{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T16:10:05Z","timestamp":1777047005015,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,12,15]],"date-time":"2016-12-15T00:00:00Z","timestamp":1481760000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Dipeptidyl peptidase\u20104 inhibitors are used for treatment of patients with type 2 diabetes. In addition to glycemic control, these agents showed beneficial effects on lipid metabolism in clinical trials. However, the mechanism underlying the lipid\u2010lowering effect of dipeptidyl peptidase\u20104 inhibitors remains unclear. Here, we investigated the lipid\u2010lowering efficacy of anagliptin in a hyperlipidemic animal model, and examined the mechanism of action.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>Male low\u2010density lipoprotein receptor\u2010deficient mice were administered 0.3% anagliptin in their diet. Plasma lipid levels were assayed and lipoprotein profile was analyzed using high\u2010performance liquid chromatography. Hepatic gene expression was examined by deoxyribonucleic acid microarray and quantitative polymerase chain reaction analyses. Sterol regulatory element\u2010binding protein transactivation assay was carried out <jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Anagliptin treatment significantly decreased the plasma total cholesterol (14% reduction, <jats:italic>P<\/jats:italic> &lt; 0.01) and triglyceride levels (27% reduction, <jats:italic>P<\/jats:italic> &lt; 0.01). Both low\u2010density lipoprotein cholesterol and very low\u2010density lipoprotein cholesterol were also decreased significantly by anagliptin treatment. Sterol regulatory element\u2010binding protein\u20102 messenger ribonucleic acid expression level was significantly decreased at night in anagliptin\u2010treated mice (15% reduction, <jats:italic>P<\/jats:italic> &lt; 0.05). Anagliptin significantly suppressed sterol regulatory element\u2010binding protein activity in HepG2 cells (21% decrease, <jats:italic>P<\/jats:italic> &lt; 0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results presented here showed that the dipeptidyl peptidase\u20104 inhibitor, anagliptin, exhibited a lipid\u2010lowering effect in a hyperlipidemic animal model, and suggested that the downregulation of hepatic lipid synthesis was involved in the effect. Anagliptin might have beneficial effects on lipid metabolism in addition to a glucose\u2010lowering effect.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.12593","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T19:50:20Z","timestamp":1479153020000},"page":"155-160","source":"Crossref","is-referenced-by-count":26,"title":["Mechanism of lipid\u2010lowering action of the dipeptidyl peptidase\u20104 inhibitor, anagliptin, in low\u2010density lipoprotein receptor\u2010deficient mice"],"prefix":"10.1111","volume":"8","author":[{"given":"Wataru","family":"Yano","sequence":"first","affiliation":[{"name":"Tokyo New Drug Research Laboratories Kowa Company, Ltd Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noriyuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Tokyo New Drug Research Laboratories Kowa Company, Ltd Tokyo 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