Article ; Online: Maternal-Periconceptional Vitamin B12 Deficiency in Wistar Rats Leads to Sex-Specific Programming for Cardiometabolic Disease Risk in the Next Generation.
2023 Volume 153, Issue 12, Page(s) 3382–3396
Abstract: Background: Maternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts.: Objectives: This study assessed the effects of diet-induced maternal vitamin ... ...
| Abstract | Background: Maternal vitamin B12 deficiency plays a vital role in fetal programming, as corroborated by previous studies on murine models and longitudinal human cohorts. Objectives: This study assessed the effects of diet-induced maternal vitamin B12 deficiency on F1 offspring in terms of cardiometabolic health and normalization of these effects by maternal-periconceptional vitamin B12 supplementation. Methods: A diet-induced maternal vitamin B12 deficient Wistar rat model was generated in which female rats were either fed a control AIN-76A diet (with 0.01 g/kg vitamin B12) or the same diet with vitamin B12 removed. Females from the vitamin B12-deficient group were mated with males on the control diet. A subset of vitamin B12-deficient females was repleted with vitamin B12 on day 1 of conception. The offspring in the F1 generation were assessed for changes in body composition, plasma biochemistry, and molecular changes in the liver. A multiomics approach was used to obtain a mechanistic insight into the changes in the offspring liver. Results: We showed that a 36% reduction in plasma vitamin B12 levels during pregnancy in F0 females can lead to continued vitamin B12 deficiency (60%-70% compared with control) in the F1 offspring and program them for cardiometabolic adversities. These adversities, such as high triglycerides and low high-density lipoprotein cholesterol, were seen only among F1 males but not females. DNA methylome analysis of the liver of F1 3-mo-old offspring highlights sexual dimorphism in the alteration of methylation status of genes critical to signaling processes. Proteomics and targeted metabolomics analysis confirm that sex-specific alterations occur through modulations in PPAR signaling and steroid hormone biosynthesis pathway. Repletion of deficient mothers with vitamin B12 at conception normalizes most of the molecular and biochemical changes. Conclusions: Maternal vitamin B12 deficiency has a programming effect on the next generation and increases the risk for cardiometabolic syndrome in a sex-specific manner. Normalization of the molecular risk markers on vitamin B12 supplementation indicates a causal role. |
|---|---|
| MeSH term(s) | Pregnancy ; Male ; Humans ; Rats ; Animals ; Female ; Mice ; Rats, Wistar ; Vitamin B 12 Deficiency/metabolism ; Vitamin B 12 ; Reproduction ; Cardiovascular Diseases/etiology |
| Chemical Substances | Vitamin B 12 (P6YC3EG204) |
| Language | English |
| Publishing date | 2023-09-01 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 218373-0 |
| ISSN | 1541-6100 ; 0022-3166 |
| ISSN (online) | 1541-6100 |
| ISSN | 0022-3166 |
| DOI | 10.1016/j.tjnut.2023.08.032 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Uc I Zs.205: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.