Xin Wen1,2, Bin Su1,2, Mingming Gao3, Jiaqi Chen1,4, Donglei Zhou5, Hui You1,2, Nannan Li1,2, Shuaikang Chang6, Xiaoyun Cheng1,2, Chunhua Qian1,2, Jingyang Gao1,2, Peng Yang1,2, Shen Qu7,8, Le Bu9,10. 1. Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. 2. National Metabolic Management Center, Shanghai, 200072, China. 3. Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, 250 West Green Street, Athens, GA, 30602, USA. 4. Department of Endocrinology and Metabolism, Suzhou Municipal Hospital, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China. 5. Department of Gastrointestinal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. 6. Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. 7. Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. qushencn@hotmail.com. 8. National Metabolic Management Center, Shanghai, 200072, China. qushencn@hotmail.com. 9. Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China. geyingjun@hotmail.com. 10. National Metabolic Management Center, Shanghai, 200072, China. geyingjun@hotmail.com.
Abstract
Gastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.
Gastric mucosal injury is a less well known complication of pan class="Disease">obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.
Authors: Maria Elizabeth de Sousa Rodrigues; Mandakh Bekhbat; Madelyn C Houser; Jianjun Chang; Douglas I Walker; Dean P Jones; Claudia M P Oller do Nascimento; Christopher J Barnum; Malú G Tansey Journal: Brain Behav Immun Date: 2016-09-02 Impact factor: 7.217