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Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice.

Fernandez, Celine LU ; Lindholm, Marie LU ; Krogh, Morten LU ; Lucas, Stephanie LU ; Larsson, Sara LU ; Osmark, Peter LU ; Berger, Karin LU ; Boren, Jan; Fielding, Barbara A and Frayn, Keith N, et al. (2008) In American Journal of Physiology: Endocrinology and Metabolism 295(July 29). p.820-831
Abstract
Transcriptomics analysis revealed that genes involved in hepatic de novo cholesterol synthesis were down-regulated in fed HSL-null mice that had been on high-fat diet (HFD) for 6 months. This finding prompted a further analysis of cholesterol metabolism in HSL-null mice, which was performed in fed and 16-h fasted mice on a normal chow diet (ND) or a HFD regimen. Plasma cholesterol was elevated in HSL-null mice, in all tested conditions, as a result of cholesterol enrichment of HDL and VLDL. Hepatic esterified cholesterol content and ATP binding cassette transporter A1 (ABCA1) mRNA and protein levels were increased in HSL-null mice regardless of the dietary regimen. Unsaturated fatty acid composition of hepatic triglycerides was modified in... (More)
Transcriptomics analysis revealed that genes involved in hepatic de novo cholesterol synthesis were down-regulated in fed HSL-null mice that had been on high-fat diet (HFD) for 6 months. This finding prompted a further analysis of cholesterol metabolism in HSL-null mice, which was performed in fed and 16-h fasted mice on a normal chow diet (ND) or a HFD regimen. Plasma cholesterol was elevated in HSL-null mice, in all tested conditions, as a result of cholesterol enrichment of HDL and VLDL. Hepatic esterified cholesterol content and ATP binding cassette transporter A1 (ABCA1) mRNA and protein levels were increased in HSL-null mice regardless of the dietary regimen. Unsaturated fatty acid composition of hepatic triglycerides was modified in fasted HSL-null mice on ND and HFD. The increased ABCA1 expression had no major effect on cholesterol efflux from HSL-null mouse hepatocytes. Taken together, the results of this study suggest that HSL plays a critical role in the hydrolysis of cytosolic cholesteryl esters and that increased levels of hepatic cholesteryl esters, due to lack of action of HSL in the liver, is the main mechanism underlying the imbalance in cholesterol metabolism in HSL-null mice. Key words: lipoproteins, unsaturated fatty acids, high-fat diet, microarray. (Less)
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Contribution to journal
publication status
published
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in
American Journal of Physiology: Endocrinology and Metabolism
volume
295
issue
July 29
pages
820 - 831
publisher
American Physiological Society
external identifiers
  • PMID:18664600
  • Scopus:56049108571
ISSN
1522-1555
DOI
10.1152/ajpendo.90206.2008
language
English
LU publication?
yes
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5cf8018f-975b-4698-aa2c-d6fc033e9206 (old id 1223701)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18664600?dopt=Abstract
date added to LUP
2008-09-10 11:36:12
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2016-10-13 04:36:37
@misc{5cf8018f-975b-4698-aa2c-d6fc033e9206,
  abstract     = {Transcriptomics analysis revealed that genes involved in hepatic de novo cholesterol synthesis were down-regulated in fed HSL-null mice that had been on high-fat diet (HFD) for 6 months. This finding prompted a further analysis of cholesterol metabolism in HSL-null mice, which was performed in fed and 16-h fasted mice on a normal chow diet (ND) or a HFD regimen. Plasma cholesterol was elevated in HSL-null mice, in all tested conditions, as a result of cholesterol enrichment of HDL and VLDL. Hepatic esterified cholesterol content and ATP binding cassette transporter A1 (ABCA1) mRNA and protein levels were increased in HSL-null mice regardless of the dietary regimen. Unsaturated fatty acid composition of hepatic triglycerides was modified in fasted HSL-null mice on ND and HFD. The increased ABCA1 expression had no major effect on cholesterol efflux from HSL-null mouse hepatocytes. Taken together, the results of this study suggest that HSL plays a critical role in the hydrolysis of cytosolic cholesteryl esters and that increased levels of hepatic cholesteryl esters, due to lack of action of HSL in the liver, is the main mechanism underlying the imbalance in cholesterol metabolism in HSL-null mice. Key words: lipoproteins, unsaturated fatty acids, high-fat diet, microarray.},
  author       = {Fernandez, Celine and Lindholm, Marie and Krogh, Morten and Lucas, Stephanie and Larsson, Sara and Osmark, Peter and Berger, Karin and Boren, Jan and Fielding, Barbara A and Frayn, Keith N and Holm, Cecilia},
  issn         = {1522-1555},
  language     = {eng},
  number       = {July 29},
  pages        = {820--831},
  publisher    = {ARRAY(0x92e6d60)},
  series       = {American Journal of Physiology: Endocrinology and Metabolism},
  title        = {Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice.},
  url          = {http://dx.doi.org/10.1152/ajpendo.90206.2008},
  volume       = {295},
  year         = {2008},
}