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Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
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2016 (English)In: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 24, no 1, 172-184 p.Article in journal (Refereed) Published
Abstract [en]

To investigate the biological processes that are altered in obese subjects, we generated cell-specific integrated networks (INs) by merging genome-scale metabolic, transcriptional regulatory and protein-protein interaction networks. We performed genome-wide transcriptomics analysis to determine the global gene expression changes in the liver and three adipose tissues from obese subjects undergoing bariatric surgery and integrated these data into the cell-specific INs. We found dysregulations in mannose metabolism in obese subjects and validated our predictions by detecting mannose levels in the plasma of the lean and obese subjects. We observed significant correlations between plasma mannose levels, BMI, and insulin resistance (IR). We also measured plasma mannose levels of the subjects in two additional different cohorts and observed that an increased plasma mannose level was associated with IR and insulin secretion. We finally identified mannose as one of the best plasma metabolites in explaining the variance in obesity-independent IR.

Place, publisher, year, edition, pages
Cell Press , 2016. Vol. 24, no 1, 172-184 p.
Keyword [en]
Protein Interaction Networks, Genome-Scale, Glucose-Tolerance, Metabolic Network, N-Glycosylation, Adipose-Tissue, Amino-Acid, Sensitivity, Models, Liver
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:kth:diva-191751DOI: 10.1016/j.cmet.2016.05.026ISI: 000380793400022PubMedID: 27345421OAI: oai:DiVA.org:kth-191751DiVA: diva2:970956
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut and Alice Wallenberg FoundationEU, FP7, Seventh Framework Programme
Note

QC 20160915

Available from: 2016-09-15 Created: 2016-09-02 Last updated: 2016-09-15Bibliographically approved

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