Understanding 'Global' Systems Biology: Metabonomics and the Continuum of Metabolism

Nicholson, Jeremy K.; Wilson, Ian D.

doi:10.1038/nrd1157

Cited by 1,020 publications

(725 citation statements)

References 49 publications

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“…[4][5][6][7] Metabonomics addresses complete biological systems by studying metabolic profiles, mainly in biofluids, which gives a window on whole systems biochemistry and thus promises to provide crucial information on drug toxicity, disease processes and gene function. 8 However, in order to be confident of perturbed metabolic profiles in such cases, it is necessary to characterize the boundaries of metabolic 'normality'. For instance, there is anecdotal evidence that an estimated 3-5% of experimental animals are not healthy prior to inclusion in toxicological studies and as a result show anomalous responses to toxins.…”

Section: Introductionmentioning

confidence: 99%

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

et al. 2004

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Strategies such as genomics, proteomics and metabonomics are being applied with increasing frequency in the pharmaceutical industry. For each of these approaches, toxicological response can be measured by terms of deviation from control or baseline status. However, in order to accurately define drug-induced response, it is necessary to characterize the normal degree of physiological variation in the absence of stimuli. Here, 1 H NMR spectroscopic-based analyses of the metabolic composition of urine in experimental animals under various normal physiological conditions are reviewed. In particular, the effects of inter-animal and diurnal variation, gender, age, diet, species, strain, hormonal status and stress on the biochemical composition of urine are explored. Pattern recognition methods facilitate the comparison of urine NMR spectra over a given time-course, enabling the establishment of changes in profile and highlighting the dynamic metabolic status of an organism. Thus metabonomic approaches based on information-rich spectroscopic data sets can be used to evaluate normal physiological variation and for investigation of drug safety issues.

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Section: Introductionmentioning

confidence: 99%

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

et al. 2004

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“…Progress in gene expression profiling technologies and genome functional annotations can help improve knowledge of NAFLD-associated markers. Functional genomic tools, including transcriptomics and metabonomics, a technology designed to quantify metabolites in biological samples [6], generate high-density data sets underlying disease-related mechanisms at either end of the regulation of gene expression. Alterations in transcription regulation of hepatic carbohydrate and lipogenic pathways have a central role in mechanisms contributing to insulin resistance and NAFLD [7,8].…”

Section: Introductionmentioning

confidence: 99%

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

et al. 2007

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Aims/hypothesis Complex changes in gene expression are associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD) promoted by feeding a high-fat diet (HFD). We used functional genomic technologies to document molecular mechanisms associated with dietinduced NAFLD. Materials and Methods Male 129S6 mice were fed a diet containing 40% fat (high-fat diet, HFD) for 15 weeks. Glucose tolerance, in vivo insulin secretion, plasma lipid profile and adiposity were determined. Plasma metabonomics and liver transcriptomics were used to identify changes in gene expression associated with HFD-induced NAFLD.Results In HFD-fed mice, NAFLD and impaired glucose and lipid homeostasis were associated with increased hepatic transcription of genes involved in fatty acid uptake, intracellular transport, modification and elongation, whilst genes involved in beta-oxidation and lipoprotein secretion were, paradoxically, also upregulated. NAFLD developed despite strong and sustained downregulation of transcription of the gene encoding stearoyl-coenzyme A desaturase 1 (Scd1) and uncoordinated regulation of transcription of Scd1 and the gene encoding sterol regulatory element binding factor 1c (Srebf1c) transcription. Inflammatory mechanisms appeared to be stimulated by HFD. Conclusions/interpretation Our results provide an accurate representation of subtle changes in metabolic and gene expression regulation underlying disease-promoting and compensatory mechanisms, collectively contributing to dietinduced insulin resistance and NAFLD. They suggest that proposed models of NAFLD pathogenesis can be enriched with novel diet-reactive genes and disease mechanisms.

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“…One area of considerable interest in the field of metabolomics is to detect potential biomarkers associated with diseases, and metabolic profiling could provide global changes of endogenous metabolites of patients. 9 It involves the comprehensive profiling of the full complement of low molecular weight compounds in a biological system. By applying advanced analytical and statistical tools, the ''metabolome'' is mined for biomarkers that are associated with the state of HCC.…”

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confidence: 99%

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

2013

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Hepatocellular carcinoma (HCC) is the commonest primary hepatic malignancy and the third most common cause of cancer-related death worldwide. Incidence remains highest in the developing world and is steadily increasing across the developed world. Current diagnostic modalities, of ultrasound and a-fetoprotein, are expensive and lack sensitivity in tumor detection. Because of its asymptomatic nature, HCC is usually diagnosed at late and advanced stages, for which there are no effective therapies. Thus, biomarkers for early detection and molecular targets for treating HCC are urgently needed. Emerging highthroughput metabolomics technologies have been widely applied, aiming at the discovery of candidate biomarkers for cancer staging, prediction of recurrence and prognosis, and treatment selection. Metabolic profiles, which are affected by many physiological and pathological processes, may provide further insight into the metabolic consequences of this severe liver disease. Small-molecule metabolites have an important role in biological systems and represent attractive candidates to understand HCC phenotypes. The power of metabolomics allows an unparalleled opportunity to query the molecular mechanisms of HCC. This technique-driven review aims to demystify the metabolomics pathway, while also illustrating the potential of this technique, with recent examples of its application in

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Understanding 'Global' Systems Biology: Metabonomics and the Continuum of Metabolism

Cited by 1,020 publications

References 49 publications

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition

Subtle metabolic and liver gene transcriptional changes underlie diet-induced fatty liver susceptibility in insulin-resistant mice

Power of metabolomics in diagnosis and biomarker discovery of hepatocellular carcinoma

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