Absence of HDL cholesteryl ester uptake in mice via SR-BI impairs an adequate adrenal glucocorticoid-mediated stress response to fasting

Journal of Lipid Research

Theo J.C. Van Berkel¹  Mieke Koenders¹  Menno Hoekstra¹  Reeni B. Hildebrand¹  Illiana Meurs¹  Miranda Van Eck¹  Ruud Out¹  J. Kar Kruijt¹ 

[1] Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, 2300RA Leiden, The Netherlands;

关键词: scavenger receptor class B type I;    high density lipoprotein;    hormones;   

DOI  :  

来源: DOAJ

【 摘 要 】

Receptor-mediated cholesterol uptake has been suggested to play a role in maintaining the adrenal intracellular free cholesterol pool and the ability to produce hormones. Therefore, in the current study, we evaluated the importance of scavenger receptor class B type I (SR-BI)-mediated cholesteryl ester uptake from HDL for adrenal glucocorticoid hormone synthesis in vivo. No difference was observed in the plasma level of corticosterone between SR-BI-deficient and wild-type mice under ad libitum feeding conditions. Overnight fasting (∼16 h) stimulated the plasma level of corticosterone by 2-fold in wild-type mice. In contrast, no effect of fasting on plasma corticosterone levels was observed in SR-BI-deficient mice, leading to a 44% lower plasma corticosterone level compared with their wild-type littermate controls. In parallel, an almost complete depletion of lipid stores in the adrenal cortex of fasted SR-BI-deficient mice was observed. Plasma adrenocorticotropic hormone levels were increased by 5-fold in fasted SR-BI-deficient mice. SR-BI deficiency induced marked changes in the hepatic expression of the glucocorticoid-responsive genes cholesterol 7α-hydroxylase, HMG-CoA synthase, apolipoprotein A-IV, corticosteroid binding globulin, interleukin-6, and tumor necrosis factor-α, which coincided with a 42% decreased plasma glucose level under fasting conditions. In conclusion, we show that the absence of adrenal HDL cholesteryl ester uptake in SR-BI-deficient mice impairs the adrenal glucocorticoid-mediated stress response to fasting as a result of adrenal glucocorticoid insufficiency and attenuated liver glucocorticoid receptor signaling, leading to hypoglycemia under fasting conditions.

【 授权许可】

Unknown