52:265-272.
- McCormack SE, Shaham O, McCarthy MA, Deik AA, Wang TJ, Gerszten RE, Clish CB, Mootha VK, Grinspoon SK, Fleischman A: Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatr Obes 2013;8:52-61.
- Mihalik SJ, Michaliszyn SF, de las Heras J, Bacha F, Lee S, Chace DH, DeJesus VR, Vockley J, Arslanian SA: Metabolomic profiling of fatty acid and amino acid metabolism in youth with obesity and type 2 diabetes: evidence for enhanced mitochondrial oxidation. Diabetes Care 2012;35:605-611.
- Cheng Y, Meng Q, Wang C, Li H, Huang Z, Chen S, Xiao F, Guo F: Leucine deprivation decreases fat mass by stimulation of lipolysis in white adipose tissue and upregulation of uncoupling protein 1 (UPC1) in brown adipose tissue. Diabetes 2010;59:17-25.
- Goichon A, Chan P, Lecleire S, Coquard A, Cailleux AF, Walrand S, Lerebours E, Vaudry D, Dechelotte P, Coeffier M: An enteral leucine supply modulates human duodenal mucosal proteome and decreases the expression of enzymes involved in fatty acid beta-oxidation. J Proteomics 2013;78:535-544.
- Suryawan A, Davis TA: Regulation of protein synthesis by amino acids in muscle of neonates. Front Biosci 2011;16:1445-1460.
- Melnik BC: Excessive leucine-mTORC1-signalling of cow milk-based infant formula: the missing link to understand early childhood obesity. J Obes 2012;2012:197653.
- Adams SH: Emerging perspectives on essential amino acid metabolism in obesity and the insulin-resistant state. Adv Nutr 2011;2:445-456.
- Xu F, Tavintharan S, Sum CF, Woon K, Lim SC, Ong CN: Metabolic signature shift in type 2 diabetes mellitus revealed by mass spectrometry-based metabolomics. J Clin Endocrinol Metab 2013;98:E1060-E1065.
- Floegel A, Stefan N, Yu Z, Muhlenbruch K, Drogan D, Joost HG, Fritsche A, Haring HU, Hrabe de Angelis M, Peters A, Roden M, Prehn C, Wang-Sattler R, Illig T, Schulze MB, Adamski J, Boeing H, Pischon T: Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes 2013;62:639-648.
- Würtz P, Soininen P, Kangas AJ, Ronnemaa T, Lehtimaki T, Kahonen M, Viikari JS, Raitakari OT, Ala-Korpela M: Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults. Diabetes Care 2013;36:648-655.
- Glaser C, Demmelmair H, Koletzko B: High-throughput analysis of fatty acid composition of plasma glycerophospholipids. J Lipid Res 2010;51:216-221.
- Uhl O, Glaser C, Demmelmair H, Koletzko B: Reversed phase LC/MS/MS method for targeted quantification of glycerophospholipid molecular species in plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2011;879:3556-3564.
- Hellmuth C, Demmelmair H, Schmitt I, Peissner W, Bluher M, Koletzko B: Association between plasma nonesterified fatty acids species and adipose tissue fatty acid composition. PLoS One 2013;8:e74927.
- Hellmuth C, Uhl O, Segura-Moreno M, Demmelmair H, Koletzko B: Determination of acylglycerols from biological samples with chromatography-based methods. J Sep Sci 2011;34:3470-3483.
- Glaser C, Demmelmair H, Koletzko B: High-throughput analysis of total plasma fatty acid composition with direct in situ transesterification. PLoS One 2010;5:e12045.
- Okada T, Furuhashi N, Kuromori Y, Miyashita M, Iwata F, Harada K: Plasma palmitoleic acid content and obesity in children. Am J Clin Nutr 2005;82:747-750.
- Caron-Jobin M, Mauvoisin D, Michaud A, Veilleux A, Noel S, Fortier MP, Julien P, Tchernof A, Mounier C: Stearic acid content of abdominal adipose tissues in obese women. Nutr Diabetes 2012;2:e23.
- Garaulet M, Hernandez-Morante JJ, Tebar FJ, Zamora S: Relation between degree of obesity and site-specific adipose tissue fatty acid composition in a Mediterranean population. Nutrition 2011;27:170-176.
- Warensjö E, Ohrvall M, Vessby B: Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women. Nutr Metab Cardiovasc Dis 2006;16:128-136.
- Karlsson M, Marild S, Brandberg J, Lonn L, Friberg P, Strandvik B: Serum phospholipid fatty acids, adipose tissue, and metabolic markers in obese adolescents. Obesity (Silver Spring) 2006;14:1931-1939.
- Karpe F, Dickmann JR, Frayn KN: Fatty acids, obesity, and insulin resistance: time for a reevaluation. Diabetes 2011;60:2441-2449.
- Pietiläinen KH, Sysi-Aho M, Rissanen A, Seppanen-Laakso T, Yki-Jarvinen H, Kaprio J, Oresic M: Acquired obesity is associated with changes in the serum lipidomic profile independent of genetic effects - a monozygotic twin study. PLoS One 2007;2:e218.
- Newgard CB: Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab 2012;15:606-614.
- Goh VH, Tain CF, Tong TY, Mok HP, Wong MT: Are BMI and other anthropometric measures appropriate as indices for obesity? A study in an Asian population. J Lipid Res 2004;45:1892-1898.
- Camhi SM, Bray GA, Bouchard C, Greenway FL, Johnson WD, Newton RL, Ravussin E, Ryan DH, Smith SR, Katzmarzyk PT: The relationship of waist circumference and BMI to visceral, subcutaneous, and total body fat: sex and race differences. Obesity (Silver Spring) 2011;19:402-408.
- Netzer M, Kugler KG, Muller LA, Weinberger KM, Graber A, Baumgartner C, Dehmer M: A network-based feature selection approach to identify metabolic signatures in disease. J Theor Biol 2012;310:216-222.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.