Metabolic imprinting

Maternal overnutrition can have detrimental effects on the health of the offspring later in life. This area is less well studied and understood but some progress has been made in identifying specific genes that are affected.^[7] Studies have investigated hypermethylation of DNA and found it to be higher in obese mothers to those of a healthy BMI.^[11] More specific studies have investigated Leptin (LEP) as a possible gene which is altered via metabolic imprinting in response to overnutrition in utero, and found hypermethylation of LEP in the placenta of those born to overly nourished mothers.^[12] This hypermethylation has been found to cause changes in the levels of circulating Leptin, as well as to leptin sensitivity and the development of neural circuits involved in the control of homeostasis which causes the higher risk of metabolic disease.

Upon investigation it was found that a mother who was obese before conception was likely to have a higher level of placental LEP than the placenta of a mother of a healthy weight.^[12] One strategy for overcoming obesity is the use of gastric bypass and other such surgeries, while this does not entirely alleviate the risk of altered metabolic imprinting it has been found that siblings born post maternal surgery are less likely to have as high body fat percentages than over nutrition as siblings born before the surgery.^[13]

Paternal overnutrition can also have a detrimental effect and new-borns have shown changes in methylation of DNA generally, with substantial hypomethylation at the gene Insulin-like Growth factor 2 (IGF2). However, this topic is much less studied than maternal nutrition.^[13]

An increase in certain hormones such as oestrogen, progesterone, human placental lactogen, human placental growth hormone and cortisol during the second and third trimester of pregnancy cause an increase in insulin resistance. This increase in insulin resistance and following increase in insulin secretion ensures that the foetus develops a normal glucose tolerance.^[14] Gestational Diabetes Mellitus (GDM) arises when beta cells do not secrete enough insulin to adopt to the insulin resistance triggered by pregnancy, which leads to mild hyperglycaemia.^[15]

Although the mechanisms are still largely unknown, foetus exposure to GDM and maternal diabetes has been shown to lead to lifelong metabolic complications because of metabolic imprinting. The risk of Type II diabetes developing in offspring is significantly higher in offspring where the mother was diagnosed with Type II diabetes before pregnancy rather than after. In addition, the age at which offspring are diagnosed with Type 2 diabetes is significantly younger in offspring exposed to maternal diabetes/GDM than those who are not. It is suggested that this is a result of DNA methylation during foetal development.^[14]