{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T02:15:43Z","timestamp":1791771343890,"version":"4.3.4"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,1,2]],"date-time":"2019-01-02T00:00:00Z","timestamp":1546387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2RO1\u2010HD045965"],"award-info":[{"award-number":["2RO1\u2010HD045965"]}],"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":["R01\u2010HD075285"],"award-info":[{"award-number":["R01\u2010HD075285"]}],"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":["R01\u2010HD093729"],"award-info":[{"award-number":["R01\u2010HD093729"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["TL1\u2010TR001081"],"award-info":[{"award-number":["TL1\u2010TR001081"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["R01 HD093729"],"award-info":[{"award-number":["R01 HD093729"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Wild\u2010type mice and mice with hepatocyte\u2010specific or whole\u2010body deletions of perilipin\u20102 (Plin2) were used to define hepatocyte and extra\u2010hepatocyte effects of altered cellular lipid storage on obesity and non\u2010alcoholic fatty liver disease (NAFLD) pathophysiology in a Western\u2010diet (WD) model of these disorders.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Extra\u2010hepatocyte actions of Plin2 are responsible for obesity, adipose inflammation and glucose clearance abnormalities in WD\u2010fed mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hepatocyte and extra\u2010hepatic actions of Plin2 mediate fatty liver formation in WD\u2010fed mice through distinct mechanisms.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hepatocyte\u2010specific actions of Plin2 are primary mediators of immune cell infiltration and fibrotic injury in livers of obese mice.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) is an obesity\u2010 and insulin resistance\u2010related metabolic disorder with progressive pathology. Perilipin\u20102 (Plin2), a ubiquitously expressed cytoplasmic lipid droplet scaffolding protein, is hypothesized to contribute to NAFLD in humans and rodent models through effects on cellular lipid metabolism. In this study, we delineate hepatocyte\u2010specific and extra\u2010hepatocyte Plin2 mechanisms regulating the effects of obesity and insulin resistance on NAFLD pathophysiology in mice fed an obesogenic Western\u2010style diet (WD). Total Plin2 deletion (Plin2\u2010Null) fully protected WD\u2010fed mice from obesity, insulin resistance, adipose inflammation, steatohepatitis (NASH) and liver fibrosis found in WT animals. Hepatocyte\u2010specific Plin2 deletion (Plin2\u2010HepKO) largely protected against NASH and fibrosis and partially protected against steatosis in WD\u2010fed animals, but it did not protect against obesity, insulin resistance, or adipose inflammation. Significantly, total or hepatocyte\u2010specific Plin2 deletion impaired WD\u2010induced monocyte recruitment and pro\u2010inflammatory macrophage polarization found in livers of WT mice. Analyses of the molecular and cellular processes mediating steatosis, inflammation and fibrosis identified differences in total and hepatocyte\u2010specific actions of Plin2 on the mechanisms promoting NAFLD pathophysiology. Our results demonstrate that hepatocyte\u2010specific actions of Plin2 are central to the initiation and pathological progression of NAFLD in obese and insulin\u2010resistant mice through effects on immune cell recruitment and fibrogenesis. Conversely, extra\u2010hepatocyte Plin2 actions promote NAFLD pathophysiology through effects on obesity, inflammation and insulin resistance. Our findings provide new insight into hepatocyte and extra\u2010hepatocyte mechanisms underlying NAFLD development and progression.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp277140","type":"journal-article","created":{"date-parts":[[2018,12,8]],"date-time":"2018-12-08T13:43:40Z","timestamp":1544276620000},"page":"1565-1584","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Perilipin\u20102 promotes obesity and progressive fatty liver disease in mice through mechanistically distinct hepatocyte and extra\u2010hepatocyte actions"],"prefix":"10.1113","volume":"597","author":[{"given":"David J.","family":"Orlicky","sequence":"first","affiliation":[{"name":"Department of Pathology University of Colorado School of Medicine  Aurora CO USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew E.","family":"Libby","sequence":"additional","affiliation":[{"name":"Graduate Program in Integrated Physiology 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