Document Detail

LCAT deficiency in mice is associated with a diminished adrenal glucocorticoid function.
MedLine Citation:
PMID:  23178225     Owner:  NLM     Status:  MEDLINE    
In vitro studies have suggested that HDL and apoB-containing lipoproteins can provide cholesterol for synthesis of glucocorticoids. Here we assessed adrenal glucocorticoid function in LCAT knockout (KO) mice to determine the specific contribution of HDL-cholesteryl esters to adrenal glucocorticoid output in vivo. LCAT KO mice exhibit an 8-fold higher plasma free cholesterol-to-cholesteryl ester ratio (P < 0.001) and complete HDL-cholesteryl ester deficiency. ApoB-containing lipoprotein and associated triglyceride levels are increased in LCAT KO mice as compared with C57BL/6 control mice (44%; P < 0.05). Glucocorticoid-producing adrenocortical cells within the zona fasciculata in LCAT KO mice are devoid of neutral lipids. However, adrenal weights and basal corticosterone levels are not significantly changed in LCAT KO mice. In contrast, adrenals of LCAT KO mice show compensatory up-regulation of genes involved in cholesterol synthesis (HMG-CoA reductase; 516%; P < 0.001) and acquisition (LDL receptor; 385%; P < 0.001) and a marked 40-50% lower glucocorticoid response to adrenocorticotropic hormone exposure, endotoxemia, or fasting (P < 0.001 for all). In conclusion, our studies show that HDL-cholesteryl ester deficiency in LCAT KO mice is associated with a 40-50% lower adrenal glucocorticoid output. These findings further highlight the important novel role for HDL as cholesterol donor for the synthesis of glucocorticoids by the adrenals.
Menno Hoekstra; Suzanne J A Korporaal; Ronald J van der Sluis; Veronica Hirsch-Reinshagen; Andrea E Bochem; Cheryl L Wellington; Theo J C Van Berkel; Jan Albert Kuivenhoven; Miranda Van Eck
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-24
Journal Detail:
Title:  Journal of lipid research     Volume:  54     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-09     Completed Date:  2013-06-05     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  358-64     Citation Subset:  IM    
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MeSH Terms
Adrenal Glands / secretion*
Cholesterol Esters / metabolism
Corticosterone / secretion
Gene Knockout Techniques*
Glucocorticoids / secretion*
Hepatocytes / metabolism
Lipoproteins, HDL / metabolism
Phosphatidylcholine-Sterol O-Acyltransferase / genetics*,  metabolism*
Reg. No./Substance:
0/Cholesterol Esters; 0/Glucocorticoids; 0/HDL cholesteryl ester; 0/Lipoproteins, HDL; EC O-Acyltransferase; W980KJ009P/Corticosterone

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