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Publication : Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.

First Author  Fernandez C Year  2008
Journal  Am J Physiol Endocrinol Metab Volume  295
Issue  4 Pages  E820-31
PubMed ID  18664600 Mgi Jnum  J:141973
Mgi Id  MGI:3820144 Doi  10.1152/ajpendo.90206.2008
Citation  Fernandez C, et al. (2008) Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice. Am J Physiol Endocrinol Metab 295(4):E820-31
abstractText  Transcriptomics analysis revealed that genes involved in hepatic de novo cholesterol synthesis were downregulated in fed HSL-null mice that had been on a high-fat diet (HFD) for 6 mo. 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 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, are the main mechanism underlying the imbalance in cholesterol metabolism in HSL-null mice.
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