{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:46:42Z","timestamp":1792093602885,"version":"4.4.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T00:00:00Z","timestamp":1467590400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1"},{"start":{"date-parts":[[2016,7,4]],"date-time":"2016-07-04T00:00:00Z","timestamp":1467590400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2016,10,21]]},"abstract":"<jats:p>\n                    There is considerable evidence that both retinoids and retinol\u2010binding protein 4 (RBP4) contribute to the development of liver disease. To understand the basis for this, we generated and studied transgenic mice that express human RBP4 (hRBP4) specifically in adipocytes. When fed a chow diet, these mice show an elevation in adipose total RBP4 (mouse RBP4 + hRBP4) protein levels. However, no significant differences in plasma RBP4 or retinol levels or in hepatic or adipose retinoid (retinol, retinyl ester, and all\u2010\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    \u2010retinoic acid) levels were observed. Strikingly, male adipocyte\u2010specific hRBP4 mice fed a standard chow diet display significantly elevated hepatic triglyceride levels at 3\u20104 months of age compared to matched littermate controls. When mice were fed a high\u2010fat diet, this hepatic phenotype, as well as other metabolic phenotypes (obesity and glucose intolerance), worsened. Because adipocyte\u2010specific hRBP4 mice have increased tumor necrosis factor\u2010\u03b1 and leptin expression and crown\u2010like structures in adipose tissue, our data are consistent with the notion that adipose tissue is experiencing RBP4\u2010induced inflammation that stimulates increased lipolysis within adipocytes. Our data further establish that elevated hepatic triglyceride levels result from increased hepatic uptake of adipose\u2010derived circulating free fatty acids. We obtained no evidence that elevated hepatic triglyceride levels arise from increased hepatic\n                    <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                    lipogenesis, decreased hepatic free fatty acid oxidation, or decreased very\u2010low\u2010density lipoprotein secretion.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    Our investigations establish that RBP4 expressed in adipocytes induces hepatic steatosis arising from primary effects occurring in adipose tissue. (H\n                    <jats:sc>epatology<\/jats:sc>\n                    2016;64:1534\u20101546)\n                  <\/jats:p>","DOI":"10.1002\/hep.28659","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T19:58:00Z","timestamp":1464292680000},"page":"1534-1546","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":97,"title":["Adipocyte\u2010specific overexpression of retinol\u2010binding protein 4 causes hepatic steatosis in mice"],"prefix":"10.1097","volume":"64","author":[{"given":"Seung\u2010Ah","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons,Columbia University,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason J.","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons,Columbia University,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfeng","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons,Columbia University,New York,NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S.","family":"Blaner","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Physicians and Surgeons,Columbia University,New 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