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. Overall design: Livers were collected from IRE1 PKO vs IREfl HFD male mice (4 hrs feeding following a 16-hrs fasting).