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altered metabolism of growth hormone receptor mutant mice a combined nmr metabonomics and microarray study改变代谢生长激素受体突变小鼠核磁共振代谢组学和微阵列研究相结合
Altered Metabolism of Growth Hormone Receptor
Mutant Mice: A Combined NMR Metabonomics and
Microarray Study
1 1 2 1 1
Horst Joachim Schirra *, Cameron G. Anderson , William J. Wilson , Linda Kerr , David J. Craik ,
Michael J. Waters1, Agnieszka M. Lichanska1¤
1 Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia, 2 CSIRO Mathematical and Information Sciences, Statistical
Bioinformatics - Health, New South Wales, Australia
Abstract
Background: Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the
metabolic consequences of altered growth hormone signalling in mutant mice that have truncations at position 569 and
391 of the intracellular domain of the growth hormone receptor, and thus exhibit either low (around 30% maximum) or no
growth hormone-dependent STAT5 signalling respectively. These mutations result in altered liver metabolism, obesity and
insulin resistance.
Methodology/Principal Findings: The analysis of metabolic changes was performed using microarray analysis of liver tissue
and NMR metabonomics of urine and liver tissue. Data were analyzed using multivariate statistics and Gene Ontology tools.
The metabolic profiles characteristic for each of the two mutant groups and wild-type mice were identified with NMR
metabonomics. We found decreased urinary levels of taurine, citrate and 2-oxoglutarate, and increased levels of
trimethylamine, creatine and creatinine when compared to wild-type mice. These results indicate significant changes in lipid
and choline metabolism, and were coupled with increased fat deposition, leading to obesity. The microarray analysis
identified
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