HDL is redundant for adrenal steroidogenesis in LDLR knockout mice with a human-like lipoprotein profile

The contribution of HDL to adrenal steroidogenesis appears to be different between mice and humans. In the current study, we tested the hypothesis that a difference in lipoprotein profile may be the underlying cause. Hereto, we determined the impact of HDL deficiency on the adrenal glucocorticoid ou...

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Bibliographic Details
Published in:Journal of lipid research 2016-04, Vol.57 (4), p.631-637
Main Authors: Hoekstra, Menno, Van Eck, Miranda
Format: Article
Language:English
Subjects:
Animals
cholesterol
Cholesterol, HDL - blood
corticosterone
Corticosterone - blood
gene expression
high density lipoprotein
Humans
low density lipoprotein
low density lipoprotein receptor
Male
Mice
Mice, Knockout
Receptors, LDL - deficiency
Receptors, LDL - genetics
steroid hormones
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Summary:The contribution of HDL to adrenal steroidogenesis appears to be different between mice and humans. In the current study, we tested the hypothesis that a difference in lipoprotein profile may be the underlying cause. Hereto, we determined the impact of HDL deficiency on the adrenal glucocorticoid output in genetically modified mice with a human-like lipoprotein profile. Genetic deletion of APOA1 in LDL receptor (LDLR) knockout mice was associated with HDL deficiency and a parallel increase in the level of cholesterol associated with nonHDL fractions. Despite a compensatory increase in the adrenal relative mRNA expression levels of the cholesterol synthesis gene, HMG-CoA reductase, adrenals from APOA1/LDLR double knockout mice were severely depleted of neutral lipids, as compared with those of control LDLR knockout mice. However, basal corticosterone levels and the adrenal glucocorticoid response to stress were not different between the two types of mice. In conclusion, we have shown that HDL is not critical for proper adrenal glucocorticoid function when mice are provided with a human-like lipoprotein profile. Our findings provide the first experimental evidence that APOB-containing lipoproteins may facilitate adrenal steroidogenesis, in an LDLR-independent manner, in vivo in mice.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M066019