Low vitamin B12 in pregnancy is associated with adipose derived circulating miRs targeting PPARγ and insulin resistance

Adaikalakoteswari, A ORCID: https://orcid.org/0000-0003-2974-3388, Vatish, M, Alam, MT, Ott, S, Kumar, S and Saravanan, P, 2017. Low vitamin B12 in pregnancy is associated with adipose derived circulating miRs targeting PPARγ and insulin resistance. The Journal of Clinical Endocrinology & Metabolism. ISSN 0021-972X

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Abstract

Context:
Low vitamin B12 (B12) during pregnancy is associated with higher maternal obesity, insulin resistance(IR) and gestational diabetes(GDM). B12 is a key co-factor in 1-carbon metabolism.
Objective:
We hypothesize that B12 plays a role in epigenetic regulation by altering circulating miRNAs(miRs) during adipocyte differentiation and results in an adverse metabolic phenotype.
Design, settings and main-outcome measure:
Human pre-adipocyte cell-line(Chub-S7) were differentiated in various B12 concentrations: Control(500nM), LowB12(0.15nM) and NoB12(0nM). Maternal blood samples(n=91) and subcutaneous adipose tissue (SAT)(n=42) were collected at delivery. Serum B12, folate, lipids, plasma 1-carbon metabolites, miR profiling, miR expression and gene expression were measured.
Results:
Our in vitro model demonstrated that adipocytes in B12 deficient conditions accumulated more lipids, had higher triglyceride levels and increased gene expression of adipogenesis and lipogenesis. MiR array screening revealed differential expression of 133miRs involving several metabolic pathways (adjusted p<0.05). Altered miR expression were observed in 12miRs related to adipocyte differentiation and function in adipocytes. Validation of this data in pregnant women with low B12, confirmed increased expression of adipo/lipogenic genes and altered miRs in SAT, and altered levels of 11 of the 12miRs in circulation. After adjusting for other possible confounders, multiple regression analysis revealed an independent association of B12 with BMI (β: -0.264; 95% CI: -0.469, -0.058; p=0.013) and was mediated by four circulating miRs targeting PPARγ and IR.
Conclusions:
Low B12 levels in pregnancy alters adipose derived circulating miRs, which may mediate an adipogenic and IR phenotype leading to obesity.

Item Type:	Journal article
Publication Title:	The Journal of Clinical Endocrinology & Metabolism
Creators:	Adaikalakoteswari, A., Vatish, M., Alam, M.T., Ott, S., Kumar, S. and Saravanan, P.
Publisher:	Oxford University Press
Date:	5 September 2017
ISSN:	0021-972X
Identifiers:	Number Type 10.1210/jc.2017-01155 DOI
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	30 Oct 2017 15:34
Last Modified:	05 Sep 2018 03:00
URI:	https://irep.ntu.ac.uk/id/eprint/31925

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