Urinary biomarkers of physical activity: candidates and clinical utility

Sampson, Dayle; Broadbent, James A.; Parker, Anthony W.; Upton, Zee; Parker, Tony J.

doi:10.1586/14789450.2014.859527

Cited by 17 publications

(12 citation statements)

References 154 publications

(128 reference statements)

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“…Thus, the establishment of less-invasive and technically uncomplicated biomarker(s) to monitor the disease-stage and the outcome of therapeutic treatment(s) is urgently needed. There is also an unmet need to establish biomarkers to investigate exercise-related muscle damage and repair processes30313940. To resolve these situations, in this study, we developed an ELISA to measure titin N-terminal fragment in human urine, and we demonstrated that the established ELISA is highly sensitive and available for the detection of a wide range of concentrations of titin N-terminal fragment in urine.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Maruyama

Asai

Abê

et al. 2016

Sci Rep

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Muscle damage and loss of muscle mass are triggered by immobilization, loss of appetite, dystrophies and chronic wasting diseases. In addition, physical exercise causes muscle damage. In damaged muscle, the N-terminal and C-terminal regions of titin, a giant sarcomere protein, are cleaved by calpain-3, and the resulting fragments are excreted into the urine via glomerular filtration. Therefore, we considered titin fragments as promising candidates for reliable and non-invasive biomarkers of muscle injury. Here, we established a sandwich ELISA that can measure the titin N-terminal fragment over a biologically relevant range of concentrations, including those in urine samples from older, non-ambulatory Duchenne muscular dystrophy patients and from healthy donors under everyday life conditions and after exercise. Our results indicate that the established ELISA could be a useful tool for the screening of muscular dystrophies and also for monitoring the progression of muscle disease, evaluating the efficacy of therapeutic approaches, and investigating exercise-related sarcomeric disruption and repair processes.

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Section: Discussionmentioning

confidence: 99%

Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Maruyama

Asai

Abê

et al. 2016

Sci Rep

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“…; Claus and Swann ; Sampson et al. ). The low sample volumes required and the amount of information obtained make these approaches attractive for efficiently advancing understanding of the role of nutrition in modulating metabolic responses to military training, identifying novel relationships between nutrition, metabolism, and performance decrements in these environments, and monitoring the temporal dynamics of these relationships.…”

Section: Discussionmentioning

confidence: 99%

“…This approach can provide more comprehensive and sensitive markers of metabolic status than commonly measured biomarkers while offering insights into the regulation of metabolic pathways (Sampson et al. ). Metabolomics may therefore provide an efficient method of assessing dynamic metabolic responses to stress and nutritional interventions during military training, and for identifying novel mechanisms modulating performance in these environments (Bradburne et al.…”

Section: Introductionmentioning

confidence: 99%

Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis

et al. 2017

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Military training studies provide unique insight into metabolic responses to extreme physiologic stress induced by multiple stressor environments, and the impacts of nutrition in mediating these responses. Advances in metabolomics have provided new approaches for extending current understanding of factors modulating dynamic metabolic responses in these environments. In this study, whole‐body metabolic responses to strenuous military training were explored in relation to energy balance and macronutrient intake by performing nontargeted global metabolite profiling on plasma collected from 25 male soldiers before and after completing a 4‐day, 51‐km cross‐country ski march that produced high total daily energy expenditures (25.4 MJ/day [SD 2.3]) and severe energy deficits (13.6 MJ/day [SD 2.5]). Of 737 identified metabolites, 478 changed during the training. Increases in 88% of the free fatty acids and 91% of the acylcarnitines, and decreases in 88% of the mono‐ and diacylglycerols detected within lipid metabolism pathways were observed. Smaller increases in 75% of the tricarboxylic acid cycle intermediates, and 50% of the branched‐chain amino acid metabolites detected were also observed. Changes in multiple metabolites related to lipid metabolism were correlated with body mass loss and energy balance, but not with energy and macronutrient intakes or energy expenditure. These findings are consistent with an increase in energy metabolism, lipolysis, fatty acid oxidation, ketogenesis, and branched‐chain amino acid catabolism during strenuous military training. The magnitude of the energy deficit induced by undereating relative to high energy expenditure, rather than macronutrient intake, appeared to drive these changes, particularly within lipid metabolism pathways.

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“…Especially urine proteomics has great potential for discovering new disease indicators that are suitable for the establishment of simple and non-invasive assays [232]. The comparative profiling of the urine proteome has already identified several urinary biomarkers of physical activity [233] and muscle wasting during cancer cachexia [234].…”

Section: Circulating Biomarkers For Monitoring General Muscle Damagementioning

confidence: 99%

Mass Spectrometry-Based Identification of Muscle-Associated and Muscle-Derived Proteomic Biomarkers of Dystrophinopathies

Dowling

Holland

Ohlendieck

2014

Journal of Neuromuscular Diseases

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The optimization of large-scale screening procedures of pathological specimens by genomic, proteomic and metabolic methods has drastically increased the bioanalytical capability for swiftly identifying novel biomarkers of inherited disorders, such as neuromuscular diseases. X-linked muscular dystrophy represents the most frequently inherited muscle disease and is characterized by primary abnormalities in the membrane cytoskeletal protein dystrophin. Mass spectrometry-based proteomics has been widely employed for the systematic analysis of dystrophin-deficient muscle tissues, using patient samples and animal models of dystrophinopathy. Both, gel-based methods and label-free mass spectrometric techniques have been applied in comparative analyses and established a large number of altered proteins that are associated with muscle contraction, energy metabolism, ion homeostasis, cellular signaling, the cytoskeleton, the extracellular matrix and the cellular stress response. Although these new indicators of muscular dystrophy have increased our general understanding of the molecular pathogenesis of dystrophinopathy, their application as new diagnostic or prognostic biomarkers would require the undesirable usage of invasive methodology. Hence, to reduce the need for diagnostic muscle biopsy procedures, more recent efforts have focused on the proteomic screening of suitable body fluids, such as plasma, serum or urine, for the identification of changed concentration levels of muscle-derived peptides, protein fragments or intact proteins. The occurrence of muscular dystrophy-related protein species in biofluids will be extremely helpful for the future development of cost-effective and non-invasive diagnostic procedures. Novel biomarker signatures of dystrophinopathies will be indispensible for the swift evaluation of innovative therapeutic approaches, such as exon skipping, codon-read-through or stem cell therapy.

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Urinary biomarkers of physical activity: candidates and clinical utility

Cited by 17 publications

References 154 publications

Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Establishment of a highly sensitive sandwich ELISA for the N-terminal fragment of titin in urine

Military training elicits marked increases in plasma metabolomic signatures of energy metabolism, lipolysis, fatty acid oxidation, and ketogenesis

Mass Spectrometry-Based Identification of Muscle-Associated and Muscle-Derived Proteomic Biomarkers of Dystrophinopathies

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