Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPARγ hypomorphic mice

Hana Koutnikova, Terrie Anne Cock, Mitsuhiro Watanabe, Sander M. Houten, Marie France Champy, Andrée Dierich, Johan Auwerx

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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor, which controls adipocyte differentiation. We targeted with homologous recombination the PPARγ2-specific exon B, resulting in a white adipose tissue knockdown of PPARγ. Although homozygous (PPARγ hyp/hyp) mice are born with similar weight as the WT mice, the PPARγhyp/hyp animals become growth retarded and develop severe lipodystrophy and hyperlipidemia. Almost half of these PPARγ hyp/hyp mice die before adulthood, whereas the surviving PPARγhyp/hyp animals overcome the growth retardation, yet remain lipodystrophic. In contrast to most lipodystrophic models, the adult PPARγhyp/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 PPARγhyp/hyp mice unequivocally demonstrate that PPARγ 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.

Original languageEnglish
Pages (from-to)14457-14462
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue numberSUPPL. 2
DOIs
Publication statusPublished - 2003 Nov 25

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