Integrated Networks

Integrated network analysis reveals an association between plasma mannose levels and insulin resistance

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, body mass index (BMI) and insulin resistance (IR). We also measured plasma mannose levels of the subjects in additional two 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 metabolite in explaining the variance in obesity-independent IR.


Download INs for liver, adipose and muscle tissues for lean and obese subjects.

INs for lean subjects:

INs for obese subjects:

RNs for lean subjects:

RNs for obese subjects:

PPINs for lean subjects:

PPINs for obese subjects: