Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice.

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Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice. / Fernandez, Celine; Lindholm, Marie; Krogh, Morten; Lucas, Stephanie; Larsson, Sara; Osmark, Peter; Berger, Karin; Boren, Jan; Fielding, Barbara A; Frayn, Keith N; Holm, Cecilia.

I: American Journal of Physiology: Endocrinology and Metabolism, Vol. 295, Nr. July 29, 2008, s. E820-E831.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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Fernandez, C, Lindholm, M, Krogh, M, Lucas, S, Larsson, S, Osmark, P, Berger, K, Boren, J, Fielding, BA, Frayn, KN & Holm, C 2008, 'Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice.', American Journal of Physiology: Endocrinology and Metabolism, vol. 295, nr. July 29, s. E820-E831. https://doi.org/10.1152/ajpendo.90206.2008

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Author

Fernandez, Celine ; Lindholm, Marie ; Krogh, Morten ; Lucas, Stephanie ; Larsson, Sara ; Osmark, Peter ; Berger, Karin ; Boren, Jan ; Fielding, Barbara A ; Frayn, Keith N ; Holm, Cecilia. / Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice. I: American Journal of Physiology: Endocrinology and Metabolism. 2008 ; Vol. 295, Nr. July 29. s. E820-E831.

RIS

TY - JOUR

T1 - Disturbed cholesterol homeostasis in hormone-sensitive lipase null mice.

AU - Fernandez, Celine

AU - Lindholm, Marie

AU - Krogh, Morten

AU - Lucas, Stephanie

AU - Larsson, Sara

AU - Osmark, Peter

AU - Berger, Karin

AU - Boren, Jan

AU - Fielding, Barbara A

AU - Frayn, Keith N

AU - Holm, Cecilia

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1152/ajpendo.90206.2008

DO - 10.1152/ajpendo.90206.2008

M3 - Article

C2 - 18664600

VL - 295

SP - E820-E831

JO - American Journal of Physiology - Endocrinology and Metabolism

JF - American Journal of Physiology - Endocrinology and Metabolism

SN - 1522-1555

IS - July 29

ER -