title: Altered growth in male peroxisome proliferator-activated receptor gamma (PPARgamma) heterozygous mice: involvement of PPARgamma in a negative feedback regulation of growth hormone action.
abstract: The peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma allele has been mutated reveals that male PPARgamma heterozygous (PPARgamma +/-) 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 PPARgamma- specific antagonist. Monosodium glutamate treatment, which induces weight gain and alters body growth in wild-type mice, further aggravates the growth defect of PPARgamma +/- mice. The levels of circulating GH and that of its downstream effector, IGF-I, are not altered in mutant mice. However, the IGF-I mRNA level is decreased in white adipose tissue (WAT) of PPARgamma +/- mice and is not changed by acute administration of recombinant human GH, suggesting an altered GH action in the mutant animals. Importantly, expression of the gene encoding the suppressor of cytokine signaling-2, which is an essential negative regulator of GH signaling, is strongly increased in the WAT of PPARgamma +/- mice. Although the relationship between the altered GH signaling in WAT and reduced body size remains unclear, our results suggest a novel role of PPARgamma in GH signaling, which might contribute to the metabolic disorder affecting insulin signaling in PPARgamma mutant mice.
authors.affiliation: Center for Integrative Genomics, NCCR Frontiers in Genetics, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rieusset
authors.forename: Josiane
authors.initials: J
authors.lastname: Seydoux
authors.forename: Silvia I
authors.initials: SI
authors.lastname: Anghel
authors.forename: Pascal
authors.initials: P
authors.lastname: Escher
authors.forename: Liliane
authors.initials: L
authors.lastname: Michalik
authors.forename: Nguan
authors.initials: N
authors.lastname: Soon Tan
authors.forename: Daniel
authors.initials: D
authors.lastname: Metzger
authors.forename: Pierre
authors.initials: P
authors.lastname: Chambon
authors.forename: Walter
authors.initials: W
authors.lastname: Wahli
authors.forename: Béatrice
authors.initials: B
authors.lastname: Desvergne
mesh_terms: D000818:Animals; D001483:Base Sequence; D001823:Body Composition; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D017931:DNA Primers; D005246:Feedback; D006128:Growth / Q000235:genetics / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology*; D006579:Heterozygote; D007328:Insulin / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D047495:PPAR gamma / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping
chemical_list: D017931:DNA Primers; D007328:Insulin; D047495:PPAR gamma; D013006:Growth Hormone; D004247:DNA