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Brown fat was hypertrophic and contained fat-laden cells resembling immature white fat. Levels of mRNA encoding adipocyte differentiation markers (C\/EBP\u03b1, PPAR\u03b3, adipsin, leptin, <jats:italic>UCP1<\/jats:italic>) were reduced, but levels of Pref-1 and TNF\u03b1 were increased. (2) Marked insulin resistance with 60-fold elevation in plasma insulin. (3) Diabetes mellitus with elevated blood glucose (&gt;300 mg\/dl) that failed to decline when insulin was injected. (4) Fatty liver from birth and elevated plasma triglyceride levels later in life. These mice exhibit many of the features of congenital generalized lipodystrophy (CGL), an autosomal recessive disorder in humans.<\/jats:p>","DOI":"10.1101\/gad.12.20.3182","type":"journal-article","created":{"date-parts":[[2008,2,20]],"date-time":"2008-02-20T22:52:17Z","timestamp":1203547937000},"page":"3182-3194","source":"Crossref","is-referenced-by-count":666,"title":["Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy"],"prefix":"10.1101","volume":"12","author":[{"given":"Iichiro","family":"Shimomura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert E.","family":"Hammer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Ikemoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriy","family":"Bashmakov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"Goldstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[1998,10,15]]},"reference":[{"key":"2021111418573200000_12.20.3182.1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0167-4889(94)90261-5","article-title":"Cloning of the mouse insulin receptor substrate-1 (IRS-1) gene and complete sequence of mouse IRS-1.","volume":"1221","author":"Araki","year":"1994","journal-title":"Biochim. 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