{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:30:56Z","timestamp":1783949456194,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["AHA932522"],"award-info":[{"award-number":["AHA932522"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK117007"],"award-info":[{"award-number":["R01DK117007"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01HL141393"],"award-info":[{"award-number":["R01HL141393"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Nonalcoholic fatty liver disease (NAFLD), characterized by excess liver triglyceride accumulation (hepatic steatosis), leads to an increased risk for cardiometabolic diseases and obesity\u2010related mortality. Emerging evidence points to endoplasmic reticulum (ER) stress in the central nervous system as critical in NAFLD pathogenesis. Here, we tested the contribution of ER stress in a circumventricular organ\u2010hypothalamic circuit in NAFLD development during obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6J male mice were fed a high\u2010fat diet (HFD) or normal chow. A combination of histological, viral tracing, intersectional viral targeting, and <jats:italic>in vivo<\/jats:italic> integrative physiological approaches were used to examine the role of ER stress in subfornical organ to hypothalamic paraventricular nucleus projecting neurons (SFO\u2794PVN) in NAFLD during diet\u2010induced obesity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immunohistochemical analysis revealed marked unfolded protein response activation in the SFO, particularly in excitatory SFO\u2794PVN neurons of HFD\u2010fed animals. Moreover, intersectional viral inhibition of ER stress in SFO\u2794PVN neurons resulted in a reduction in hepatomegaly, hepatic steatosis, and a blunted increase in body weight gain during diet\u2010induced obesity, independent of changes in food intake, substrate partitioning, energy expenditure, and ambulatory activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results indicate that ER stress in an SFO\u2794PVN neural circuit contributes to hepatic steatosis during obesity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/oby.23895","type":"journal-article","created":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T03:35:05Z","timestamp":1696476905000},"page":"59-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Circumventricular organ\u2010hypothalamic circuit endoplasmic reticulum stress drives hepatic steatosis during obesity"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9108-2421","authenticated-orcid":false,"given":"Han Rae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Physiology George Washington University School of Medicine and Health Sciences  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin N.","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Physiology George Washington University School of Medicine and Health Sciences  Washington DC 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