Maternal folic acid supplementation in pregnant rats improves glucose tolerance in adult offspring — ASN Events

Maternal folic acid supplementation in pregnant rats improves glucose tolerance in adult offspring (#168)

Ezani Mohamed Jamil 1 , Patricia A Grant 1 , Simon Moretta 1 , Wee-Ching Kong 1 , Himawan Harryanto 1 , Kathryn L Gatford 1 , Julie A Owens 1
  1. Research Centre for Early Origins of Health and Disease, Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA, Australia

Background:  Folic acid supplementation (FAS) during pregnancy is recommended to prevent neural tube defects in offspring. Women can be exposed to up to 3 times the recommended dosage of folic acid however and that this may impact on other health outcomes in offspring, with maternal folate status linked to impaired insulin action and increased adiposity in children [1]. Maternal FAS (MFAS) in rats alters lipid metabolism in progeny [2], but outcomes for glucose control and insulin action are unknown.

Methods: Female Wistar rats were fed a control (C; 2 (n=22) or a FAS diet (FAS; 6 (n=23) from two weeks prior to mating until delivery. Glucose tolerance (intraperitoneal, IPGTT), insulin secretion (during IPGTT) and insulin tolerance (IPTT) were measured in offspring (males = 12; females =12 for each treatment group) at 3 and 6 months of age. Insulin action (disposition) was calculated as insulin secretion adjusted for sensitivity.

Results: MFAS altered glucose tolerance differently in males and females with age (TRT x SEX x AGE; p=0.02):  improving glucose tolerance in adult offspring (p= 0.036), the aged (p=0.035) and in young females (p=0.033), but increasing fasting plasma glucose in aged offspring (p=0.001). MFAS increased insulin sensitivity in aged adults only (p=0.032). MFAS reduced insulin secretion in adult offspring (p=0.004) and aged (p=0.04) and young adults (p= 0.019). MFAS reduced insulin disposition in adult offspring (p=0.042) and in young adults (p=0.047), particularly males (p= 0.01).

Conclusions: MFAS impairs fasting glycaemia, but improves glucose tolerance, in adult offspring, partly via increased insulin sensitivity and despite reduced insulin disposition or action, particularly in males. Therefore MFAS persistently modifies function of insulin sensitive tissues and the endocrine pancreas in offspring to affect their glucose control. Whether MFAS offspring exhibit further deterioration of fasting glycaemia with ageing and the mechanisms responsible, warrant investigation.

  1. Yajnik, C.S., et al., Vitamin B12 and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study . Diabetologia 2008. 51(1): p. 29-38.
  2. Chmurzynska, A., Fetal programming: link between early nutrition, DNA methylation, and complex diseases. Nutrition Reviews, 2010. 68(2): p. 87-98.