Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Everett, Jeremy R.

doi:10.2217/pgs.15.20

Cited by 89 publications

(63 citation statements)

References 62 publications

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“…The study of their receptors is important as they can be targets for pharmacological treatment in obesity and T2D, and genetic variations in these receptors might codetermine the responsiveness and strength of adipokine signal transduction in the target tissues. For this purpose, pharmacogenomic studies are becoming more important [129]. Genetic variants in adipokine receptors may contribute to the regulation of serum adipokine levels through a feedback mechanism of downstream components which sense insufficient signal transduction activities or an overshoot in these activities.…”

Section: Adipokine Receptorsmentioning

confidence: 99%

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Schleinitz

2015

Rev Diabet Stud

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■ AbstractAdipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the "protective" allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed.

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Section: Adipokine Receptorsmentioning

confidence: 99%

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Schleinitz

2015

Rev Diabet Stud

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“…1). Such metabolic phenotyping studies are able to provide new insights into disease pathophysiology, and mechanisms that underlie differences in drug responses in the human population, which contribute to predicting both risk of toxicity and beneficial responses to drug treatment (Beger et al 2015; Cacciatore and Loda 2015; Everett 2015; Kaddurah-Daouk et al 2008; Kaddurah-Daouk and Weinshilboum 2014, 2015; Kastenmüller et al 2015; Nicholson et al 2012; Patti et al 2012; Su et al 2014; Suhre et al 2016; Wilson 2009; Zamboni et al 2015). Below we provide background information, concepts related to the use of metabolism data for disease and patient sub-classification, technologies that are available for metabolic profiling, their strengths, limitations and bottlenecks, and presently available tools for large scale studies in precision medicine.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics enables precision medicine: “A White Paper, Community Perspective”

et al. 2016

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Introduction: Background to metabolomicsMetabolomics is the comprehensive study of the metabolome, the repertoire of biochemicals (or small molecules) present in cells, tissues, and body fluids. The study of metabolism at the global or “-omics” level is a rapidly growing field that has the potential to have a profound impact upon medical practice. At the center of metabolomics, is the concept that a person’s metabolic state provides a close representation of that individual’s overall health status. This metabolic state reflects what has been encoded by the genome, and modified by diet, environmental factors, and the gut microbiome. The metabolic profile provides a quantifiable readout of biochemical state from normal physiology to diverse pathophysiologies in a manner that is often not obvious from gene expression analyses. Today, clinicians capture only a very small part of the information contained in the metabolome, as they routinely measure only a narrow set of blood chemistry analytes to assess health and disease states. Examples include measuring glucose to monitor diabetes, measuring cholesterol and high density lipoprotein/low density lipoprotein ratio to assess cardiovascular health, BUN and creatinine for renal disorders, and measuring a panel of metabolites to diagnose potential inborn errors of metabolism in neonates.Objectives of White Paper—expected treatment outcomes and metabolomics enabling tool for precision medicineWe anticipate that the narrow range of chemical analyses in current use by the medical community today will be replaced in the future by analyses that reveal a far more comprehensive metabolic signature. This signature is expected to describe global biochemical aberrations that reflect patterns of variance in states of wellness, more accurately describe specific diseases and their progression, and greatly aid in differential diagnosis. Such future metabolic signatures will: (1) provide predictive, prognostic, diagnostic, and surrogate markers of diverse disease states; (2) inform on underlying molecular mechanisms of diseases; (3) allow for sub-classification of diseases, and stratification of patients based on metabolic pathways impacted; (4) reveal biomarkers for drug response phenotypes, providing an effective means to predict variation in a subject’s response to treatment (pharmacometabolomics); (5) define a metabotype for each specific genotype, offering a functional read-out for genetic variants: (6) provide a means to monitor response and recurrence of diseases, such as cancers: (7) describe the molecular landscape in human performance applications and extreme environments. Importantly, sophisticated metabolomic analytical platforms and informatics tools have recently been developed that make it possible to measure thousands of metabolites in blood, other body fluids, and tissues. Such tools also enable more robust analysis of response to treatment. New insights have been gained about mechanisms of diseases, including neuropsychiatric disorders, cardiovascular disease, cancers...

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“…9 Metabolic phenotyping is becoming important in disease prevention due to its potential to identify individuals or sub-populations at risk, allowing for interventions (change in lifestyle, diet or appropriate medication) before the onset of the disease. 3 Metabolic phenotyping can be further utilized in personalized medicine for patient stratification by analysing predose biofluid metabolite profiles to predict drug effects, 10 which would increase the efficacy of treatment and decrease unwanted side effects.…”

Section: Introductionmentioning

confidence: 99%

Quantitativein vivoneurochemical profiling in humans: where are we now?

McKay

Tkáč

2016

Int. J. Epidemiol.

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Proton nuclear magnetic resonance spectroscopy of biofluids has become one of the key techniques for metabolic profiling and phenotyping. This technique has been widely used in a number of epidemiological studies and in a variety of health disorders. However, its utilization in brain disorders is limited due to the blood-brain barrier, which not only protects the brain from unwanted substances in the blood, but also substantially limits the potential of finding biomarkers for neurological disorders in serum. This review article focuses on the potential of localized in vivo proton magnetic resonance spectroscopy ( 1 H-MRS) for non-invasive neurochemical profiling in the human brain. First, methodological aspects of 1 H-MRS (data acquisition, processing and metabolite quantification) that are essential for reliable non-invasive neurochemical profiling are described. Second, the power of 1 H-MRS-based neurochemical profiling is demonstrated using some examples of its application in neuroscience and neurology. Finally, the authors present their vision and propose necessary steps to establish 1 H-MRS as a method suitable for large-scale neurochemical profiling in epidemiological research. Key words:1 H-MRS, methodology, spectral quality, neurochemical profiling, CNS disorders Key Messages• In vivo neurochemical profiling in the human brain is feasible, but the widespread use requires the implementation of the most advanced methodologies of 1 H-MRS.• There is a widening gap between what is feasible at specialized MR research centres and what is currently available for routine clinical practice.• The software upgrade (B 0 shimming, localization pulses sequence) on clinical 3T MR scanners is sufficient for a significant improvement of the 1 H-MRS data quality and for an increase in the range of reliably quantified metabolites.

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Pharmacometabonomics in Humans: A New Tool for Personalized Medicine

Cited by 89 publications

References 62 publications

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

Metabolomics enables precision medicine: “A White Paper, Community Perspective”

Quantitativein vivoneurochemical profiling in humans: where are we now?

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