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Defining the Human ...
Defining the Human Adipose Tissue Proteome To Reveal Metabolic Alterations in Obesity
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- Mardinoglu, Adil, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Kampf, Caroline (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Uppsala University
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- Asplund, Anna (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Uppsala University
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- Fagerberg, Linn (author)
- KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Hallström, Björn M. (author)
- KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Edlund, Karolina (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Uppsala University
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- Blüher, Matthias (author)
- Universität Leipzig,Leipzig University
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- Pontén, Fredrik (author)
- Uppsala universitet,Molekylär och morfologisk patologi,Uppsala University
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- Uhlén, Mathias (author)
- KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab,Kungliga Tekniska Högskolan (KTH),Royal Institute of Technology (KTH)
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- Nielsen, Jens (author)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Chalmers University of Technology, Sweden,Chalmers tekniska högskola
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(creator_code:org_t)
- 2014-09-25
- 2014
- English.
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:11, s. 5106-5119
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https://urn.kb.se/re...
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Abstract
Subject headings
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- White adipose tissue (WAT) has a major role in the progression of obesity. Here, we combined data from RNA-Seq and antibody-based immunohistochemistry to describe the normal physiology of human WAT obtained from three female subjects and explored WAT-specific genes by comparing WAT to 26 other major human tissues. Using the protein evidence in WAT, we validated the content of a genome-scale metabolic model for adipocytes. We employed this high-quality model for the analysis of subcutaneous adipose tissue (SAT) gene expression data obtained from subjects included in the Swedish Obese Subjects Sib Pair study to reveal molecular differences between lean and obese individuals. We integrated SAT gene expression and plasma metabolomics data, investigated the contribution of the metabolic differences in the mitochondria of SAT to the occurrence of obesity, and eventually identified cytosolic branched-chain amino acid (BCAA) transaminase 1 as a potential target that can be used for drug development. We observed decreased glutaminolysis and alterations in the BCAAs metabolism in SAT of obese subjects compared to lean subjects. We also provided mechanistic explanations for the changes in the plasma level of BCAAs, glutamate, pyruvate, and alpha-ketoglutarate in obese subjects. Finally, we validated a subset of our model-based predictions in 20 SAT samples obtained from 10 lean and 10 obese male and female subjects.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- white adipose tissue
- adipocytes
- transcriptome
- proteome
- genome-scale metabolic modeling
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Mardinoglu, Adil ...
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Kampf, Caroline
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Asplund, Anna
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Fagerberg, Linn
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Hallström, Björn ...
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Edlund, Karolina
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show more...
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Blüher, Matthias
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Pontén, Fredrik
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Uhlén, Mathias
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Nielsen, Jens
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show less...
- 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 Biochemistry and ...
- Articles in the publication
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Journal of Prote ...
- 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