Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue
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...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s12916-025-04056-4 |
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| author | Jinous Samavat Joseph Boachie Philip G. McTernan Mark Christian Ponnusamy Saravanan Antonysunil Adaikalakoteswari |
| author_facet | Jinous Samavat Joseph Boachie Philip G. McTernan Mark Christian Ponnusamy Saravanan Antonysunil Adaikalakoteswari |
| author_sort | Jinous Samavat |
| collection | DOAJ |
| description | 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. Graphical Abstract |
| format | Article |
| id | doaj-art-c8a7b7973c534b6aa88a64b5d316f935 |
| institution | OA Journals |
| issn | 1741-7015 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
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| series | BMC Medicine |
| spelling | doaj-art-c8a7b7973c534b6aa88a64b5d316f9352025-08-20T02:20:05ZengBMCBMC Medicine1741-70152025-04-0123111410.1186/s12916-025-04056-4Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissueJinous Samavat0Joseph Boachie1Philip G. McTernan2Mark Christian3Ponnusamy Saravanan4Antonysunil Adaikalakoteswari5Division of Health Sciences, Warwick Medical School, University of WarwickDivision of Health Sciences, Warwick Medical School, University of WarwickDepartment of Biosciences, School of Science and Technology, Nottingham Trent UniversityDivision of Health Sciences, Warwick Medical School, University of WarwickDivision of Health Sciences, Warwick Medical School, University of WarwickDivision of Health Sciences, Warwick Medical School, University of WarwickAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s12916-025-04056-4Vitamin B12Adipose tissueLow-grade inflammationLipid metabolismObesityPregnancy |
| spellingShingle | Jinous Samavat Joseph Boachie Philip G. McTernan Mark Christian Ponnusamy Saravanan Antonysunil Adaikalakoteswari Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue BMC Medicine Vitamin B12 Adipose tissue Low-grade inflammation Lipid metabolism Obesity Pregnancy |
| title | Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue |
| title_full | Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue |
| title_fullStr | Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue |
| title_full_unstemmed | Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue |
| title_short | Maternal B12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue |
| title_sort | maternal b12 deficiency during pregnancy dysregulates fatty acid metabolism and induces inflammation in human adipose tissue |
| topic | Vitamin B12 Adipose tissue Low-grade inflammation Lipid metabolism Obesity Pregnancy |
| url | https://doi.org/10.1186/s12916-025-04056-4 |
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