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Submitted on August 27, 2003
Accepted on June 25, 2004
HETEROZYGOUS MICE: Involvement of PPAR in a negative feed-back regulation of growth hormone action
Center for Integrative Genomics, NCCR Frontiers in Genetics, University of Lausanne, CH-1015 Lausanne, Switzerland; Present address: INSERM U449, Faculté de médecine R.T.H. Laennec, rue Guillaume Paradin, 69372 Lyon cedex 08; Centre Médical Universitaire, Département de Physiologie, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland; Present address: Department of Physiology/Neurobiology, University of Basel, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland; Institut de génétique et de biologie moléculaire et cellulaire /CNRS/INSERM/ULP/Collège de France, 67404 Illkirch cedex, CU de Strasbourg, France
* To whom correspondence should be addressed. E-mail: beatrice.desvergne{at}cig.unil.ch.
The peroxisome proliferator-activated receptor 
(PPAR) plays a major role in fat tissue development and physiology. Mutations in the gene encoding this receptor have been associated to disorders in lipid metabolism. A thorough investigation of mice in which one PPAR allele has been mutated reveals that male PPAR heterozygous (PPAR +/-) mice exhibit a reduced body size associated with decreased body weight, reflecting lean mass reduction. This phenotype is reproduced when treating the mice with a PPAR specific antagonist. Monosodium glutamate (MSG) treatment, which induces weight gain and alters body growth in wild-type (wt) mice, further aggravates the growth defect of PPAR +/- mice. The levels of circulating GH (GH) and that of its downstream effector, insulin-like growth factor-I (IGF-I), are not altered in mutant mice. However, the IGF-I mRNA level is decreased in white adipose tissue (WAT) of PPAR +/- mice and is not changed by acute administration of rhGH, suggesting an altered GH action in the mutant animals. Importantly, expression of the gene encoding the suppressor of cytokine signaling-2 (SOCS-2), which is an essential negative regulator of GH signaling, is strongly increased in the WAT of PPAR +/- mice. While the relationship between the altered GH signaling in WAT and reduced body size remains unclear, our results suggest a novel role of PPAR in GH signaling, which might participate to the metabolic disorder affecting insulin signaling in PPAR mutant mice.
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GH •
IGF-I •
SOCS-2
NURSA Molecule Pages Link:
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