Epigenetic Obesity In The Fruit FlyThursday, April 16, 2015
Regular readers are well aware of the considerable evidence now supporting the notion that inter-generational transmission of obesity risk through epigenetic modification may well be a key factor in the recent global rise in obesity rates (over the past 100 years or so).
Now a brief review article by Susan Ozanne from the University of Cambridge, UK, published in the New England Journal of Medicine, describes how researchers have now identified a clear and conserved epigenetic signature that is associated with obesity across species (from the fruit fly all the way to humans).
The article discusses how the transmission of susceptibility to obesity can occur as a consequence of “developmental programming,” whereby environmental factors (e.g. a high-fat diet) encountered at the point of conception and during fetal and neonatal life can permanently influences the structure, function, and metabolism of key organs in the offsprin, thus leading to an increased risk of diseases such as obesity later in life.
There is now evidence that such intergenerational transmission of disease can occur through environmental manipulation of both the maternal and paternal lines – thus, this is not something that is just a matter of maternal environment.
Thus, as Ozanne points out,
“Epigenetic mechanisms that influence gene expression have been proposed to mediate the effects of both maternal and paternal dietary manipulation on disease susceptibility in the offspring (these mechanisms include alterations in DNA methylation, histone modifications, and the expression of microRNAs).”
Work in the fruit fly has linked the effect of paternal sugar-feeding on the chromatin structure at a specific region of the X chromosome and transcriptome analysis of embryos generated from fathers fed a high-sugar diet, revealed dysregulation of transcripts encoding two proteins (one of them is called Su(var)) known to change chromatin structure and gene regulation.
Subsequent analyses of microarray data sets from humans and mice likewise revealed a depletion of the Su(var) proteins in three data sets from humans and in two data sets from mice.
“This finding is consistent with the possibility that the depletion of the Su(var) pathway may be brought about by an environmental insult to the genome that is associated with obesity.”
Not only do these studies provide important insights into just how generational transmission of obesity may work but it may also lead to the development of early tests to determine the susceptibility of individuals to the future development of conditions like obesity or diabetes based on epigenetic signatures.
All of this may be far more relevant for clinical practice than most readers may think – indeed, a focus on maternal (and now paternal?) health as a target to reduce the risk of childhood (and adult) obesity is already underway.
This issue will certainly be a “hot topic” at the Canadian Obesity Summit in Toronto later this month.