RNA-mediated paternal heredity of diet induced type II diabetes and obesity.

Epidemiological surveys first indicated that obesity and type II diabetes generated by lipid rich diets may be efficiently inherited, both paternally and maternally. This apparent exception to the fundamental law of non heritability of acquired characters was more recently documented in laboratory organisms but the transgenerational signal remained a matter of speculation. Here we show that experimental transfer to healthy one-cell embryos of testis RNA prepared from males raised on high-fat-diet (HFD) results in the development of obesity and diabetes in the adult. Body weight, fasting glucose levels, response to insulin, glucose tolerance, RNA levels of leptin and stearoyl-CoA desaturase were all affected in mice born after RNA microinjection to the same extent as in the progenitors and in their sexual offspring. Surprisingly, neither microarray hybridization nor deep sequencing of the inducer and control RNAs showed a differential expression of known regulators of adipogenesis, but only modest variations in a series of transcripts. Transgenerational maintenance appears as one instance of the RNA-mediated heredity of epigenetic traits previously demonstrated in experimental systems ranging from the worm to the mouse. The relationship between lipid-rich diet and changes in testicular RNAs on one side and the nature of the mark imprinted on the one-cell embryo by RNA transfer and responsible for pathological developments at later stages are questions of interest for future studies.