Monitoring Metabolic Disease by Proton NMR of Urine

Nicholson, Jeremy K.; Sadler, P J; Bales, JohnR.; Juul, S M; Macleod, Andrew; Sönksen, P. H.

doi:10.1016/s0140-6736(84)92656-4

Cited by 43 publications

(24 citation statements)

References 6 publications

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“…We have shown that high-resolution 'H NMR spectroscopy can be used to analyze untreated biological samples such as urine and plasma. Many important intermediary metabolites can be detected by 'H NMR, and quantitative information can be obtained which compares well with that from conventional analytical techniques (1)(2)(3)(4)(5).…”

Section: Introductionmentioning

confidence: 80%

¹H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine

Bales

Bell

Nicholson

et al. 1986

Magnetic Resonance in Med

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High-resolution 1H NMR spectroscopy has been applied to a study of urine from five normal human subjects during a 48-h period of fasting and for 22 h thereafter. The excretion rates of all three ketone bodies (acetoacetate, 3-D-hydroxybutyrate, and acetone), acetylcarnitine, creatinine, and sarcosine during this period were measured. Parallel increases in the excretion of the ketone bodies and acetylcarnitine were observed during fasting with little change in the output of creatinine and sarcosine.

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Section: Introductionmentioning

confidence: 80%

¹H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine

Bales

Bell

Nicholson

et al. 1986

Magnetic Resonance in Med

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“…2B, showing contributions of a wide range of low-molecularmass metabolites (Ͻ1 kDa) from both mammalian metabolism and associated gut-microbial systems (24,25). The urinary 1 H NMR spectrum of this 129S6 mouse on HFD is dominated by microbiota-derived methylamines: dimethylamine, trimethylamine (TMA), and trimethylamine-N-oxide (TMAO).…”

Section: Metabolic Profiling By 1 H Nmr Spectroscopy At 4 Months Aftementioning

confidence: 99%

Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice

Dumas¹,

Barton²,

Toye

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

973

744

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Here, we study the intricate relationship between gut microbiota and host cometabolic phenotypes associated with dietary-induced impaired glucose homeostasis and nonalcoholic fatty liver disease (NAFLD) in a mouse strain (129S6) known to be susceptible to these disease traits, using plasma and urine metabotyping, achieved by 1 H NMR spectroscopy. Multivariate statistical modeling of the spectra shows that the genetic predisposition of the 129S6 mouse to impaired glucose homeostasis and NAFLD is associated with disruptions of choline metabolism, i.e., low circulating levels of plasma phosphatidylcholine and high urinary excretion of methylamines (dimethylamine, trimethylamine, and trimethylamine-Noxide), coprocessed by symbiotic gut microbiota and mammalian enzyme systems. Conversion of choline into methylamines by microbiota in strain 129S6 on a high-fat diet reduces the bioavailability of choline and mimics the effect of choline-deficient diets, causing NAFLD. These data also indicate that gut microbiota may play an active role in the development of insulin resistance.metabonomics ͉ NMR ͉ nonalcoholic fatty liver disease ͉ nutritional genomics ͉ metabolic syndrome H ighly complex animals such as mammals can be considered as ''superorganisms'' with a karyome, a chondriome, and a microbiome (1), resulting from a coevolutionary symbiotic ecosystem of diverse intestinal microbiota interacting metabolically with the host (2). Recent molecular analyses of human microbiota 16s ribosomal DNA sequences revealed a majority of uncultivated or unknown species with a strong degree of interindividual diversity (3, 4). Also, some of the molecular foundations of beneficial symbiotic host-bacteria relationships in the gut were revealed by colonization of germ-free mice with known microbes and by comparisons of the genomes of members of the intestinal microbiota (5). For instance, Bacteroides thetaiotaomicron, a dominant member of normal distal intestinal microbiota, hydrolyzes otherwise indigestible dietary polysaccharides, thus supplying the host with 10-15% of calorific requirement (6). Gut Lactobacillus spp. are also responsible for a significant proportion of bile acid deconjugation, a process that efficiently reduces lipid absorption in the gut (7). Such symbiotic relationships are the result of coevolution and operate at the genome, proteome, and metabolome levels (6,8).Insulin resistance (IR) is central to a cluster of frequent and increasingly prevalent pathologies, including type 2 diabetes mellitus, central obesity, hypertension hepatic steatosis, and dyslipidemia (9). IR contributes to major causes of morbidity and mortality worldwide (10). Epidemiological and genetic studies in human and animal models have demonstrated the importance of both genetic and environmental factors in the etiology of IR (9): Dietary variation and intervention, in particular, have a strong influence on the development of IR. Nonalcoholic fatty liver disease (NAFLD), is the most frequent liver condition associated with IR (11). It is associa...

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“…Various studies have demonstrated the application of metabonomic/metabolomic analysis utilising 1 H NMR spectroscopy in a wide range of biofluids, particularly in blood (for example Nicholson et al, 1983Nicholson et al, , 1995Lenz et al, 2003) and urine (for example Yoshikawa et al, 1982;Nicholson et al, 1984;Keun et al, 2002;Daykin et al, 2005). Such an approach to biofluid metabolic profiling and statistical pattern recognition requires no prior knowledge of potential compounds of interest, metabolites being identified based on their correlated variation between treatment groups.…”

Section: Introductionmentioning

confidence: 99%

Study of metabolite composition of eccrine sweat from healthy male and female human subjects by 1H NMR spectroscopy

et al. 2006

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The aim of the study was to evaluate metabolite variability in human eccrine sweat using a metabonomics based approach. Eccrine sweat is a dilute electrolyte solution whose primary function is to control body temperature via evaporative cooling. Although the composition of sweat is primarily water, previous studies have shown that a diverse array of organic and inorganic compounds are also present. Human eccrine sweat samples from 30 female and 30 male subjects were analysed using highresolution 1 H nuclear magnetic resonance (NMR) spectroscopy in conjunction with statistical pattern recognition. High-resolution 1 H NMR spectroscopy produced spectra of the sweat samples that readily identified and quantified many different metabolites. The major metabolite classes found to be present were lactate, amino acids and lipids, with lactate being by far the most dominant metabolite found in all samples. Principal Components Analysis, Principal Components-Discriminant Analysis and Partial Least Squares-Discriminant Analysis of the eccrine sweat samples, revealed no significant differences in metabolite composition and concentration between female and male subjects. Also, the variation between subjects did not appear to be correlated with any other clinical information provided by the subjects. Overall, the spectra data set demonstrates the large physiological variability in terms of number of metabolites present and concentrations between subjects i.e. human eccrine sweat samples exhibit a high degree of inter-individual variability.

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Monitoring Metabolic Disease by Proton NMR of Urine

Cited by 43 publications

References 6 publications

¹H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine

¹H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine

Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice

Study of metabolite composition of eccrine sweat from healthy male and female human subjects by 1H NMR spectroscopy

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Monitoring Metabolic Disease by Proton NMR of Urine

Cited by 43 publications

References 6 publications

1H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine

1H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine

Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice

Study of metabolite composition of eccrine sweat from healthy male and female human subjects by 1H NMR spectroscopy

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¹H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine

¹H NMR studies of urine during fasting: Excretion of ketone bodies and acetylcarnitine