Adrenal-Specific Scavenger Receptor BI Deficiency Induces Glucocorticoid Insufficiency and Lowers Plasma Very-Low-Density and Low-Density Lipoprotein Levels in Mice

作者：Hoekstra Menno^*; van der Sluis Ronald J; Van Eck Miranda; Van Berkel Theo J C

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2013, 33(2): E39-+.

DOI：10.1161/ATVBAHA.112.300784

• adrenal transplantation
• glucocorticoid
• liver
• scavenger receptor BI
• SR-BI knockout mice

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 approximate to 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.
Conclusion-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. (Arterioscler Thromb Vasc Biol. 2013;33:e39-46.)

• 出版日期2013-2