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Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig‐2/SREBP‐2 pathway
Author(s) -
Li Songtao,
He Yujie,
Lin Song,
Hao Liuyi,
Ye Yaxin,
Lv Lin,
Sun Zongxiang,
Fan Huiru,
Shi Zhiping,
Li Jie,
Feng Rennan,
Na Lixin,
Wang Yanwen,
Li Ying,
Sun Changhao
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500425
Subject(s) - calcitriol receptor , medicine , endocrinology , cholesterol , vitamin d deficiency , vitamin d and neurology , vitamin , reductase , catabolism , ldl receptor , sterol , hmg coa reductase , biology , chemistry , metabolism , lipoprotein , biochemistry , enzyme
Scope 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 D 3 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.