{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:58:47Z","timestamp":1778273927894,"version":"3.51.4"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,1,20]],"date-time":"2020-01-20T00:00:00Z","timestamp":1579478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 108-2320-B-182A-006"],"award-info":[{"award-number":["MOST 108-2320-B-182A-006"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107-2320-B-182A-027"],"award-info":[{"award-number":["MOST 107-2320-B-182A-027"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004606","name":"Chang Gung Medical Foundation","doi-asserted-by":"publisher","award":["CMRPG8G1381"],"award-info":[{"award-number":["CMRPG8G1381"]}],"id":[{"id":"10.13039\/501100004606","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD), the leading cause of chronic liver diseases worldwide, ranges from simple steatosis to steatohepatitis, with the risk for progressive fibrosis or even cirrhosis. While simple steatosis is a relatively benign condition, the buildup of toxic lipid metabolites can induce chronic inflammation, ultimately triggering disease progression. Pigment epithelium-derived factor (PEDF) is a secreted, multifunctional glycoprotein with lipid metabolic activities. PEDF promotes lipolysis through binding to adipose triglyceride lipase (ATGL), a key enzyme for triglyceride breakdown. In the current study, we aimed to delineate how changes in PEDF expression affect hepatic lipid accumulation. Our data revealed that hepatic PEDF was downregulated in a mouse NAFLD model. We further showed that decreased PEDF levels in hepatocytes in vitro resulted in elevated fatty acid uptake and lipid droplet formation, with concomitant upregulation of fatty acid transport proteins CD36 and fatty acid binding protein 1 (FABP1). RNA sequencing analysis of PEDF knocked down hepatocytes revealed an alteration in gene expression profile toward lipid accumulation. Additionally, decreased PEDF promotes mobilization of fatty acids, an observation distinct from blocking ATGL activity. Taken together, our data suggest that hepatic PEDF downregulation causes molecular changes that favor triglyceride accumulation, which may further lead to NAFLD progression.<\/jats:p>","DOI":"10.3390\/nu12010270","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T03:04:43Z","timestamp":1579575883000},"page":"270","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Decreased PEDF Promotes Hepatic Fatty Acid Uptake and Lipid Droplet Formation in the Pathogenesis of NAFLD"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-3130","authenticated-orcid":false,"given":"Kuang-Tzu","family":"Huang","sequence":"first","affiliation":[{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuang-Den","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Wen","family":"Hsu","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Pin","family":"Kung","sequence":"additional","affiliation":[{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Rong","family":"Li","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chien-Chih","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2108-6539","authenticated-orcid":false,"given":"King-Wah","family":"Chiu","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Goto","sequence":"additional","affiliation":[{"name":"Fukuoka Institute of Occupational Health, Fukuoka 815-0081, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao-Long","family":"Chen","sequence":"additional","affiliation":[{"name":"Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases","volume":"67","author":"Chalasani","year":"2018","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/1751-2980.12291","article-title":"Nonalcoholic fatty liver disease\u2014Current status and future directions","volume":"16","author":"Demir","year":"2015","journal-title":"J. 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