Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig-2/SREBP-2 pathway

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  1. Get@NRC: Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig-2/SREBP-2 pathway (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1002/mnfr.201500425
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TypeArticle
Journal titleMolecular Nutrition and Food Research
ISSN1613-4125
AbstractScope: Individuals deficient in vitamin D are more likely to have higher circulating cholesterol levels and cardiovascular diseases. However, the underlying mechanisms are still unclear. Methods and results: A cross-sectional survey, animal study, and in vitro experiments were conducted to investigate the effect and mechanisms of vitamin D deficiency on endogenous cholesterol metabolism. We demonstrated that vitamin D deficiency was positively associated with an increase of total serum cholesterol and low-density lipoprotein cholesterol levels in northern Chinese individuals. The vitamin D deficiency-induced increase of cholesterol concentration was mainly due to enhanced cholesterol biosynthesis rather than reduced catabolism. Under vitamin D deficiency, the transcriptional activity of vitamin D receptor (VDR) was decreased, leading to the downregulation of insulin-induced gene-2 (Insig-2) expression and thus its inhibitory role on sterol regulatory element-binding protein 2 activation; 3-hydroxy-3-methylglutaryl-coenzyme A reductase expression was accordingly increased. Vitamin D3 was protective against vitamin D deficiency-induced cholesterol increase by maintaining the transcriptional activity of VDR and Insig-2 expression. Conclusion: Vitamin D deficiency is associated with the increase of circulating cholesterol in the people of northern China by enhancing hepatic cholesterol biosynthesis, which was linked to the reduction of transcriptional activity of VDR.
Publication date
PublisherWiley
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); Aquatic and Crop Resource Development
Peer reviewedYes
NPARC number21277500
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Record identifierd9f18a14-b19a-4c80-b6d7-ab140d465283
Record created2016-03-09
Record modified2016-05-09
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