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Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):e39-46. doi: 10.1161/ATVBAHA.112.300784. Epub 2012 Nov 29.

Adrenal-specific scavenger receptor BI deficiency induces glucocorticoid insufficiency and lowers plasma very-low-density and low-density lipoprotein levels in mice.

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1
Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300RA Leiden, The Netherlands. hoekstra@lacdr.leidenuniv.nl

Abstract

OBJECTIVE:

We determined the physiological consequences of adrenocortical-specific deletion of scavenger receptor BI (SR-BI) function in C57BL/6 wild-type mice.

METHODS AND RESULTS:

One adrenal from 10-day-old SR-BI knockout (KO) mice or wild-type controls was transplanted under the renal capsule of adrenalectomized C57BL/6 recipient mice. The fasting plasma corticosterone level increased over time in transplanted mice. Corticosterone values in SR-BI KO transplanted mice remained ≈50% lower (P<0.001) as compared with wild-type transplanted mice, which coincided with adrenocortical lipid depletion. A 6.5-fold higher (P<0.01) plasma adrenocorticotropic hormone level was present in SR-BI KO transplanted mice reminiscent of primary glucocorticoid insufficiency. On feeding with cholic acid-containing high cholesterol/high fat diet, SR-BI KO transplanted mice exhibited a 26% (P<0.05) reduction in their liver triglyceride level. Hepatic myosin regulatory light chain interacting protein/inducible degrader of the low-density lipoprotein receptor mRNA expression was 48% (P<0.01) decreased in adrenal-specific SR-BI KO mice, which was paralleled by a marked decrease (-46%; P<0.01) in proatherogenic very-low-density and low-density lipoprotein levels.

CONCLUSIONS:

Adrenal-specific disruption of SR-BI function induces glucocorticoid insufficiency and lowers plasma very-low-density and low-density lipoprotein levels in atherogenic diet-fed C57BL/6 mice. These findings further highlight the interaction between adrenal high-density lipoprotein-cholesterol uptake by SR-BI, adrenal steroidogenesis, and the regulation of hepatic lipid metabolism.

PMID:
23202366
DOI:
10.1161/ATVBAHA.112.300784
[Indexed for MEDLINE]
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