{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T21:27:07Z","timestamp":1774128427421,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004334","name":"Merck","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004334","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Anacetrapib is an inhibitor of cholesteryl ester transfer protein (CETP) previously under development as a lipid\u2010modifying agent that reduces LDL\u2010cholesterol and increases HDL\u2010cholesterol in hypercholesterolemic patients. Anacetrapib demonstrates a long terminal half\u2010life and accumulates in adipose tissue, which contributes to a long residence time of anacetrapib. Given our previous report that anacetrapib distributes into the lipid droplet of adipose tissue, we sought to understand whether anacetrapib affected adipose function, using a diet\u2010induced obese (DIO) mouse model. Following 20\u00a0weeks of treatment with anacetrapib (100\u00a0mg\/kg\/day), levels of the drug increased to approximately 0.6\u00a0mmol\/L in white adipose tissue. This level of anacetrapib was not associated with any impairment in adipose functionality as evidenced by a lack of any reduction in biomarkers of adipose functionality (plasma adiponectin, leptin, insulin; adipose adiponectin, leptin mRNA). In DIO wild\u2010type (WT) mice treated with anacetrapib for 2\u00a0weeks and then subjected to 30% food restriction during washout to induce weight loss (18%) and fat mass loss (7%), levels of anacetrapib in adipose and plasma were not different between food restricted and ad lib\u2010fed mice. These data indicate that despite deposition and long\u2010term residence of ~0.6\u00a0mmol\/L levels of anacetrapib in adipose tissue, adipose tissue function appears to be unaffected in mice. In addition, these data also indicate that even with severe caloric restriction and acute loss of fat mass, anacetrapib does not appear to be mobilized from the fat depot, thereby solidifying the role of adipose as a long\u2010term storage site of anacetrapib.<\/jats:p>","DOI":"10.1002\/prp2.543","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T11:11:06Z","timestamp":1573816266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Impact of drug distribution into adipose on tissue function: The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib as a test case"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8726-8514","authenticated-orcid":false,"given":"Douglas G.","family":"Johns","sequence":"first","affiliation":[{"name":"Department of Translational Pharmacology Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng\u2010Ping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiometabolic Diseases\/Atherosclerosis Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raymond","family":"Rosa","sequence":"additional","affiliation":[{"name":"Department of Cardiometabolic Diseases\/Atherosclerosis Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Hubert","sequence":"additional","affiliation":[{"name":"Department of Cardiometabolic Diseases\/Atherosclerosis Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suoyu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiometabolic Diseases\/Atherosclerosis Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Bateman","sequence":"additional","affiliation":[{"name":"Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism Merck &amp; Co., Inc. Kenilworth NJ USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert O.","family":"Blaustein","sequence":"additional","affiliation":[{"name":"Department of Clinical Research Merck &amp; Co., Inc. 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