Editors' ChoiceFetal Metabolic Programming

Dad’s Diet and Baby’s Metabolism

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Science Translational Medicine  12 Jan 2011:
Vol. 3, Issue 65, pp. 65ec4
DOI: 10.1126/scitranslmed.3002104

We’ve all heard the saying, “You are what you eat.” Well, maybe it would be more correct to say, “You are what your parents eat.” Diet and nutrition have long been known to influence epigenetically inherited traits, particularly the metabolic programming of the fetus. Yet, most research on the transgenerational effects of nutrition has focused on the maternal diet and the intrauterine environment. However, new results show that the paternal diet is also important.

In an elegant series of experiments in mice, Carone et al. showed that the offspring of males fed a low-protein diet had increased hepatic expression of many genes involved in cholesterol and lipid biosynthesis and decreased levels of cholesterol esters—which are associated with atherosclerosis—as compared with that of the offspring of males fed a control diet. A number of growth-associated microRNAs also had increased expression in the livers of offspring from fathers fed low-protein diets as compared with those of fathers fed control diets. Furthermore, epigenomic profiling of livers from offspring whose fathers were fed low-protein diets revealed numerous changes in cytosine methylation—a widespread DNA modification that is environmentally responsive and carries transgenerational heritable information—compared with that of livers from control offspring. In particular, a substantial (~30%) increase in methylation was found in a putative enhancer region of the key lipid regulator gene, Ppara, which was correlated with reduced expression of this gene.

In summary, Carone et al.’s findings demonstrate that paternal diet affects metabolic programming in the offspring and that epigenetic information that is responsive to environmental conditions is carried in sperm. Given recent epidemiological data showing that limited food intake in paternal grandfathers is associated with an increased risk of cardiometabolic disease in grandchildren, these results appear directly relevant to human disease and reinforce the importance of both maternal and paternal diet and environmental exposures on the offspring’s health.

B. R. Carone et al., Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143, 1084–1096 (2010). [Abstract]

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