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ludc web

Sara Larsson

Research engineer

ludc web

Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice.

Author

  • Celine Fernandez
  • Marie Lindholm
  • Morten Krogh
  • Stephanie Lucas
  • Sara Larsson
  • Peter Osmark
  • Karin Berger
  • Jan Boren
  • Barbara A Fielding
  • Keith N Frayn
  • Cecilia Holm

Summary, in English

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.

Department/s

  • Molecular Endocrinology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Computational Biology and Biological Physics
  • Insulin Signal Transduction

Publishing year

2008

Language

English

Pages

820-831

Publication/Series

American Journal of Physiology: Endocrinology and Metabolism

Volume

295

Issue

July 29

Document type

Journal article

Publisher

American Physiological Society

Topic

  • Physiology

Status

Published

Research group

  • Molecular Endocrinology
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Insulin Signal Transduction

ISBN/ISSN/Other

  • ISSN: 1522-1555