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1 Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
2 The Metabolism Unit, Center for Metabolism and Endocrinology, Department of Medicine, Karolinska Institutet, Huddinge, Sweden
3 Department of Mathematics, Uppsala University, Uppsala, Sweden
4 The Institute for Genomic Research, Rockville, MD, USA
* To whom correspondence should be addressed. E-mail: petra.tollet.egnell{at}cmm.ki.se.
Age-related changes in body composition and serum lipids resemble symptoms of adultonset growth hormone (GH) deficiency. GH treatment has been shown to normalize these changes in both GH deficient adult patients and elderly subjects. The aim of this study was to identify GH-responsive genes that might mediate positive effects of GH treatment on fuel metabolism and body composition. cDNA microarrays were used to analyze ageand GH-induced changes in gene expression patterns in male rats. Tissues analyzed were liver, adipose tissue and skeletal muscle from animals on or off GH treatment. A value of 1.5 was chosen to denote differences (increased or decreased expression) in the level of mRNA expression. In the liver, 7.3% of the expressed genes were affected by age and 6.5% by GH. Similar figures for the other tissues were 8.3% and 5.3% (fat), and 7.9% and 9.6% (muscle), respectively. Among the differentially expressed genes we identified several that encode proteins involved in fuel metabolism. Old rats were shown to have induced expression of genes involved in hepatic glucose oxidation and lipid synthesis, whereas these pathways were reduced in adipose tissue. GH treatment induced the expression of genes for lipid oxidation in liver and for glucose oxidation in skeletal muscle. In adipose tissue, GH reduced the expression of genes involved in lipogenesis even further. Changes in transcript levels were reflected in serum in terms of altered lipid profiles. Serum levels of triglycerides, HDL-cholesterol and total cholesterol were higher in the old animals than in the young and normalized by GH treatment.
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