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

Previous evidence has implied that obesity is an independent risk factor for developing cancer. Being closely related to obesity, type 2 diabetes mellitus provides a suitable environment for the formation and metastasis of tumors through multiple pathways. Although bariatric surgeries are effective in preventing and lowering the risk of various types of cancer, the underlying mechanisms of this effect are not clearly elucidated.


To uncover the role and effect of sleeve gastrectomy (SG) in preventing lung cancer in obese and diabetic rats.


SG was performed on obese and diabetic Wistar rats, and the postoperative transcriptional and translational alterations of the endothelin-1 (ET-1) axis in the lungs were compared to sham-operated obese and diabetic rats and age-matched healthy controls to assess the improvements in endothelial function and risk of developing lung cancer at the postoperative 4th, 8th, and 12th weeks. The risk was also evaluated using nuclear phosphorylation of H2A histone family member X as a marker of DNA damage (double-strand break).


Compared to obese and diabetic sham-operated rats, SG brought a significant reduction to body weight, food intake, and fasting blood glucose while improving oral glucose tolerance and insulin sensitivity. In addition, ameliorated levels of gene and protein expression in the ET-1 axis as well as reduced DNA damage indicated improved endothelial function and a lower risk of developing lung cancer after the surgery.


Apart from eliminating metabolic disorders, SG improves endothelial function and plays a protective role in preventing lung cancer via normalized ET-1 axis and reduced DNA damage.

Keywords: Sleeve gastrectomy, Lung cancer, Endothelin-1 axis, Endothelial dysfunction, DNA damage, Obesity

Core tip: To explore the potential mechanism of bariatric surgery to reduce the risk of cancer, sleeve gastrectomy (SG) was performed on obese and diabetic rats. As a result, with a disrupted endothelin-1 axis, sham-operated subjects manifested deteriorated endothelial function and an increased risk of developing cancer compared to the healthy controls. However, far more than improving glycometabolism, SG reversed these negative effects by normalizing the endothelin-1 axis and reducing DNA damage, which contributed to the effects of SG to ameliorate endothelial function and prevent lung cancer.