{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:47:59Z","timestamp":1791082079344,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,10,27]],"date-time":"2013-10-27T00:00:00Z","timestamp":1382832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Lipids"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated whether: (1) liver X receptor (LXR)\u2010driven induction of high\u2010density lipoprotein cholesterol (HDL\u2010C) and other LXR\u2010mediated effects on cholesterol metabolism depend on intestinal cholesterol absorption; and (2) combined treatment with the LXR agonist GW3965 and the cholesterol absorption inhibitor ezetimibe results in synergistic effects on cholesterol metabolism that could be beneficial for treatment of atherosclerosis. Mice were fed 0.2 % cholesterol and treated with GW3965+ezetimibe, GW3965 or ezetimibe. GW3965+ezetimibe treatment elevated serum HDL\u2010C and Apolipoprotein (Apo) AI, effectively reduced the intestinal cholesterol absorption and increased the excretion of faecal neutral sterols. No changes in intestinal ATP\u2010binding cassette (ABC) A1 or ABCG5 protein expression were observed, despite increased mRNA expression, while hepatic ABCA1 was slightly reduced. The combined treatment caused a pronounced down\u2010regulation of intestinal Niemann\u2013Pick C1\u2010like 1 (NPC1L1) and reduced hepatic and intestinal cholesterol levels. GW3965 did not affect the intestinal cholesterol absorption, but increased serum HDL\u2010C and ApoAI levels. GW3965 also increased <jats:italic>Apoa1<\/jats:italic> mRNA levels in primary mouse hepatocytes and HEPA1\u20106 cells. Ezetimibe reduced the intestinal cholesterol absorption, ABCA1 and ABCG5, but did not affect the serum HDL\u2010C or ApoAI levels. Thus, the LXR\u2010driven induction of HDL\u2010C and ApoAI was independent of the intestinal cholesterol absorption and increased expression of intestinal or hepatic ABCA1 was not required. Inhibited influx of cholesterol via NPC1L1 and\/or low levels of intracellular cholesterol prevented post\u2010transcriptional expression of intestinal ABCA1 and ABCG5, despite increased mRNA levels. Combined LXR activation and blocked intestinal cholesterol absorption induced effective faecal elimination of cholesterol.<\/jats:p>","DOI":"10.1007\/s11745-013-3853-8","type":"journal-article","created":{"date-parts":[[2013,10,26]],"date-time":"2013-10-26T01:57:20Z","timestamp":1382752640000},"page":"71-83","source":"Crossref","is-referenced-by-count":20,"title":["LXR Driven Induction of HDL\u2010Cholesterol is Independent of Intestinal Cholesterol Absorption and ABCA1 Protein Expression"],"prefix":"10.1002","volume":"49","author":[{"given":"Kristina","family":"Kannisto","sequence":"first","affiliation":[{"name":"Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet Karolinska University Hospital Huddinge Stockholm 141 86 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats","family":"G\u00e5fvels","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet Karolinska University Hospital Huddinge Stockholm 141 86 Sweden"},{"name":"Division of Clinical Chemistry, Department of Laboratory Medicine Lund University Lund 221 00 Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao\u2010Yan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet Karolinska University Hospital Huddinge Stockholm 141 86 Sweden"},{"name":"Department of Surgery, Shanghai Institute of Digestive Surgery Shanghai Jiaotong University School of Medicine Luwan Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Sl\u00e4tis","sequence":"additional","affiliation":[{"name":"Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet Karolinska University Hospital Huddinge Stockholm 141 86 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