Abstract

In principle, organisms benefit by informing their immediate offspring of their prior environmental experiences so that the offspring can respond with changes in phenotype appropriate for the predicted future environment. Epigenetic information can be inherited through the mammalian germline, and, unlike DNA, represents a plausible transgenerational carrier of such environmental information. To test whether such transgenerational inheritance occurs in mammals, we carried out an expression profiling screen for genes in mice that responded to paternal diet. Offspring of males fed a low-protein diet increased the expression of many genes involved in lipid and cholesterol biosynthesis, relative to the offspring of males fed a control diet. The progeny of low protein diet fathers had dramatically decreased levels of cholesterol esters, a key factor in cardiovascular disease in humans. These results, in conjunction with recent human epidemiological data, suggest that one risk factor for obesity and cardiovascular disease is parental diet, and define a model system to study environmental reprogramming of the heritable epigenome.