Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue

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Samavat, J, Boachie, J, McTernan, PG ORCID: https://orcid.org/0000-0001-9023-0261, Christian, M ORCID: https://orcid.org/0000-0002-1616-4179, Saravanan, P and Adaikalakoteswari, A ORCID: https://orcid.org/0000-0003-2974-3388, 2025. Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue. BMC Medicine, 23 (1): 232. ISSN 1741-7015

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Official URL: https://doi.org/10.1186/s12916-025-04056-4

Abstract

Background: Adipose tissue (AT) responds to excess calorie intake; however, the deficit in micronutrients accompanied by the modern lifestyle is often overlooked. Micronutrient deficiency in pregnancy, particularly vitamin B12 (B12), is commonly associated with higher adiposity, dyslipidemia, and type 2 diabetes (T2D). Studies have demonstrated that dyslipidemia can trigger pro-inflammatory status. However, the release of the pro-inflammatory factors in a tissue-specific micronutrient deficient environment is unexplored. Therefore, we investigated the role of B12 deficiency on lipid metabolism and inflammatory mediators in both in vitro and ex vivo models including human pre-adipocytes, primary adipocytes, mature human white AT (WAT), and its association with metabolic risk.

Methods: Paired abdominal subcutaneous and omental WAT (ScWAT and OmWAT) were chosen based on serum B12 (< 150 pM) from 115 Caucasian pregnant women. Human primary Sc adipocytes from women with different BMI (lean, overweight, obese, morbidly obese) and pre-adipocyte cell line (Chub-S7) were differentiated in various concentrations of B12. Serum B12, folate, lipids, cytokines, biochemical parameters, gene expression, intracellular triglyceride (TG), and mitochondrial function were assessed.

Results: In pregnant women with low B12 levels, BMI and serum TG were significantly higher, and high-density lipoprotein (HDL) was lower (p < 0.05). B12 deficiency in both depots of AT correlated with higher expression of genes in fatty acid (FA) synthesis, elongation, desaturation, TG synthesis, and reduced fatty acid oxidation (FAO) (p < 0.05). In vitro adipocytes with low B12 demonstrated that TG synthesis utilizing radiolabeled FA was higher and mitochondrial function was impaired. We also found that the expression of pro-inflammatory cytokines in AT was increased, and circulatory cytokines inversely associated with serum B12 (p < 0.05).

Conclusions: Our novel data highlights that B12 deficiency dysregulates lipids and induces inflammation in AT and circulation, which could contribute to adipocyte dysfunction exacerbating cardiometabolic risk during pregnancy.

Item Type:	Journal article
Publication Title:	BMC Medicine
Creators:	Samavat, J., Boachie, J., McTernan, P.G., Christian, M., Saravanan, P. and Adaikalakoteswari, A.
Publisher:	Springer Science and Business Media LLC
Date:	2025
Volume:	23
Number:	1
ISSN:	1741-7015
Identifiers:	Number Type 10.1186/s12916-025-04056-4 DOI 2429671 Other
Rights:	© The Author(s) 2025. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
Divisions:	Schools > School of Science and Technology
Record created by:	Laura Borcherds
Date Added:	24 Apr 2025 08:45
Last Modified:	24 Apr 2025 08:45
URI:	https://irep.ntu.ac.uk/id/eprint/53442