Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig-2/SREBP-2 pathway.
Mol Nutr Food Res
; 60(4): 798-809, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26694996
ABSTRACT
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 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Deficiência de Vitamina D
/
Colesterol
/
Receptores de Calcitriol
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteína de Ligação a Elemento Regulador de Esterol 2
/
Proteínas de Membrana
Tipo de estudo:
Observational_studies
/
Prevalence_studies
/
Risk_factors_studies
Limite:
Adult
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Asia
Idioma:
En
Revista:
Mol Nutr Food Res
Assunto da revista:
CIENCIAS DA NUTRICAO
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
China