title: Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig-2/SREBP-2 pathway.
abstract: METHODS
  Individuals deficient in vitamin D are more likely to have higher circulating cholesterol levels and cardiovascular diseases. However, the underlying mechanisms are still unclear.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Songtao
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Song
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Liuyi
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lv
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Zongxiang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Huiru
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Rennan
authors.initials: R
authors.lastname: Feng
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Na
authors.affiliation: Institute for Nutrisciences and Health, National Research Council Canada, Charlottetown, PE, Canada.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.|Research Institute of Food, Nutrition and Health, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, China.|Research Institute of Food, Nutrition and Health, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, China.
authors.forename: Changhao
authors.initials: C
authors.lastname: Sun
mesh_terms: D000328:Adult; D000818:Animals; D044466:Asian People; D002681:China; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D003430:Cross-Sectional Studies; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*; D014807:Vitamin D / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000378:metabolism*
chemical_list: C467727:INSIG2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018167:Receptors, Calcitriol; C497390:SREBF2 protein, human; D051782:Sterol Regulatory Element Binding Protein 2; C579457:VDR protein, human; D014807:Vitamin D; D002784:Cholesterol
keywords: Cholesterol; Insig-2; Transcriptional activity; Vitamin D deficiency; Vitamin D receptor