{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:19:22Z","timestamp":1791411562941,"version":"4.3.3"},"reference-count":51,"publisher":"American Diabetes Association","issue":"12","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:p>OBJECTIVE\u2014White adipose tissue is a critical regulator of whole-body glucose metabolism. Preadipocyte factor-1 (Pref-1) is a secreted protein that inhibits adipocyte differentiation, both in vitro and in vivo. In this study, we have investigated the effects of Pref-1 overexpression on whole-body glucose homeostasis and its contribution to the development of insulin resistance.<\/jats:p><jats:p>RESEARCH DESIGN AND METHODS\u2014To gain insight into the role of Pref-1 on the onset of insulin resistance and type 2 diabetes, we measured body composition and whole-body insulin-stimulated glucose metabolism during a hyperinsulinemic-euglycemic clamp in Pref-1 transgenic and wild-type control mice fed a high-fat diet.<\/jats:p><jats:p>RESULTS\u2014Mice overexpressing Pref-1 were resistant to high-fat diet\u2013induced obesity, as reflected by a marked reduction in adipose tissue mass. However, Pref-1\u2013overexpressing mice were severely insulin resistant, mainly because of a reduction in insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. The aggravated insulin resistance was associated with impaired insulin signaling and increased diacylglycerol content in skeletal muscle.<\/jats:p><jats:p>CONCLUSIONS\u2014Mice overexpressing Pref-1 are insulin resistant despite being protected from diet-induced obesity and may provide a new rodent model for the study of lipodystrophic disorders.<\/jats:p>","DOI":"10.2337\/db07-1739","type":"journal-article","created":{"date-parts":[[2008,10,4]],"date-time":"2008-10-04T00:54:48Z","timestamp":1223081688000},"page":"3258-3266","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":81,"title":["Resistance to High-Fat Diet\u2013Induced Obesity but Exacerbated Insulin Resistance in Mice Overexpressing Preadipocyte Factor-1 (Pref-1)"],"prefix":"10.2337","volume":"57","author":[{"given":"Josep A.","family":"Villena","sequence":"first","affiliation":[{"name":"Department of Nutritional Science and Toxicology, University of California, Berkeley, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheol Soo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science and Toxicology, University of California, Berkeley, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheene","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Bum","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary","family":"Cline","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald I.","family":"Shulman","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Department of Cellular and Molecular Physiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hei Sook","family":"Sul","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science and Toxicology, University of California, Berkeley, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207453765200_R1","doi-asserted-by":"crossref","unstructured":"Smyth S, Heron A: Diabetes and obesity: the twin epidemics. 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