title: Maternal nutrition induces pervasive gene expression changes but no detectable DNA methylation differences in the liver of adult offspring.
abstract: OBJECTIVE
  Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we characterize the phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic changes induced by maternal diet in adult offspring.
  
  
  METHODS
  We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart. We then measured DNA methylation patterns in liver at selected loci and throughout the genome.
  
  
  RESULTS
  Maternal diet had a significant effect on the body weight of the offspring when they were fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. We did not detect any effect of the maternal diet on DNA methylation in the liver.
  
  
  CONCLUSIONS
  Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver.
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Cannon
authors.affiliation: Department of Genetics, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: David A
authors.initials: DA
authors.lastname: Buchner
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: James
authors.initials: J
authors.lastname: Hester
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Hadley
authors.initials: H
authors.lastname: Miller
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: Ephraim
authors.initials: E
authors.lastname: Sehayek
authors.affiliation: Department of Genetics, Case Western Reserve University, Cleveland, Ohio, United States of America; Pacific Northwest Research Institute, Seattle, Washington, United States of America.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Nadeau
authors.affiliation: Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Serre
mesh_terms: D000818:Animals; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D006128:Growth; D008099:Liver / Q000378:metabolism*; D008297:Male; D018811:Maternal Exposure; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL