Obesity Disrupts the Pituitary-Hepatic UPR Communication Leading to NAFLD Progression (liver bulk RNA seq)

Obesity alters circulating levels of pituitary hormones that govern hepatic immune-metabolic homeostasis, and dysregulation of which leads to NAFLD. Here, using diet induced obese mouse and IRE1PKO mice, we uncovered an blunted unfolded protein response (UPR) but elevated inflammatory signatures in pituitary glands of obese mice. Mechanistically, we demonstrated that the pituitary IRE1alpha-XBP1 UPR branch is essential for protecting against pituitary endocrine defects and NAFLD progression in obesity. Livers were collected from IRE1 PKO vs IREfl HFD male mice (4 hrs feeding following a 16-hrs fasting).

肥胖可改变循环中调控肝脏免疫代谢稳态的垂体激素水平，此类激素的失调会引发非酒精性脂肪性肝病（NAFLD）。本研究以饮食诱导肥胖小鼠及IRE1PKO小鼠为模型，发现肥胖小鼠垂体组织内的未折叠蛋白反应（UPR）受到抑制，而炎症特征显著增强。机制层面，我们证实垂体的IRE1α-XBP1 UPR通路对于抵御肥胖诱导的垂体内分泌缺陷及非酒精性脂肪性肝病（NAFLD）进展至关重要。本研究的肝脏样本采集自IRE1PKO与IRE1fl高脂饮食（HFD）雄性小鼠，采样前小鼠经16小时禁食后再喂食4小时。