Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 24, Pages 14457-14462Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2336090100
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Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPARgamma2-specific exon B, resulting in a white adipose tissue knockdown of PPARgamma. Although homozygous (PPARgamma(hyp/hyp)) mice are born with similar weight as the WT mice, the PPARgamma(hyp/hyp) animals become growth retarded and develop severe lipodystrophy and hyperlipidemia. Almost half of these PPARgamma(hyp/hyp) mice die before adulthood, whereas the surviving PPARgamma(hyp/hyp) animals overcome the growth retardation, yet remain lipodystrophic. In contrast to most lipodystrophic models, the adult PPARgamma(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 PPARgamma(hyp/hyp) mice unequivocally demonstrate that PPARgamma 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.
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