{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T13:35:02Z","timestamp":1789997702648,"version":"4.0.1"},"reference-count":50,"publisher":"American Society for Clinical Investigation","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4,20]]},"abstract":"<jats:p>Nonalcoholic fatty liver disease (NAFLD), characterized by an excess accumulation of hepatic triglycerides, is a growing health epidemic. While ER stress in the liver has been implicated in the development of NAFLD, the role of brain ER stress \u2014 which is emerging as a key contributor to a number of chronic diseases including obesity \u2014 in NAFLD remains unclear. These studies reveal that chemical induction of ER stress in the brain caused hepatomegaly and hepatic steatosis in mice. Conversely, pharmacological reductions in brain ER stress in diet-induced obese mice rescued NAFLD independent of body weight, food intake, and adiposity. Evaluation of brain regions involved revealed robust activation of ER stress biomarkers and ER ultrastructural abnormalities in the circumventricular subfornical organ (SFO), a nucleus situated outside of the blood-brain-barrier, in response to high-fat diet. Targeted reductions in SFO-ER stress in obese mice via SFO-specific supplementation of the ER chaperone 78-kDa glucose\u2013regulated protein ameliorated hepatomegaly and hepatic steatosis without altering body weight, food intake, adiposity, or obesity-induced hypertension. Overall, these findings indicate a novel role for brain ER stress, notably within the SFO, in the pathogenesis of NAFLD.<\/jats:p>","DOI":"10.1172\/jci.insight.90170","type":"journal-article","created":{"date-parts":[[2017,4,19]],"date-time":"2017-04-19T11:00:56Z","timestamp":1492599656000},"source":"Crossref","is-referenced-by-count":25,"title":["Obesity-induced hepatic steatosis is mediated by endoplasmic reticulum stress in the subfornical organ of the brain"],"prefix":"10.1172","volume":"2","author":[{"given":"Julie A.","family":"Horwath","sequence":"first","affiliation":[{"name":"Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA."},{"name":"Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chansol","family":"Hurr","sequence":"additional","affiliation":[{"name":"Pharmacology and Physiology, School of Medicine and Health Sciences, The 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