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

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...

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প্রধান লেখক: Fernandez, C, Lindholm, M, Krogh, M, Lucas, S, Larsson, S, Osmark, P, Berger, K, Borén, J, Fielding, B, Frayn, K, Holm, C
বিন্যাস: Journal article
ভাষা:English
প্রকাশিত: 2008
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author Fernandez, C
Lindholm, M
Krogh, M
Lucas, S
Larsson, S
Osmark, P
Berger, K
Borén, J
Fielding, B
Frayn, K
Holm, C
author_facet Fernandez, C
Lindholm, M
Krogh, M
Lucas, S
Larsson, S
Osmark, P
Berger, K
Borén, J
Fielding, B
Frayn, K
Holm, C
author_sort Fernandez, C
collection OXFORD
description 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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spelling oxford-uuid:888ac525-d219-478c-b5d0-eb665bff85092022-03-26T22:17:58ZDisturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:888ac525-d219-478c-b5d0-eb665bff8509EnglishSymplectic Elements at Oxford2008Fernandez, CLindholm, MKrogh, MLucas, SLarsson, SOsmark, PBerger, KBorén, JFielding, BFrayn, KHolm, CTranscriptomics 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.
spellingShingle Fernandez, C
Lindholm, M
Krogh, M
Lucas, S
Larsson, S
Osmark, P
Berger, K
Borén, J
Fielding, B
Frayn, K
Holm, C
Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.
title Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.
title_full Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.
title_fullStr Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.
title_full_unstemmed Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.
title_short Disturbed cholesterol homeostasis in hormone-sensitive lipase-null mice.
title_sort disturbed cholesterol homeostasis in hormone sensitive lipase null mice
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