The study, published the Proceedings of the National Academy of Sciences (PNAS), investigated how environmental pressures – in this case the mother’s diet while pregnant – can affect the expression of genes in their offspring.
The research found that when pregnant rats are fed a low-protein diet, their offspring are smaller, but have normal glucose metabolism until they are young adults, when they develop an age-related loss of glucose intolerance.
“Our findings reveal a novel mechanism by which maternal diet and aging interact through epigenetic processes to determine our risk of age-associated diseases,” said Dr Miguel Constancia, from the University of Cambridge, senior co-author of the paper.
“We show that the transcription factor Hnf4a, which has been implicated in the etiology of type 2 diabetes, is epigenetically regulated by maternal diet and aging,” explained the authors.
The researchers said it is well established that environmental factors interact with genes throughout life, affecting the expression of those genes and, consequently, tissue function and disease risk, and noted that previous studies have revealed that maternal diet can affect the physical health of the offspring.
Constancia and colleagues explained that prior research has shown that the gene hepatocyte nuclear factor 4-alpha (HNF 4-alpha) plays an important role both during development of the pancreas and later in the production of insulin, and suggested that diet during pregnancy may influence the expression of this gene later in life – thereby influencing the risk of diabetes.
Other research has linked HNF 4-alpha to a genetic region known as the P2 promoter.
The new study assessed whether maternal diet was linked to the functioning of HNF 4-alpha and the P2 promoter region in the pancreas.
The researchers collected pancreatic cells from rats aged three and 15 months, whose mother had been exposed to a normal or a low-protein diet during pregnancy. They then compared structure and function of parts of the DNA between the ‘normal’ and ‘low’ protein groups.
Constancia and his co-workers reported that the offspring of rats fed a normal diet had greater levels of HNF 4-alpha than those born to malnourished mothers. They said that the offspring of poorly fed mothers also showed evidence of malfunctions in particular parts of their DNA and this was slightly worse in older rats.
The authors concluded that their study had identified “a fundamental mechanism by which diet interacts with the genes during critical periods of development."
Adding that suboptimal nutrition during early life modifies interactions in HNF 4-alpha, which may lead to malfunctioning pancreatic cells and the subsequent development of type 2 diabetes.
Commenting on the research, the UK website NHS choices highlighted the fact that the research was conducted in rats, and therefore may not translate into humans.
“Animal research is important, but it is preliminary and the physiology of rats and humans differs. …While these researchers have established that the DNA region they were studying in rats was also present in human pancreatic cells, they have yet to prove that maternal diet has a similar effect on these regions in human offspring,” said NHS choices.
Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation, added that the new research was “no reason for expectant mothers to be unduly worried”, stressing that the findings do not change advice that pregnant women should try to eat a healthy, balanced diet.
Source: Proceedings of the National Academy of Sciences (PNAS)
Published online ahead of print, doi: 10.1073/pnas.1019007108
“Maternal diet and aging alter the epigenetic control of a promoter–enhancer interaction at the Hnf4a gene in rat pancreatic islets”
Authors: I, Sandovici, N.H. Smith, M.D. Nitert, M. Ackers-Johnson, et al