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

Cell Metab. 2016 Jul 12;24(1):172-84. doi: 10.1016/j.cmet.2016.05.026. Epub 2016 Jun 23.

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.

Keywords: genome-scale metabolic models; insulin resistance; mannose; obesity; protein-protein interaction networks; transcriptional regulatory networks.

MeSH terms

  • Adult
  • Bariatric Surgery
  • Case-Control Studies
  • Female
  • Fructose / metabolism
  • Gene Expression Profiling
  • Gene Regulatory Networks*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion
  • Male
  • Mannose / blood*
  • Metabolic Networks and Pathways*
  • Obesity / blood
  • Protein Interaction Maps*
  • Proteomics

Substances

  • Insulin
  • Fructose
  • Mannose