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

Qing-Run Li; Zi-Ming Wang; Nicolai Jacob Wewer Albrechtsen; Dan-Dan Wang; Zhi-Duan Su; Xian-Fu Gao; Qing-Qing Wu; Hui-Ping Zhang; Li Zhu; Rong-Xia Li; SivHesse Jacobsen; Nils Bruun Jørgensen; Carsten Dirksen; Kirstine N. Bojsen-Møller; Jacob S. Petersen; Sten Madsbad; Trine R. Clausen; Børge Diderichsen; Luo-Nan Chen; Jens J. Holst; Rong Zeng; Jia-Rui Wu

doi:10.1016/j.ebiom.2018.01.018

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

Qing-Run Li, Zi-Ming Wang, Nicolai Jacob Wewer Albrechtsen, Dan-Dan Wang, Zhi-Duan Su, Xian-Fu Gao, Qing-Qing Wu, Hui-Ping Zhang, Li Zhu, Rong-Xia Li, SivHesse Jacobsen, Nils Bruun Jørgensen, Carsten Dirksen, Kirstine N. Bojsen-Møller, Jacob S. Petersen, Sten Madsbad, Trine R. Clausen, Børge Diderichsen, Luo-Nan Chen, Jens J. HolstRong Zeng, Jia-Rui Wu

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Abstract

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.

Original language	English
Journal	EBioMedicine
Volume	28
Pages (from-to)	234-240
Number of pages	7
ISSN	2352-3964
DOIs	https://doi.org/10.1016/j.ebiom.2018.01.018
Publication status	Published - 2018

Keywords

Journal Article
Obesity/genetics
Diabetes Mellitus, Type 2/blood
Gastric Bypass
Weight Loss
Humans
Metabolome
Gene Regulatory Networks
Principal Component Analysis
Systems Biology
Blood Proteins/metabolism
Gastric bypass surgery
Network biomarker
Systems biology
Network
Diabetes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ebiom.2018.01.018

Systems Signatures Reveal Unique Remission-path of Type 2 Diabetes Following Roux-en-Y Gastric Bypass SurgeryFinal published version, 2.55 MB

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Li, Q.-R., Wang, Z.-M., Albrechtsen, N. J. W., Wang, D.-D., Su, Z.-D., Gao, X.-F., Wu, Q.-Q., Zhang, H.-P., Zhu, L., Li, R.-X., Jacobsen, S., Jørgensen, N. B., Dirksen, C., Bojsen-Møller, K. N., Petersen, J. S., Madsbad, S., Clausen, T. R., Diderichsen, B., Chen, L.-N., ... Wu, J.-R. (2018). Systems signatures reveal unique remission-path of Type 2 diabetes following Roux-en-Y gastric bypass surgery. EBioMedicine, 28, 234-240. https://doi.org/10.1016/j.ebiom.2018.01.018

Li, Q-R, Wang, Z-M, Albrechtsen, NJW, Wang, D-D, Su, Z-D, Gao, X-F, Wu, Q-Q, Zhang, H-P, Zhu, L, Li, R-X, Jacobsen, S, Jørgensen, NB, Dirksen, C, Bojsen-Møller, KN, Petersen, JS, Madsbad, S, Clausen, TR, Diderichsen, B, Chen, L-N, Holst, JJ, Zeng, R & Wu, J-R 2018, 'Systems signatures reveal unique remission-path of Type 2 diabetes following Roux-en-Y gastric bypass surgery', EBioMedicine, vol. 28, pp. 234-240. https://doi.org/10.1016/j.ebiom.2018.01.018

@article{02afc2e84e624a8fa3e65b0e26127bae,

title = "Systems signatures reveal unique remission-path of Type 2 diabetes following Roux-en-Y gastric bypass surgery",

abstract = "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.",

keywords = "Journal Article, Obesity/genetics, Diabetes Mellitus, Type 2/blood, Gastric Bypass, Weight Loss, Humans, Metabolome, Gene Regulatory Networks, Principal Component Analysis, Systems Biology, Blood Proteins/metabolism, Gastric bypass surgery, Network biomarker, Systems biology, Network, Diabetes",

author = "Qing-Run Li and Zi-Ming Wang and Albrechtsen, {Nicolai Jacob Wewer} and Dan-Dan Wang and Zhi-Duan Su and Xian-Fu Gao and Qing-Qing Wu and Hui-Ping Zhang and Li Zhu and Rong-Xia Li and SivHesse Jacobsen and J{\o}rgensen, {Nils Bruun} and Carsten Dirksen and Bojsen-M{\o}ller, {Kirstine N.} and Petersen, {Jacob S.} and Sten Madsbad and Clausen, {Trine R.} and B{\o}rge Diderichsen and Luo-Nan Chen and Holst, {Jens J.} and Rong Zeng and Jia-Rui Wu",

note = "Copyright {\textcopyright} 2018. Published by Elsevier B.V.",

year = "2018",

doi = "10.1016/j.ebiom.2018.01.018",

language = "English",

volume = "28",

pages = "234--240",

journal = "EBioMedicine",

issn = "2352-3964",

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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

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

SN - 2352-3964

VL - 28

SP - 234

EP - 240

JO - EBioMedicine

JF - EBioMedicine

ER -

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

Abstract

Keywords

UN SDGs

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