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

Sunjae Lee, Cheng Zhang, Murat Kilicarslan, Brian D. Piening, Elias Bjornson, Bjorn M. Hallstrom, Albert K. Groen, Ele Ferrannini, Markku Laakso, Michael Snyder, Matthias Bluher, Mathias Uhlen, Jens Nielsen, Ulf Smith, Mireille J. Serlie, Jan Boren, Adil Mardinoglu*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)172-184
Number of pages13
JournalCell metabolism
Volume24
Issue number1
DOIs
Publication statusPublished - 12-Jul-2016

Keywords

  • PROTEIN INTERACTION NETWORKS
  • GENOME-SCALE
  • GLUCOSE-TOLERANCE
  • METABOLIC NETWORK
  • N-GLYCOSYLATION
  • ADIPOSE-TISSUE
  • AMINO-ACID
  • SENSITIVITY
  • MODELS
  • LIVER

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