Obesity Disrupts the Pituitary-Hepatic UPR Communication Leading to NAFLD Progression (pituitary scRNA 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 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. Pituitaries were collected from WT RD vs HFD, and IRE1 PKO vs IREfl RD male mice (4 hrs feeding following a 16-hrs fasting).