Growth hormone is an important regulator of post-natal growth and metabolism. We have investigated the metabolic consequences of altered growth hormone signaling 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 STATS signaling respectively. These mutants result in altered liver metabolism, obesity and insulin resistance

A Bax

A Flores-Morales

A Palmer

Agnieszka M. Lichanska

AM Asatoor

AM Lichanska

B Olsson

B Richelsen

Cameron G. Anderson

CL Gavaghan

D Marion

D Voet

David J. Craik

DE Berryman

DH Lang

DP Simpson

E Holmes

E Park

EG Schuetz

F Franconi

G Dennis Jr

H Norrelund

H Satoh

Horst Joachim Schirra

HT Kiiveri

J Cavanagh

J Cheng

J Herrington

J Schleucher

JA Timbrell

JE Rowland

JK Nicholson

JR Baker

KH Clodfelter

KK Ho

L Braunschweiler

Linda Kerr

LM Raamsdonk

M Rance

M Rudling

MB Davidson

Michael J. Waters

N Moller

N Tsuboyama-Kasaoka

O Bouillanne

O Fiehn

P Parini

P Tollet-Egnell

PJ Kaisakia

R Pandey

RA Irizarry

S Bluher

S Harvey

S Mizushima

SB Heymsfield

SC Connor

SP Bessman

T Norwood

TA Clayton

TC Birdsall

V Sklenar

William J. Wilson

Y Zhou

Yihai Cao

PLoS ONE

English

PubMed

Crossref

Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study

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 changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age. CONCLUSIONS/SIGNIFICANCE: The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone receptor, and supports a potentially important role for taurine in enhancing beta-oxidation

Cameron G Anderson

William J Wilson

David J Craik

Michael J Waters

Agnieszka M Lichanska

Directory of Open Access Journals

Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study.

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.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 changes in expression of metabolic enzymes correlating with alterations in metabolite concentration both in urine and liver. Similarity of mutant 569 to the wild-type was seen in young mice, but the pattern of metabolites shifted to that of the 391 mutant as the 569 mice became obese after six months age.The metabonomic observations were consistent with the parallel analysis of gene expression and pathway mapping using microarray data, identifying metabolites and gene transcripts involved in hepatic metabolism, especially for taurine, choline and creatinine metabolism. The systems biology approach applied in this study provides a coherent picture of metabolic changes resulting from impaired STAT5 signalling by the growth hormone receptor, and supports a potentially important role for taurine in enhancing β-oxidation

Schirra Horst Joachim

Anderson Cameron G.

Wilson William J.

Kerr Linda

Craik David J.

Waters Michael J.

Lichanska Agnieszka M.

Public Library of Science (PLOS)

Schirra, Horst Joachim

Anderson, Cameron G.

Wilson, William J.

Kerr, Linda

Craik, David J.

Waters, Michael J.

Lichanska, Agnieszka M.

University of Queensland eSpace

Altered metabolism of growth hormone receptor mutant mice: a combined NMR metabonomics and microarray study

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Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study

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