Vitamin B12 insufficiency induces cholesterol biosynthesis by limiting s-adenosylmethionine and modulating the methylation of SREBF1 and LDLR genes

Clinical Epigenetics
Antonysunil AdaikalakoteswariGyanendra Tripathi

Abstract

The dietary supply of methyl donors such as folate, vitamin B12, betaine, methionine, and choline is essential for normal growth, development, and physiological functions through the life course. Both human and animal studies have shown that vitamin B12 deficiency is associated with altered lipid profile and play an important role in the prediction of metabolic risk, however, as of yet, no direct mechanism has been investigated to confirm this. Three independent clinical studies of women (i) non-pregnant at child-bearing age, (ii) in early pregnancy, and (iii) at delivery showed that low vitamin B12 status was associated with higher total cholesterol, LDL cholesterol, and cholesterol-to-HDL ratio. These results guided the investigation into the cellular mechanisms of induced cholesterol biosynthesis due to vitamin B12 deficiency, using human adipocytes as a model system. Adipocytes cultured in low or no vitamin B12 conditions had increased cholesterol and homocysteine levels compared to control. The induction of cholesterol biosynthesis was associated with reduced s-adenosylmethionine (AdoMet)-to-s-adenosylhomocysteine (AdoHcy) ratio, also known as methylation potential (MP). We therefore studied whether reduced MP could lead t...Continue Reading

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Citations

Apr 7, 2016·Surgery for Obesity and Related Diseases : Official Journal of the American Society for Bariatric Surgery·Harold BaysCraig Primack
Feb 7, 2016·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Antonysunil AdaikalakoteswariPonnusamy Saravanan
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Methods Mentioned

BETA
ChIP-seq
lipidation
PCR
protein assay

Software Mentioned

R
SPSS Statistics
Bioconductor
Limma
Qiagen PyroMark

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