{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T14:46:47Z","timestamp":1769266007166,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,7,6]],"date-time":"2006-07-06T00:00:00Z","timestamp":1152144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2007,5]]},"abstract":"<jats:p>\n                    <jats:bold>Aim:\u2002<\/jats:bold>\n                    The aim of this study was to examine the mechanism by which a novel non\u2010thiazolidinedione (TZD) peroxisome proliferator\u2010activated receptor (PPAR) \u03b3 agonist, FK614, ameliorates insulin resistance in Zucker fatty rats.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:\u2002<\/jats:bold>\n                    FK614 (1, 3.2 or 10 mg\/kg) and a TZD PPAR\u03b3 agonist, pioglitazone (1, 3.2 or 10 mg\/kg), were orally administered to Zucker fatty rats (genetically obese and insulin resistant) once a day for 14 days, and an oral glucose tolerance test was performed. The expression levels of various genes in the white adipose tissue (WAT) of Zucker fatty rats treated with FK614 (3.2 mg\/kg), pioglitazone (10 mg\/kg) and another TZD PPAR\u03b3 agonist, rosiglitazone (3.2 mg\/kg), were determined using a real\u2010time reverse transcription\u2013polymerase chain reaction method. Morphometric analysis of the WAT of Zucker fatty rats treated with FK614 (3.2 mg\/kg) and pioglitazone (10 mg\/kg) was performed. Glucose transport activity in the isolated soleus muscle of FK614\u2010treated Zucker fatty rats was also investigated.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:\u2002<\/jats:bold>\n                    FK614 and pioglitazone both improved glucose tolerance in Zucker fatty rats. FK614 significantly increased the expression levels of acyl CoA oxidase, a PPAR\u2010responsive gene, and adipocyte fatty acid\u2013binding protein (aP2), an adipocyte differentiation marker gene, in epididymal WAT. It also significantly decreased the level of gene expression of tumour necrosis factor\u2010\u03b1, an insulin resistance\u2013inducing factor in retroperitoneal WAT, as did pioglitazone and rosiglitazone. FK614 and pioglitazone both significantly increased the total number of adipocytes and decreased their average size in WAT, mainly by increasing the number of small adipocytes. Additionally, administration of FK614 to Zucker fatty rats enhanced insulin sensitivity for glucose uptake in the soleus muscle.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:\u2002<\/jats:bold>\n                    This study suggests the possibility that FK614 induces adipocyte differentiation in Zucker fatty rats by stimulating PPAR\u03b3\n                    <jats:italic>in vivo<\/jats:italic>\n                    , thereby changing the character of WAT and improving insulin sensitivity throughout the body.\n                  <\/jats:p>","DOI":"10.1111\/j.1463-1326.2006.00619.x","type":"journal-article","created":{"date-parts":[[2006,7,6]],"date-time":"2006-07-06T06:48:01Z","timestamp":1152168481000},"page":"369-378","source":"Crossref","is-referenced-by-count":29,"title":["Mechanism by which a novel non\u2010thiazolidinedione peroxisome proliferator\u2010activated receptor \u03b3 agonist, FK614, ameliorates insulin resistance in Zucker fatty rats"],"prefix":"10.1111","volume":"9","author":[{"given":"H.","family":"Minoura","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Takeshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Hirosumi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Takakura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Kawamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Seki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Manda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Mutoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2006,7,6]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2004.6.850"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.47.4.507"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.46.9.1393"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1235"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.04.038"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2005.05.042"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)91645-S"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/358771a0"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0050578"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00918.x"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.3.783"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81654-2"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.10.1224"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1228-z"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801497"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2005-0005"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(78)80013-4"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1860525"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118703"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119424"},{"key":"e_1_2_5_22_2","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.2337\/diab.46.8.1319","article-title":"Tissue 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