Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals

Cell. 2010 Dec 23;143(7):1084-96. doi: 10.1016/j.cell.2010.12.008.


Epigenetic information can be inherited through the mammalian germline and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information 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 exhibited elevated hepatic expression of many genes involved in lipid and cholesterol biosynthesis and decreased levels of cholesterol esters, relative to the offspring of males fed a control diet. Epigenomic profiling of offspring livers revealed numerous modest (∼20%) changes in cytosine methylation depending on paternal diet, including reproducible changes in methylation over a likely enhancer for the key lipid regulator Ppara. These results, in conjunction with recent human epidemiological data, indicate that parental diet can affect cholesterol and lipid metabolism in offspring and define a model system to study environmental reprogramming of the heritable epigenome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biosynthetic Pathways
  • Cholesterol / biosynthesis
  • Cytosine / metabolism
  • DNA Methylation*
  • Diet, Protein-Restricted*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Genomic Imprinting*
  • Humans
  • Lipid Metabolism*
  • Liver / metabolism
  • Male
  • Mice


  • Cytosine
  • Cholesterol

Associated data

  • GEO/GSE25899