A father's diet before conception influences the likelihood of their child developing metabolic diseases, including diabetes, due to changes in sperm RNA.
Using data from over 3000 families and a mouse model, researchers at Helmholtz Munich, Germany, and the German Centre for Diabetes Research have demonstrated that the diet of a father before conception can impact on children's weight and risk of metabolic disease. This research, published in Nature, showed that diet can affect fragments of RNA carried by the sperm into the egg, changing the activity of metabolic genes.
'Our study shows that sperm exposed to a high-fat diet in the mouse epididymis led to offspring with an increased tendency to metabolic diseases,' said study leader Dr Raffaele Teperino, head of the environmental epigenetic research group at Helmholtz Munich.
Using data from the LIFE child cohort, the researchers identified a link between increased paternal body weight and the likelihood of a child having a metabolic disorder. This link was independent of the mother's weight. To test this directly, the researchers fed mice a high-fat diet for two weeks, then monitored their sperm and the metabolism of their offspring. Offspring of mice fed the high-fat diet had an increased incidence of glucose intolerance compared to mice fed a normal diet.
To investigate the mechanism, they studied differences in the mitochondria. The mitochondria are generally considered the powerhouse of the cell, providing energy, and therefore playing an important role in metabolism. Mitochondrial DNA produces proteins via an intermediate RNA. While mitochondrial DNA is only inherited from the mother, this research has identified small RNA molecules in mouse sperm which can affect the expression of mitochondrial genes involved in metabolism through epigenetic effects. The number of these RNA molecules was increased in a proportion of the mice fed the high fat diet.
'Our hypothesis that acquired phenotypes over the course of life, such as diabetes and obesity, are transmitted via epigenetic mechanisms across generations, is reinforced by this study. This occurs not only through the maternal line but, as our research results indicate, also through the paternal line'.
Key to the findings is that the changes are reversible. Mice that were fed a high-fat diet and then returned to a normal diet did not have offspring with an increased incidence of glucose intolerance,' explained co-author Professor Martin Hrabě de Angelis, research director at Helmholtz Munich. 'The reversibility provides opportunity for developing preventative health measures for potential fathers. However, first a better understanding of how RNA transferred in the sperm affects gene expression is required.'
'Our results suggest that preventive health care for men wishing to become fathers should receive more attention and that programs should be developed for this purpose, especially with regard to diet,' said Dr Teperino. 'This can reduce the risk of diseases like obesity and diabetes in children.'
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