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Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance
KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.ORCID-id: 0000-0002-6428-5936
KTH, Skolan för bioteknologi (BIO), Proteomik och nanobioteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
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2016 (Engelska)Ingår i: Cell Metabolism, ISSN 1550-4131, E-ISSN 1932-7420, Vol. 24, nr 1, s. 172-184Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Cell Press , 2016. Vol. 24, nr 1, s. 172-184
Nyckelord [en]
Protein Interaction Networks, Genome-Scale, Glucose-Tolerance, Metabolic Network, N-Glycosylation, Adipose-Tissue, Amino-Acid, Sensitivity, Models, Liver
Nationell ämneskategori
Cellbiologi
Identifikatorer
URN: urn:nbn:se:kth:diva-191751DOI: 10.1016/j.cmet.2016.05.026ISI: 000380793400022PubMedID: 27345421Scopus ID: 2-s2.0-84992391872OAI: oai:DiVA.org:kth-191751DiVA, id: diva2:970956
Forskningsfinansiär
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceKnut och Alice Wallenbergs StiftelseEU, FP7, Sjunde ramprogrammet
Anmärkning

QC 20160915

Tillgänglig från: 2016-09-15 Skapad: 2016-09-02 Senast uppdaterad: 2017-11-21Bibliografiskt granskad

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Lee, SunjaeZhang, ChengHallström, Björn M.Uhlèn, MathiasNielsen, Jens
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Proteomik och nanobioteknologiScience for Life Laboratory, SciLifeLabGenteknologi
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Cell Metabolism
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