Obesity-associated up-regulation of lipocalin 2 protects gastric mucosa cells from apoptotic cell death by reducing endoplasmic reticulum stress

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.

FXR controls duodenogastric reflux-induced gastric inflammation through negatively regulating ER stress-associated TNXIP/NLPR3 inflammasome

“… 48 Various pathological signals stimulated by obesity or ethanol in the gastric mucosa can activate the UPR in the ER. 49 , 50 The ER stress-activated TXNIP/NLRP3 inflammasome contributes to gastric mucosal injury. 39 GRP78 is an ER-specific chaperone involved in the UPR.…”

Interaction between mucus layer and gut microbiota in non-alcoholic fatty liver disease: Soil and seeds

“…Oxidative stress and inflammatory responses contribute to gastric mucus injury in obese patients, with TNF-α and IL-6 expression showing significant upregulation. [ 96 ] Interestingly, mucus layer defects are associated with obesity, with obese mice exhibiting greater mucus permeability and a decreased mucus growth rate compared to lean mice, while if co-housing the obese and lean mice, the intestinal permeability and mucosal growth rate of obese mice can be restored to some extent. Mucus growth rate in mice suggests that altered gut microbiota structure in obese mice may be responsible for obesity-related mucosal defects.…”

Lipocalin 2—A bone‐derived anorexigenic and β‐cell promoting signal: From mice to humans

“…Moreover, LCN2 −/− mice also exhibit heightened susceptibility to hepatic damage consequent to a high‐fructose diet 36 . Moreover, LCN2 has antiapoptotic cell death effect by mitigating endoplasmic reticulum (ER) stress, 37 and LCN2 silencing renders liver parenchymal cells more susceptible to ER stress resulting from the activation of nuclear factor‐κB and c‐Jun N‐terminal kinase (JNK) pathways 38 . This cascade of events is acknowledged as a contributing factor to the development of hepatic steatosis 39 .…”