The Role of Insulin‐Like Growth Factor‐1 in Programming of Offspring Adiposity by Maternal Folate/ Vitamin B12 Imbalance
Bibliographic record
Abstract
Introduction Developmental programming suggest that prenatal and early postnatal environment, such as maternal nutrition, can impact risk for chronic disease later in life. Recent population studies have reported greater insulin resistance and adiposity in children from mothers with adequate folate but low vitamin B12 (B12) status during pregnancy. Grain products in North America are fortified with folic acid to reduce the incidence of neural tube defects. Folate is required for methyl metabolism and is metabolically linked to vitamin B12. Low B12 status, even when folate is adequate, can trap folate in a metabolically inactive form. Folate deficiency is rare in Canada, yet approximately 1 in 20 Canadians are deficient in B12. The mechanisms underlying the relationship between maternal imbalance of folate/ B12 status and offspring adiposity and insulin resistance is not understood. A study recently reported that maternal B12 deficiency during pregnancy disrupts growth hormone (GH)/insulin‐like growth factor‐1 (IGF‐1) axis, resulting in growth retardation and bone malformation in the offspring. The objective of this study is to determine if programming of offspring adiposity by maternal folate/ B12 imbalance involves disturbances in the GH/IGF‐1 axis. Methods Female mice (C57BL/6J) were fed one of 3 diets: control (2mg folic acid/kg diet, M‐CON), supplemental FA (10mg/kg diet) with adequate B12 (SFA+B12), or supplemental FA without B12 (SFA‐B12). Dams were fed the diets 6 weeks prior to conception, through breeding, pregnancy, and lactation. One male and one female pup from each dam were weaned onto a control diet or a high‐fat (45% energy) diet. Tissue was harvested from offspring mice at 20 weeks post‐weaning. Serum IGF‐1 concentrations were quantified by ELISA. Hepatic Igf1 mRNA and Igfbp2 mRNA expression was quantified by Real‐Time PCR using the ΔΔ Ct method of relative quantification. The effect of maternal diet was determined by 1‐way ANOVA, separately in offspring fed the post weaning control diet and western diet. Results Female SFA‐B12 offspring fed the post weaning control diet had lower (p<0.05) serum IGF‐1 concentrations than M‐CON offspring and SFA+B12 offspring. Female SFA‐B12 offspring fed the post weaning western diet had lower (p=0.08) serum IGF‐1 concentrations than SFA+B12 offspring. No effect of maternal diet on serum IGF‐1 concentrations was observed in male offspring. Female SFA+B12 offspring fed the post weaning western diet had higher (p=0.008) hepatic Igf1 mRNA than M‐CON offspring. No effect of maternal diet on hepatic Igf1 mRNA was observed in male offspring. Male SFA‐B12 offspring fed the post weaning control diet had higher (p=0.028) hepatic Igfbp2 mRNA than M‐CON offspring. No effect of maternal diet on hepatic Igfbp2 mRNA was observed in female offspring. Conclusion These findings suggest a role for IGF‐1 in programming of offspring adiposity by maternal folate/ B12 imbalance. It is vital to understand the implications of folate/B12 imbalances, particularly during pregnancy. Support or Funding Information This work was supported by the NSERC Team Discovery Grant. Amanda M. Henderson is supported by the NSERC Canada Graduate Scholarships‐ Master's Program.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".