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Publication : Resistance to high-fat diet-induced obesity but exacerbated insulin resistance in mice overexpressing preadipocyte factor-1 (Pref-1): a new model of partial lipodystrophy.

First Author  Villena JA Year  2008
Journal  Diabetes Volume  57
Issue  12 Pages  3258-66
PubMed ID  18835937 Mgi Jnum  J:143301
Mgi Id  MGI:3826337 Doi  10.2337/db07-1739
Citation  Villena JA, et al. (2008) Resistance to high-fat diet-induced obesity but exacerbated insulin resistance in mice overexpressing preadipocyte factor-1 (Pref-1): a new model of partial lipodystrophy. Diabetes 57(12):3258-66
abstractText  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.
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