The Role of Insulin‐Like Growth Factor‐1 in Programming of Offspring Adiposity by Maternal Folate/ Vitamin B12 Imbalance
Authors: Henderson Amanda M. , Aleliunas Rika E. , Tai Daven C. , Chem Nolan G. J. , Green Tim J. , Devlin Angela M. 
Published: November 2023

IntroductionDevelopmental 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.MethodsFemale 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 ΔΔCt 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.ResultsFemale 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.ConclusionThese 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 InformationThis work was supported by the NSERC Team Discovery Grant. Amanda M. Henderson is supported by the NSERC Canada Graduate Scholarships‐ Master's Program.