期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：29
页码：10703-10708
DOI：10.1073/pnas.0403652101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) is a nuclear receptor that plays a pivotal role in obesity and diabetes. PPAR{gamma} has two isoforms, PPAR{gamma}1 and PPAR{gamma}2. We investigated the functional differences between PPAR{gamma}1 and PPAR{gamma}2 by selectively disrupting PPAR{gamma}2 in mice. In contrast to the embryonic lethality of PPAR{gamma}-deficient mice, PPAR{gamma}2-/- mice survived. Although normal development was identified in other tissues we examined, PPAR{gamma}2-/- mice exhibited an overall reduction in white adipose tissue, less lipid accumulation, and decreased expression of adipogenic genes in adipose tissue. In addition, insulin sensitivity was impaired in male PPAR{gamma}2-/- mice, with dramatically decreased expression of insulin receptor substrate 1 and glucose transporter 4 in the skeletal muscle, but thiazolidinediones were able to normalize this insulin resistance. Consistent with in vivo data, PPAR{gamma}2-/- mouse embryonic fibroblasts showed a dramatically reduced capacity for adipogenesis in vitro compared with wild-type mouse embryonic fibroblasts. Taken together, our data demonstrate that PPAR{gamma}2 deficiency impairs the development of adipose tissue and insulin sensitivity. PPAR{gamma}2-/- mice may provide a tool to study the role of PPAR{gamma}2 in obesity and diabetes.
