Defining the Human Adipose Tissue Proteome To Reveal Metabolic Alterations in Obesity
2014 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, no 11, 5106-5119 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2014. Vol. 13, no 11, 5106-5119 p.
white adipose tissue, adipocytes, transcriptome, proteome, genome-scale metabolic modeling
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:kth:diva-157609DOI: 10.1021/pr500586eISI: 000344636500055PubMedID: 25219818ScopusID: 2-s2.0-84908884352OAI: oai:DiVA.org:kth-157609DiVA: diva2:771162
FunderKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework ProgrammeScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
QC 201412122014-12-122014-12-112014-12-12Bibliographically approved