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This Article Full Text Full Text (PDF) All Versions of this Article: 285/3/E504    most recent 00444.2002v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (31) Citing Articles via Google Scholar Google Scholar Articles by Olsson, B. Articles by Törnell, J. Search for Related Content PubMed PubMed Citation Articles by Olsson, B. Articles by Törnell, J.

Bovine growth hormone-transgenic mice have major alterations in hepatic expression of metabolic genes

Departments of ¹Physiology and ²Medical Biochemistry, Göteborg University, SE-405 30 Goteborg; ³Research Center for Endocrinology and Metabolism, Department of Internal Medicine and ⁴Wallenberg Laboratory for Cardiovascular Disease, Sahlgrenska University Hospital, SE-413 45 Goteborg; ⁵AstraZeneca Transgenics and Comparative Genomics Center, AstraZeneca Research and Development, SE-431 83 Molndal; and ⁶Department of Medicine, Lund University, SE-221 84 Lund, Sweden

Submitted 16 November 2002 ; accepted in final form 26 April 2003

Transgenic mice overexpressing growth hormone (GH) have been extensively used to study the chronic effects of elevated serum levels of GH. GH is known to have many acute effects in the liver, but little is known about the chronic effects of GH overexpression on hepatic gene expression. Therefore, we used DNA microarray to compare gene expression in livers from bovine GH (bGH)-transgenic mice and littermates. Hepatic expression of peroxisome proliferator-activated receptor- (PPAR) and genes involved in fatty acid activation, peroxisomal and mitochondrial -oxidation, and production of ketone bodies was decreased. In line with this expression profile, bGH-transgenic mice had a reduced ability to form ketone bodies in both the fed and fasted states. Although the bGH mice were hyperinsulinemic, the expression of sterol regulatory element-binding protein (SREBP)-1 and most lipogenic enzymes regulated by SREBP-1 was reduced, indicating that these mice are different from other insulin-resistant models with respect to expression of SREBP-1 and its downstream genes. This study also provides several candidate genes for the well-known association between elevated GH levels and cardiovascular disease, e.g., decreased expression of scavenger receptor class B type I, hepatic lipase, and serum paraoxonase and increased expression of serum amyloid A-3 protein. We conclude that bGH-transgenic mice display marked changes in hepatic genes coding for metabolic enzymes and suggest that GH directly or indirectly regulates many of these hepatic genes via decreased expression of PPAR and SREBP-1.

fatty acids; transgenic mice; DNA microarray; peroxisome proliferator-activated receptor-; sterol regulatory element-binding protein

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