Obesity-associated up-regulation of lipocalin 2 protects gastric mucosa cells from apoptotic cell death by reducing endoplasmic reticulum stress.
Xin WenBin SuMingming GaoJiaqi ChenDonglei ZhouHui YouNannan LiShuaikang ChangXiaoyun ChengChunhua QianJingyang GaoPeng YangShen QuLe BuPublished in: Cell death & disease (2021)
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.
Keyphrases
- endoplasmic reticulum stress
- induced apoptosis
- cell death
- weight loss
- metabolic syndrome
- cell cycle arrest
- type diabetes
- high fat diet induced
- insulin resistance
- adipose tissue
- oxidative stress
- signaling pathway
- weight gain
- bariatric surgery
- cell proliferation
- end stage renal disease
- obese patients
- newly diagnosed
- physical activity
- working memory
- long non coding rna
- gene expression
- pi k akt
- skeletal muscle
- prognostic factors