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Proteome- and Trans...
Proteome- and Transcriptome-Driven Reconstruction of the Human Myocyte Metabolic Network and Its Use for Identification of Markers for Diabetes
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Väremo, Leif (author)
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- Scheele, Camilla (author)
- Köpenhamns universitet,University of Copenhagen
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- Broholm, Christa (author)
- Köpenhamns universitet,University of Copenhagen
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- Mardinoglu, Adil, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Kampf, Caroline (author)
- Uppsala universitet,Uppsala University
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- Asplund, Anna (author)
- Uppsala universitet,Uppsala University
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- Nookaew, Intawat, 1977 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Uhlén, Mathias (author)
- Uppsala universitet,KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Science for Life Laboratory, SciLifeLab,Institutionen för immunologi, genetik och patologi,Alba Nova Universitetscentrum,AlbaNova University Center. Stockholm Center for Physics, Astronomy and Biotechnology,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Pedersen, Bente Klarlund (author)
- Köpenhamns universitet,University of Copenhagen
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- Nielsen, Jens (author)
- KTH,Genteknologi,Chalmers University of Technology, Sweden,Chalmers tekniska högskola
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- Wigge, Leif, 1986 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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(creator_code:org_t)
- Elsevier BV, 2015
- 2015
- English.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 11:6, s. 921-933
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Abstract
Subject headings
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- Skeletal myocytes are metabolically active and susceptible to insulin resistance and are thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes, and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network context for the integration of high-throughput data. We generated myocyte-specific RNA-sequencing data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the downregulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Bioinformatik och systembiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Bioinformatics and Systems Biology (hsv//eng)
Keyword
- Gene-Set Analysis
- Insulin-Resistance
- Skeletal-Muscle
- Expression Data
- Oxidative-Phosphorylation
- Amino-Acids
- Integration
- Obesity
- Quantification
- Hyperglycemia
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Väremo, Leif
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Scheele, Camilla
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Broholm, Christa
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Mardinoglu, Adil ...
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Kampf, Caroline
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Asplund, Anna
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show more...
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Nookaew, Intawat ...
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Uhlén, Mathias
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Pedersen, Bente ...
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Nielsen, Jens
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Wigge, Leif, 198 ...
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Bioinformatics a ...
- Articles in the publication
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Cell Reports
- By the university
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Royal Institute of Technology
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Uppsala University
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Chalmers University of Technology