{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T16:33:47Z","timestamp":1773419627311,"version":"3.50.1"},"reference-count":27,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2016,9,22]],"date-time":"2016-09-22T00:00:00Z","timestamp":1474502400000},"content-version":"vor","delay-in-days":79,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Japanese Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Japanese Ministry of Health, Labor and Welfare"},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,10,1]]},"abstract":"<jats:p>Agonist-induced activation of peroxisome proliferator\u2013activated receptor-\u03b3 (PPAR\u03b3) stimulates adipocyte differentiation and insulin sensitivity. Patients with heterozygous PPAR\u03b3 dominant-negative mutation develop partial lipodystrophy and insulin resistance. Inconsistent with this evidence in humans, it was reported that heterozygous PPAR\u03b3 knockout mice have increased insulin sensitivity and that mice with heterozygous PPAR\u03b3 dominant-negative mutation have normal insulin sensitivity and improved glucose tolerance. In the context of the interspecies intranslatability of PPAR\u03b3-related findings, we generated a PPAR\u03b3 mutant rat with a loss-of-function mutation (Ppargmkyo) without dominant-negative activity by using the ENU (N-ethyl-N-nitrosourea) mutagenesis method. Heterozygous Ppargmkyo\/+ rats showed reduced fat mass with adipocyte hypertrophy and insulin resistance, which were highly predictable from known actions of PPAR\u03b3 agonists and phenotypes of patients with the PPAR\u03b3 mutation. This report is the first in our knowledge to clearly demonstrate that both alleles of PPAR\u03b3 are required for normal adipocyte development and insulin sensitivity in vivo. Furthermore, the study indicates that PPAR\u03b3 regulates mainly adipocyte number rather than adipocyte size in vivo. The choice of appropriate species as experimental models is critical, especially for the study of PPAR\u03b3.<\/jats:p>","DOI":"10.2337\/db15-1422","type":"journal-article","created":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T02:28:43Z","timestamp":1467772123000},"page":"2954-2965","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":24,"title":["Fat Mass Reduction With Adipocyte Hypertrophy and Insulin Resistance in Heterozygous PPAR\u03b3 Mutant Rats"],"prefix":"10.2337","volume":"65","author":[{"given":"Valentino","family":"Gumbilai","sequence":"first","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Ebihara","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, 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