{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T09:07:51Z","timestamp":1789895271456,"version":"4.0.1"},"reference-count":53,"publisher":"The Endocrine Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Insulin is a potent adipogenic hormone that triggers the induction of a series of transcription factors and specific proteins governing the differentiation of preadipocytes into mature adipocytes. Here we report that ubiquitin carboxyl-terminal hydrolase (UCH)-L3, a deubiquitinating enzyme, promotes insulin signaling and adipogenesis. Uchl3\u2212\/\u2212 mice had less visceral white adipose tissue compared with wild-type mice. In vitro adipogenesis experiments revealed that mouse embryonic fibroblasts (MEFs) and preadipocytes from Uchl3\u2212\/\u2212 mice had impaired ability to differentiate into mature adipocytes than those from wild-type mice. This difference was diminished by removing insulin from the medium. RT-PCR analysis showed that insulin-regulated expression of srebp1c, fas, glut4, and adiponectin is impaired in Uchl3\u2212\/\u2212 cells. The phosphorylation of insulin\/IGF-I receptor, Akt, glycogen synthase kinase-3\u03b2, and FoxO1 was decreased in Uchl3\u2212\/\u2212 MEFs treated with insulin. Moreover, ectopic expression of wild-type UCH-L3 restored the phosphorylation of insulin\/IGF-I receptor and adipocyte differentiation in Uchl3\u2212\/\u2212 MEFs. In contrast, hydrolase activity-deficient UCH-L3 did not enhance insulin signaling and the expression of glut4, fabp4, and adiponectin, resulting in impaired formation of large lipid droplets. These results suggest that UCH-L3 promotes adipogenesis by enhancing insulin signaling in a hydrolase activity-dependent manner.<\/jats:p>","DOI":"10.1210\/en.2009-0332","type":"journal-article","created":{"date-parts":[[2009,10,17]],"date-time":"2009-10-17T01:09:17Z","timestamp":1255741757000},"page":"5230-5239","source":"Crossref","is-referenced-by-count":34,"title":["Ubiquitin Carboxyl-Terminal Hydrolase L3 Promotes Insulin Signaling and Adipogenesis"],"prefix":"10.1210","volume":"150","author":[{"given":"Mari","family":"Suzuki","sequence":"first","affiliation":[{"name":"Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rieko","family":"Setsuie","sequence":"first","affiliation":[{"name":"Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiji","family":"Wada","sequence":"first","affiliation":[{"name":"Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2009,10,16]]},"reference":[{"key":"2020071612415969500_R1","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.arcmed.2008.09.005","article-title":"White adipose tissue as endocrine organ and its role in obesity.","volume":"39","author":"Va\u0301zquez-Vela","year":"2008","journal-title":"Arch Med Res"},{"key":"2020071612415969500_R2","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/oxfordjournals.aje.a009158","article-title":"Body fat distribution and risk of non-insulin-dependent diabetes mellitus in women. 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