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Metabolomics

Identification of Disease- and Nutrient-Related Metabolic Fingerprints in Osteoarthritic Guinea Pigs

Robert-Jan A. N. Lamers², Jeroen DeGroot^*, Elly J. Spies-Faber, Renger H. Jellema, Virginia B. Kraus, Nicole Verzijl^*, Johan M. TeKoppele^*, Gerwin K. Spijksma, Jack T.W.E. Vogels, Jan van der Greef and Joop H. J. van Nesselrooij

TNO Netherlands Organization for Applied Scientific Research, Nutrition and Food Research and Pharma, 3700 AJ Zeist, The Netherlands; ^* TNO Prevention and Health, Gaubius Laboratory, 2301 CE Leiden, The Netherlands; and Duke University Medical Center, Department of Medicine, Division of Rheumatology, Allergy and Clinical Immunology, Durham, NC 27710

²To whom correspondence should be addressed. E-mail: r.lamers{at}voeding.tno.nl.

Osteoarthritis (OA), one of the most common diseases among the elderly, is characterized by the progressive destruction of joint tissues. Its etiology is largely unclear and no effective disease-modifying treatment is currently available. Metabolic fingerprinting provides a novel tool for the identification of biomarkers. A metabolic fingerprint consists of a typical combination of metabolites in a biological fluid and is identified by a combination of ¹H NMR spectroscopy and multivariate data analysis (MVDA). The current feasibility study was aimed at identifying a metabolic fingerprint for OA and applying this in a nutritional intervention study. Urine samples were collected from osteoarthritic male Hartley guinea pigs (n = 44) at 10 and 12 mo of age, treated from 4 mo onward with variable vitamin C doses (2.5–3, 30 and 150 mg/d) and from healthy male Strain 13 guinea pigs (n = 8) at 12 mo of age, treated with 30 mg vitamin C/d. NMR measurements were performed on all urine samples. Subsequently, MVDA was carried out on the data obtained using NMR. An NMR fingerprint was identified that reflected the osteoarthritic changes in guinea pigs. The metabolites that comprised the fingerprint indicate that energy and purine metabolism are of major importance in OA. Metabolic fingerprinting also allowed detection of differences in OA-specific metabolites induced by different dietary vitamin C intakes. This study demonstrates the feasibility of metabolic fingerprinting to identify disease-specific profiles of urinary metabolites. NMR fingerprinting is a promising means of identifying new disease markers and of gaining fresh insights into the pathophysiology of disease.

KEY WORDS: • metabolic fingerprinting • ¹H NMR spectroscopy • multivariate data analysis • osteoarthritis • vitamin C

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