{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:08:15Z","timestamp":1791284895343,"version":"4.1.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,1,28]],"date-time":"2015-01-28T00:00:00Z","timestamp":1422403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2015,1,28]],"date-time":"2015-01-28T00:00:00Z","timestamp":1422403200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31171132"],"award-info":[{"award-number":["31171132"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370958"],"award-info":[{"award-number":["81370958"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81100612"],"award-info":[{"award-number":["81100612"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:p>Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD\u2010binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using <jats:italic toggle=\"yes\">Plin5<\/jats:italic> knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller\u2010sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. <jats:italic toggle=\"yes\">Plin5<\/jats:italic>\u2010deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPAR\u03b1 stimulated by the increased NEFA levels. Meanwhile, <jats:italic toggle=\"yes\">Plin5<\/jats:italic>\u2010deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)\u2010mediated lipolysis by competitively binding to comparative gene identification\u201058 (CGI\u201058) and disrupting the interaction between CGI\u201058 and ATGL. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. (H<jats:sc>epatology<\/jats:sc> 2015;61:870\u2013882)<\/jats:p>","DOI":"10.1002\/hep.27409","type":"journal-article","created":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T15:28:58Z","timestamp":1409585338000},"page":"870-882","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":198,"title":["Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis"],"prefix":"10.1097","volume":"61","author":[{"given":"Chao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathology, Xijing Hospital,Fourth Military Medical University,Xi'an,China"},{"name":"Department of Clinical Diagnosis, Tangdu Hospital,Fourth Military Medical University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanlin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xijing Hospital,Fourth Military Medical 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Clinical Diagnosis, Tangdu Hospital,Fourth Military Medical University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xijing Hospital,Fourth Military Medical University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peizhen","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xijing Hospital,Fourth Military Medical University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiumin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xijing Hospital,Fourth Military Medical University,Xi'an,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Xijing Hospital,Fourth Military Medical 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