TY - JOUR

T1 - Systems signatures reveal unique remission-path of Type 2 diabetes following Roux-en-Y gastric bypass surgery

AU - Li, Qing-Run

AU - Wang, Zi-Ming

AU - Albrechtsen, Nicolai Jacob Wewer

AU - Wang, Dan-Dan

AU - Su, Zhi-Duan

AU - Gao, Xian-Fu

AU - Wu, Qing-Qing

AU - Zhang, Hui-Ping

AU - Zhu, Li

AU - Li, Rong-Xia

AU - Jacobsen, SivHesse

AU - Jørgensen, Nils Bruun

AU - Dirksen, Carsten

AU - Bojsen-Møller, Kirstine N.

AU - Petersen, Jacob S.

AU - Madsbad, Sten

AU - Clausen, Trine R.

AU - Diderichsen, Børge

AU - Chen, Luo-Nan

AU - Holst, Jens J.

AU - Zeng, Rong

AU - Wu, Jia-Rui

N1 - Copyright © 2018. Published by Elsevier B.V.

PY - 2018

Y1 - 2018

N2 - Roux-en-Y Gastric bypass surgery (RYGB) is emerging as a powerful tool for treatment of obesity and may also cause remission of type 2 diabetes. However, the molecular mechanism of RYGB leading to diabetes remission independent of weight loss remains elusive. In this study, we profiled plasma metabolites and proteins of 10 normal glucose-tolerant obese (NO) and 9 diabetic obese (DO) patients before and 1-week, 3-months, 1-year after RYGB. 146 proteins and 128 metabolites from both NO and DO groups at all four stages were selected for further analysis. By analyzing a set of bi-molecular associations among the corresponding network of the subjects with our newly developed computational method, we defined the represented physiological states (called the edge-states that reflect the interactions among the bio-molecules), and the related molecular networks of NO and DO patients, respectively. The principal component analyses (PCA) revealed that the edge states of the post-RYGB NO subjects were significantly different from those of the post-RYGB DO patients. Particularly, the time-dependent changes of the molecular hub-networks differed between DO and NO groups after RYGB. In conclusion, by developing molecular network-based systems signatures, we for the first time reveal that RYGB generates a unique path for diabetes remission independent of weight loss.

AB - Roux-en-Y Gastric bypass surgery (RYGB) is emerging as a powerful tool for treatment of obesity and may also cause remission of type 2 diabetes. However, the molecular mechanism of RYGB leading to diabetes remission independent of weight loss remains elusive. In this study, we profiled plasma metabolites and proteins of 10 normal glucose-tolerant obese (NO) and 9 diabetic obese (DO) patients before and 1-week, 3-months, 1-year after RYGB. 146 proteins and 128 metabolites from both NO and DO groups at all four stages were selected for further analysis. By analyzing a set of bi-molecular associations among the corresponding network of the subjects with our newly developed computational method, we defined the represented physiological states (called the edge-states that reflect the interactions among the bio-molecules), and the related molecular networks of NO and DO patients, respectively. The principal component analyses (PCA) revealed that the edge states of the post-RYGB NO subjects were significantly different from those of the post-RYGB DO patients. Particularly, the time-dependent changes of the molecular hub-networks differed between DO and NO groups after RYGB. In conclusion, by developing molecular network-based systems signatures, we for the first time reveal that RYGB generates a unique path for diabetes remission independent of weight loss.

KW - Journal Article

KW - Obesity/genetics

KW - Diabetes Mellitus, Type 2/blood

KW - Gastric Bypass

KW - Weight Loss

KW - Humans

KW - Metabolome

KW - Gene Regulatory Networks

KW - Principal Component Analysis

KW - Systems Biology

KW - Blood Proteins/metabolism

KW - Gastric bypass surgery

KW - Network biomarker

KW - Systems biology

KW - Network

KW - Diabetes

U2 - 10.1016/j.ebiom.2018.01.018

DO - 10.1016/j.ebiom.2018.01.018

M3 - Journal article

C2 - 29422288

VL - 28

SP - 234

EP - 240

JO - EBioMedicine

JF - EBioMedicine

SN - 2352-3964

ER -