Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance
Artikel i vetenskaplig tidskrift, 2016

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.

protein interaction networks

liver

amino-acid

glucose-tolerance

n-glycosylation

Cell Biology

sensitivity

metabolic

Endocrinology & Metabolism

models

network

adipose-tissue

genome-scale

Författare

SangWook Lee

Kungliga Tekniska Högskolan (KTH)

C. Zhang

Kungliga Tekniska Högskolan (KTH)

M. Kilicarslan

Universiteit Van Amsterdam

B. D. Piening

Stanford University

Elias Björnson

Göteborgs universitet

Chalmers, Biologi och bioteknik, Systembiologi

B. M. Hallstrom

Kungliga Tekniska Högskolan (KTH)

A. K. Groen

Rijksuniversiteit Groningen

E. Ferrannini

Istituto di Fisiologia Clinica del CNR

M. Laakso

Itä-Suomen Yliopisto

M. Snyder

Stanford University

M. Bluher

Universität Leipzig

M. Uhlen

Kungliga Tekniska Högskolan (KTH)

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Ulf Smith

Göteborgs universitet

M. J. Serlie

Universiteit Van Amsterdam

Jan Borén

Göteborgs universitet

Adil Mardinoglu

Chalmers, Biologi och bioteknik, Systembiologi

Cell Metabolism

1550-4131 (ISSN)

Vol. 24 172-184

Ämneskategorier

Endokrinologi och diabetes

Cellbiologi

Styrkeområden

Livsvetenskaper och teknik

DOI

10.1016/j.cmet.2016.05.026

PubMed

27345421