A recent study published in Cell Metabolism identifies a new mechanism by which obesity affects pituitary function through disrupting the unfolded protein response (UPR), and the resultant endocrine defects leading to maladptive hepatic UPR and progression of nonalcoholic fatty liver disease (NAFLD, also known as metabolic dysfunction-associated steatotic liver disease).

Hormone secretion from the pituitary is carried out by specialised secretory cells, which require a functional endoplasmic reticulum (ER) for their endocrine output. Upon stress, cells initiate the UPR to regulate ER stress and restore ER homeostasis. An impaired UPR in secretory endocrine cells can result in reduced hormone secretion, as occurs in insulin-secreting pancreatic β-cells during diabetes mellitus. “However, to our best knowledge, no published studies have characterized the pituitary UPR functional significance in the context of obesity,” says Yang. Thus, the researchers set out to address these knowledge gaps, using a variety of approaches to study human tissue and genetic mouse models.