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

Olsson, B; Bohlooly-Y, M; Brusehed, O; Isaksson, OGP; Ahrén, Bo LU ; Olofsson, SO; Oscarsson, J and Tornell, J (2003) In American Journal of Physiology: Endocrinology and Metabolism 285(3). p.504-511
Abstract
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-alpha (PPARalpha) and genes involved in fatty acid activation, peroxisomal and mitochondrial beta-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... (More)
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-alpha (PPARalpha) and genes involved in fatty acid activation, peroxisomal and mitochondrial beta-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 PPARalpha and SREBP-1. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
fatty acids, DNA microarray, peroxisome, sterol regulatory, proliferator-activated receptor-alpha, transgenic mice, element-binding protein
in
American Journal of Physiology: Endocrinology and Metabolism
volume
285
issue
3
pages
504 - 511
publisher
American Physiological Society
external identifiers
  • pmid:12736163
  • wos:000184549400008
  • scopus:0041965899
ISSN
1522-1555
DOI
10.1152/ajpendo.00444.2002
language
English
LU publication?
yes
id
6c8139d2-25ef-4b1e-92ee-77cc199826f2 (old id 304747)
date added to LUP
2007-09-19 15:36:48
date last changed
2018-05-29 10:38:49
@article{6c8139d2-25ef-4b1e-92ee-77cc199826f2,
  abstract     = {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-alpha (PPARalpha) and genes involved in fatty acid activation, peroxisomal and mitochondrial beta-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 PPARalpha and SREBP-1.},
  author       = {Olsson, B and Bohlooly-Y, M and Brusehed, O and Isaksson, OGP and Ahrén, Bo and Olofsson, SO and Oscarsson, J and Tornell, J},
  issn         = {1522-1555},
  keyword      = {fatty acids,DNA microarray,peroxisome,sterol regulatory,proliferator-activated receptor-alpha,transgenic mice,element-binding protein},
  language     = {eng},
  number       = {3},
  pages        = {504--511},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Bovine growth hormone-transgenic mice have major alterations in hepatic expression of metabolic genes},
  url          = {http://dx.doi.org/10.1152/ajpendo.00444.2002},
  volume       = {285},
  year         = {2003},
}