Altered Growth in Male Peroxisome Proliferator-Activated Receptor γ (PPARγ) Heterozygous Mice: Involvement of PPARγ in a Negative Feedback Regulation of Growth Hormone Action

The peroxisome proliferator-activated receptor γ (PPARγ) 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 PPARγ allele has been mutated reveals that male PPARγ heterozygous (PPARγ +/−) 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 PPARγ- specific antagonist. Monosodium glutamate treatment, which induces weight gain and alters body growth in wild-type mice, further aggravates the growth defect of PPARγ +/− 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 PPARγ +/− mice and is not changed by acute administration of recombinant human GH, suggesting an altered GH action in the mutant animals. Importantly...