Oxidative stress collaboratively induced by obesity and acid reflux promotes development of Barrett's esophagus

2022 Fiscal Year Final Research Report

• Project/Area Number: 18K07992
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Tohoku University
• Principal Investigator: Asanuma Kiyotaka 東北大学, 医学系研究科, 大学院非常勤講師 (10431553)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Keywords: 肥満 / GERD / 酸化ストレス / バレット食道 / 食道腺癌

Outline of Final Research Achievements

The aim of this study is to demonstrate that Barrett's esophagus, a risk factor for esophageal adenocarcinoma, is enhanced and promoted by the synergistic effects of obesity and GERD (gastroesophageal reflux disease) through increased oxidative stress. In rat studies, leptin, an obesity-related hormone, exacerbated esophageal mucosal injury caused by GERD by inducing mucosal infiltration of T cells and increasing the secretion of inflammatory cytokines such as TNF-a. However, leptin did not directly affect the Nrf2-Keap pathway, which controls oxidative stress. Furthermore, an increase in BMI did not impact esophageal mucosal defense function. It is suggested that the exacerbation of esophageal ulcers due to obesity may promote the development of Barrett's esophagus and its involvement in esophageal adenocarcinoma, but it may not be associated with a decrease in esophageal defense function.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

近年、欧米では肥満率の急速な増加と共に食道腺癌（EAC）とその発生母地でありGERDが引き起こすバレット食道が増加している。本邦でも肥満が増加傾向であるが、EACは微増に留まっている。今後、本邦において急激な増加に転じる可能性が危惧されているが、GERD治療に用いられるPPIやH2阻害薬などの酸分泌抑制薬は普及したもののEAC抑制はなされていない。本研究は肥満の抑制が本邦におけるEAC増加を予防する上で重要であることに加え、肥満ホルモンによる炎症促進を抑制する治療薬の開発が必要であることを示すものである。