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：2003
卷号：100
期号：24
页码：14457-14462
DOI：10.1073/pnas.2336090100
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, which controls adipocyte differentiation. We targeted with homologous recombination the PPAR{gamma}2-specific exon B, resulting in a white adipose tissue knockdown of PPAR{gamma}. Although homozygous (PPAR{gamma}hyp/hyp) mice are born with similar weight as the WT mice, the PPAR{gamma}hyp/hyp animals become growth retarded and develop severe lipodystrophy and hyperlipidemia. Almost half of these PPAR{gamma}hyp/hyp mice die before adulthood, whereas the surviving PPAR{gamma}hyp/hyp animals overcome the growth retardation, yet remain lipodystrophic. In contrast to most lipodystrophic models, the adult PPAR{gamma}hyp/hyp mice only have mild glucose intolerance and do not have a fatty liver. These metabolic consequences of the lipodystrophy are relatively benign because of the induction of a compensatory gene expression program in the muscle that enables efficient oxidation of excess lipids. The PPAR{gamma}hyp/hyp mice unequivocally demonstrate that PPAR{gamma} is the master regulator of adipogenesis in vivo and establish that lipid and glucose homeostasis can be relatively well maintained in the absence of white adipose tissue.
