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- Title
Resistance to High-Fat Diet-Induced Obesity but Exacerbated Insulin Resistance in Mice Overexpressing Preadipocyte Factor-1 (Pref-1).
- Authors
Villena, Josep A.; Cheol Soo Choi; Yuhui Wang; Kim, Sheene; Yu-Jin Hwang; Young-Bum Kim; Cline, Gary; Shulman, Gerald I.; Hei Sook Sul
- Abstract
OBJECTIVE--White 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. RESEARCH DESIGN AND METHODS--To 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. RESULTS--Mice overexpressing Pref-1 were resistant to high-fat diet-induced obesity, as reflected by a marked reduction in adipose tissue mass. However, Pref-1-overexpressing 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. CONCLUSIONS--Mice 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. Diabetes 57:3258-3266, 2008
- Subjects
FAT cells; INSULIN resistance; OBESITY; TYPE 2 diabetes; ADIPOSE tissue diseases; DYSTROPHY
- Publication
Diabetes, 2008, Vol 57, Issue 12, p3258
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db07-1739