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

H Koutnikova, TA Cock, M Watanabe… - Proceedings of the …, 2003 - National Acad Sciences
H Koutnikova, TA Cock, M Watanabe, SM Houten, MF Champy, A Dierich, J Auwerx
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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
(PPAR γ hyp/hyp) mice are born with similar weight as the WT mice, the PPAR γ hyp/hyp
animals become growth retarded and develop severe lipodystrophy and hyperlipidemia.
Almost half of these PPAR γ hyp/hyp mice die before adulthood, whereas the surviving …
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 (PPARγhyp/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 PPARγhyp/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.
National Acad Sciences