Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 28, 2020; 26(20): 2599-2617
Published online May 28, 2020. doi: 10.3748/wjg.v26.i20.2599
Sleeve gastrectomy ameliorates endothelial function and prevents lung cancer by normalizing endothelin-1 axis in obese and diabetic rats
Rexiati Ruze, Ya-Cheng Xiong, Jian-Wen Li, Ming-Wei Zhong, Qian Xu, Zhi-Bo Yan, Jian-Kang Zhu, Yu-Gang Cheng, San-Yuan Hu, Guang-Yong Zhang
Rexiati Ruze, Ya-Cheng Xiong, Qian Xu, Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China
Jian-Wen Li, Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
Ming-Wei Zhong, Jian-Kang Zhu, Yu-Gang Cheng, San-Yuan Hu, Guang-Yong Zhang, Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, Shandong Province, China
Zhi-Bo Yan, Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Zhang GY and Hu SY conceived of the experiments; Zhang GY and Li JW designed the experiments; Zhong MW, Zhu JK, and Cheng YG performed the literature research; Ruze R and Xiong YC carried out the experiments; Xu Q and Yan ZB performed the statistical analyses; Ruze R prepared the manuscript; Zhang GY gave final approval of the submitted and published versions.
Supported by National Natural Science Foundation of China, No. 81370496 and No. 81873647; Youth Program of National Natural Science Foundation of China, No. 81600059.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of The First Affiliated Hospital of Shandong First Medical University, Jinan, China (2020-S307).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee on Animal Experiment of The First Affiliated Hospital of Shandong First Medical University (2020-S307).
Conflict-of-interest statement: All authors declare that they have no conflicts of interest related to this study.
Data sharing statement: Research data of the current study is available at the Mendeley Data Depository, under: Ruzi, Rishat; Xiong, Yacheng; Li, Jianwen; Zhong, Mingwei; Xu, Qian; Yan, Zhibo; Zhu, Jiankang; Cheng, Yugang; Hu, Sanyuan; Zhang, Guangyong (2020), “Data for: Sleeve Gastrectomy Ameliorates Endothelial Function and Prevents Lung Cancer by Normalizing Endothelin-1 Axis and Reduces DNA damage in Obese and Diabetic Rats”, Mendeley Data, v3.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Guang-Yong Zhang, DSc, MD, PhD, Chief Doctor, Professor, Department of General Surgery, The First Affiliated Hospital of Shandong First Medical University, No. 16766, Jingshi Road, Jinan 250014, Shandong Province, China.
Received: March 14, 2020
Peer-review started: March 14, 2020
First decision: April 12, 2020
Revised: April 13, 2020
Accepted: May 15, 2020
Article in press: May 15, 2020
Published online: May 28, 2020
Research background

Although it is stated that bariatric surgeries are capable of preventing numerous types of cardiovascular diseases and cancer, the basic studies are still warranted to explain such roles by revealing the possible mechanisms. Herein, an attempt was made to answer these questions in an innovative way by investigating one of the important regulation systems in the body – the endothelin-1 (ET-1) axis.

Research motivation

Providing evidence for the lowered risk of cardiovascular disease and cancer will not only enlighten the multifunctional effects of sleeve gastrectomy (SG), which is deemed to be “metabolic”, but also broaden and deepen our understanding of related fields and help improve the acceptance of SG as well.

Research objectives

In the current study, an ameliorated status of the ET-1 axis was confirmed, indicating the improvement in endothelial function and decline in the risk of lung cancer. Plus, the latter was also identified by the decreased level of DNA damage. Collectively, these findings are bound to attract and inspire future researchers to look for the clues of the benefits brought by bariatric surgeries that extend beyond the known metabolic improvements.

Research methods

SG and sham surgery were performed to clarify the effect induced on the ET-1 axis. In order to determine the real baseline of the parameters, healthy controls were also included. Moreover, the γ-H2AX foci assay was applied to provide stronger evidence of SG in preventing lung cancer, which was not an approach used commonly in previous research related to bariatric surgeries.

Research results

The results indicated that SG improved endothelial function and prevented lung cancer by normalizing the ET-1 axis, providing animal-based findings and suggesting new perspectives for the clinical field. The potential mechanisms of how SG effects the ET-1 axis and whether it is a direct impact or achieved by moderating metabolic disorder, however, need to be explored further.

Research conclusions

Beyond reducing body weight and improving both glycometabolism and insulin sensitivity, SG improves endothelial function and exerts a protective role in preventing lung cancer by normalizing the ET-1 axis and lessening DNA damage. These findings may present a new theoretical basis for clinical implications of SG.

Research perspectives

We believe that looking for more lines of evidence which expand our knowledge beyond the metabolic impact of bariatric surgeries is important, particularly because it will illuminate and illustrate the whole picture of the therapeutic effects of these procedures. Undoubtedly, factors that change under metabolic disorder and contribute to canceration, are the entry points and keys to the answer.