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Mol Nutr Food Res. 2016 Apr;60(4):798-809. doi: 10.1002/mnfr.201500425. Epub 2016 Feb 2.

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

Li S1, He Y1, Lin S1, Hao L1, Ye Y1, Lv L1, Sun Z1, Fan H1, Shi Z1, Li J1, Feng R1, Na L1, Wang Y2, Li Y1,3, Sun C1,3.

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Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
Institute for Nutrisciences and Health, National Research Council Canada, Charlottetown, PE, Canada.
Research Institute of Food, Nutrition and Health, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China.



Individuals deficient in vitamin D are more likely to have higher circulating cholesterol levels and cardiovascular diseases. However, the underlying mechanisms are still unclear.


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.


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.


Cholesterol; Insig-2; Transcriptional activity; Vitamin D deficiency; Vitamin D receptor

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