The contribution of individual lipoprotein species to the generation of the adrenal cholesterol pool used for the synthesis of anti-inflammatory glucocorticoid species remains unknown. Here we examined the impact of specific lowering of very low-density lipoprotein (VLDL) and low-density (LDL) levels on adrenal cholesterol and glucocorticoid homeostasis. Hereto, lethally-irradiated hypercholesterolemic apolipoprotein E (APOE) knockout mice received APOE-containing bone marrow from wild-type mice (n = 6) or APOE knockout control bone marrow (n = 10) and were subsequently fed a regular chow diet. Transplantation with wild-type bone marrow was associated with a 10-fold decrease in VLDL/LDL-cholesterol levels. No changes were observed in adrenal weights, adrenal cholesterol content, or basal plasma corticosterone levels. However, food deprivation-induced corticosterone secretion was 64% lower (P < 0.05) in wild-type bone marrow recipients as compared to APOE knockout bone marrow recipients, in the context of similar plasma adrenocorticotropic hormone (ACTH) levels. A parallel 19-29% decrease in adrenal relative mRNA expression levels of ACTH-responsive genes SR-BI (P < 0.01), STAR (P < 0.05), and CYP11A1 (P < 0.05) was detected. In support of relative glucocorticoid insufficiency, blood lymphocyte and eosinophil concentrations were respectively 2.4-fold (P < 0.01) and 8-fold (P < 0.001) higher in wild-type bone marrow recipients under food deprivation stress conditions. In conclusion, we have shown that a selective lowering of VLDL/LDL levels in APOE knockout mice through a transplantation with APOE-containing wild-type bone marrow is associated with a decreased maximal adrenal glucocorticoid output. Our studies provide experimental support for the hypothesis that, in vivo, VLDL/LDL serves as the primary source of cholesterol used for glucocorticoid synthesis during food deprivation stress.

中文翻译：

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VLDL / LDL是对食物缺乏的肾上腺糖皮质激素反应中胆固醇的主要来源。

单个脂蛋白种类对用于合成抗炎性糖皮质激素种类的肾上腺胆固醇库的产生的贡献仍然未知。在这里，我们检查了特异降低极低密度脂蛋白（VLDL）和低密度（LDL）水平对肾上腺胆固醇和糖皮质激素稳态的影响。迄今为止，接受致死性照射的高胆固醇血症性载脂蛋白E（APOE）剔除小鼠从野生型小鼠（n = 6）或APOE剔除对照骨髓（n = 10）接受了含APOE的骨髓，随后接受了常规食物。野生型骨髓移植与VLDL / LDL-胆固醇水平降低10倍有关。肾上腺重量，肾上腺胆固醇含量或基础血浆皮质酮水平未见变化。然而，在血浆血浆促肾上腺皮质激素（ACTH）水平相似的情况下，与APOE剔除骨髓接受者相比，野生型骨髓接受者食物剥夺引起的皮质酮分泌降低了64％（P <0.05）。检测到ACTH反应基因SR-BI（P <0.01），STAR（P <0.05）和CYP11A1（P <0.05）肾上腺相对mRNA表达水平平行下降19-29％。为了支持相对糖皮质激素不足，在食物缺乏应激条件下，野生型骨髓接受者的血淋巴细胞和嗜酸性粒细胞浓度分别高2.4倍（P <0.01）和8倍（P <0.001）。结论，我们已经表明，通过用含有APOE的野生型骨髓移植选择性降低APOE基因敲除小鼠的VLDL / LDL水平与最大肾上腺糖皮质激素输出降低有关。我们的研究为以下假设提供了实验依据：在体内，VLDL / LDL是食物缺乏压力期间用于糖皮质激素合成的胆固醇的主要来源。