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A Multivariate Screening Strategy for Investigating Metabolic Effects of Strenuous Physical Exercise in Human Serum
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
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2007 (Engelska)Ingår i: Journal of Proteome Research, ISSN 1535-3893, Vol. 6, nr 6, s. 2113-2120Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

A novel hypothesis-free multivariate screening methodology for the study of human exercise metabolism in blood serum is presented. Serum gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) data was processed using hierarchical multivariate curve resolution (H-MCR), and orthogonal partial least-squares discriminant analysis (OPLS-DA) was used to model the systematic variation related to the acute effect of strenuous exercise. Potential metabolic biomarkers were identified using data base comparisons. Extensive validation was carried out including predictive H-MCR, 7-fold full cross-validation, and predictions for the OPLS-DA model, variable permutation for highlighting interesting metabolites, and pairwise t tests for examining the significance of metabolites. The concentration changes of potential biomarkers were verified in the raw GC/TOFMS data. In total, 420 potential metabolites were resolved in the serum samples. On the basis of the relative concentrations of the 420 resolved metabolites, a valid multivariate model for the difference between pre- and post-exercise subjects was obtained. A total of 34 metabolites were highlighted as potential biomarkers, all statistically significant (p < 8.1E-05). As an example, two potential markers were identified as glycerol and asparagine. The concentration changes for these two metabolites were also verified in the raw GC/TOFMS data.The strategy was shown to facilitate interpretation and validation of metabolic interactions in human serum as well as revealing the identity of potential markers for known or novel mechanisms of human exercise physiology. The multivariate way of addressing metabolism studies can help to increase the understanding of the integrative biology behind, as well as unravel new mechanistic explanations in relation to, exercise physiology.

Ort, förlag, år, upplaga, sidor
American Chemical Society , 2007. Vol. 6, nr 6, s. 2113-2120
Nyckelord [en]
Chemometrics, Exercise, GC/MS, Human Metabolism, Metabolomics, Metabonomics, Physiology, Predictive, Screening, Serum
Identifikatorer
URN: urn:nbn:se:umu:diva-13191DOI: 10.1021/pr070007gPubMedID: 17428078OAI: oai:DiVA.org:umu-13191DiVA, id: diva2:152862
Tillgänglig från: 2007-09-28 Skapad: 2007-09-28 Senast uppdaterad: 2018-06-09Bibliografiskt granskad
Ingår i avhandling
1. Mapping the consequenses of physical exercise and nutrition on human health: A predictive metabolomics approach
Öppna denna publikation i ny flik eller fönster >>Mapping the consequenses of physical exercise and nutrition on human health: A predictive metabolomics approach
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Human health is a complex and wide-ranging subject far beyond nutrition and physical exercise. Still, these factors have a huge impact on global health by their ability to prevent diseases and thus promote health. Thus, to identify health risks and benefits, it is necessary to reveal the underlying mechanisms of nutrition and exercise, which in many cases follows a complex chain of events. As a consequence, current health research is generating massive amounts of data from anthropometric parameters, genes, proteins, small molecules (metabolites) et cetera, with the intent to understand these mechanisms. For the study of health responses, especially related to physical exercise and nutrition, alterations in small molecules (metabolites) are in most cases immediate and located close to the phenotypic level and could therefore provide early signs of metabolic imbalances. Since there are roughly as many different responses to exercise and nutrients as there are humans, this quest is highly multifaceted and will benefit from an interpretation of treatment effects on a general as well as on an individual level. This thesis involves the application of chemometric methods to the study of global metabolic reactions, i.e. metabolomics, in a strategy coined predictive metabolomics. Via the application of predictive metabolomics an extensive hypothesis-free biological interpretation has been carried out of metabolite patterns in blood, acquired using gas chromatography-mass spectrometry (GC-MS), related to physical exercise, nutrition and diet, all in the context of human health. In addition, the chemometrics methodology have computational benefits concerning the extraction of relevant information from information-rich data as well as for interpreting general treatment effects and individual responses, as exemplified throughout this work. Health concerns all lifestages, thus this thesis presents a strategic framework in combination with comprehensive interpretations of metabolite patterns throughout life. This includes a broad range of human studies revealing metabolic patterns related to the impact of physical exercise, macronutrient modulation and different fitness status in young healthy males, short and long term dietary treatments in overweight post menopausal women as well as metabolic responses related to probiotics treatment and early development in infants. As a result, the studies included in the thesis have revealed metabolic patterns potentially indicative of an anti-catabolic response to macronutrients in the early recovery phase following exercise. Moreover, moderate differences in the metabolome associated with cardiorespiratory fitness level were detected, which could be linked to variation in the inflammatory and antioxidaive defense system. This work also highlighted mechanistic information that could be connected to dietary related weight loss in overweight and obese postmenopausal women in relation to short as well as long term dietary effects based on different macronutrient compositions. Finally, alterations were observed in metabolic profiles in relation to probiotics treatment in the second half of infancy, suggesting possible health benefits of probiotics supplementation at an early age.

 

Ort, förlag, år, upplaga, sidor
Umeå: Print och Media, 2011. s. 60
Nyckelord
Metabolomics, physical exercise, cardiorespiratory fitness nutrition, high protein and fat diet, Lactobacillus F19, probiotics, GC-MS, plasma, chemometrics, multivariate analysis statistical experimental design, design of experiments
Nationell ämneskategori
Annan medicinsk grundvetenskap
Forskningsämne
systemanalys; näringslära; molekylär medicin (medicinska vetenskaper)
Identifikatorer
urn:nbn:se:umu:diva-43844 (URN)978-91-7459-128-6 (ISBN)
Disputation
2011-06-03, KB3B1, KBC-huset, Umeå universitet, Umeå, 10:00 (Engelska)
Opponent
Handledare
Anmärkning
Embargo until 2012-06-01Tillgänglig från: 2011-05-12 Skapad: 2011-05-12 Senast uppdaterad: 2018-06-08Bibliografiskt granskad

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Chorell, ElinThysell, ElinJonsson, PärSvensson, MichaelAntti, Henrik

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Chorell, ElinThysell, ElinJonsson, PärSvensson, MichaelAntti, Henrik
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Kemiska institutionenInstitutionen för kirurgisk och perioperativ vetenskapUmeå Plant Science Centre (UPSC)Idrottsmedicin

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