Gestational Pre-Diabetes Modifies Leptin Gene in UteroThursday, August 26, 2010
One of the most exciting and biologically highly plausible reasons for the childhood obesity epidemic may well be that current generations are far more susceptible to obesity because of “epigenetic programming”.
Simply put, the notion is that exposure to an adverse fetal environment, as in the case of maternal obesity, diabetes or hypertension during pregnancy, can lead to a lifelong change in the genetic program of the offspring, making them genetically more prone to obesity.
Thus, although the children are born with the same genetic code as their parents, whether or not certain genes are “more” or “less” active, is determined by the fetal (and possibly early post-natal) environment.
While these “epigenetic” changes are well documented in animal studies, exactly which genes are affected in the context of intergenerational transmission of obesity is not clear.
A study by Luigi Bouchard and colleagues from Universit├® de Montr├®al, Canada, just published online in Diabetes Care, suggests that one of the modified genes may well be leptin, a key regulator of energy balance.
The researchers examined placental tissues as well as maternal and cord blood samples from 48 women, 23 of who had gestational impaired glucose tolerance (= gestational pre-diabetes).
Not only was there a positive association between the DNA methylation levels of the offspring’s leptin gene (measured in the placenta) and the glucose response to an oral glucose test, but there was also a negative relationship to placental leptin gene expression.
DNA methylation is a form of “epigenetic” modification that determines the extent to which a given gene is expressed┬áin vivo. Thus although the genetic code or DNA sequence for that gene may be identical between two individuals, variations in DNA methylation will determine how “active” this gene is in a given individual.
The authors conclude that impaired glucose tolerance during pregnancy is associated with epigentic modification of the leptin gene with potential functional impacts that could in part account for the detrimental health effects associated with fetal programming such as long-term increased risk of developing obesity and type 2 diabetes.
As I have noted before, obesity may well start in the womb, which is why recent recommendations have focussed on improving maternal health, including the prevention of excess weight gain during pregnancy, as a key strategy to reduce childhood obesity.
Bouchard L, Thibault S, Guay SP, Santure M, Monpetit A, St-Pierre J, Perron P, & Brisson D (2010). Leptin Gene Epigenetic Adaptation to Impaired Glucose Metabolism during Pregnancy. Diabetes care PMID: 20724651