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Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance

Journal article
Authors S. Lee
C. Zhang
M. Kilicarslan
B. D. Piening
Elias Björnson
B. M. Hallstrom
A. K. Groen
E. Ferrannini
M. Laakso
M. Snyder
M. Bluher
M. Uhlen
Jens B. Nielsen
Ulf Smith
M. J. Serlie
Jan Borén
Adil Mardinoglu
Published in Cell Metabolism
Volume 24
Issue 1
Pages 172-184
ISSN 1550-4131
Publication year 2016
Published at Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 172-184
Language en
Links dx.doi.org/10.1016/j.cmet.2016.05.0...
Keywords protein interaction networks, genome-scale, glucose-tolerance, metabolic, network, n-glycosylation, adipose-tissue, amino-acid, sensitivity, models, liver, Cell Biology, Endocrinology & Metabolism
Subject categories Endocrinology and Diabetes, Cell Biology

Abstract

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.

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