title: Total parenteral nutrition induces sustained hypomethylation of DNA in newborn guinea pigs.
abstract: BACKGROUND
  Neonatal total parenteral nutrition (TPN) is associated with animals with low glucose tolerance, body weight, and physical activity at adulthood. The early life origin of adult metabolic perturbations suggests a reprogramming of metabolism following epigenetic modifications induced by a change in the pattern of DNA expression. We hypothesized that peroxides contaminating TPN inhibit the activity of DNA methyltransferase (DNMT), leading to a modified DNA methylation state.
  
  
  METHODS
  Three groups of 3-d-old guinea pigs with catheters in their jugular veins were compared: (i) control: enterally fed with regular chow; (ii) TPN: fed exclusively with TPN (dextrose, amino acids, lipids, multivitamins, contaminated with 350 ± 29 μmol/l peroxides); (iii) H2O2: control + 350 μmol/l H2O2 intravenously. After 4 d, infusions were stopped and animals enterally fed. Half the animals were killed immediately after treatments and half were killed 8 wk later (n = 4-6 per group) for hepatic determination of DNMT activities and of 5'-methyl-2'-deoxycytidine (5MedCyd) levels, a marker of DNA methylation.
  
  
  RESULTS
  At 1 wk, DNMT and 5MedCyd were lower in the TPN and H2O2 groups as compared with controls. At 9 wk, DNMT remained lower in the TPN group, whereas 5MedCyd was lower in the TPN and H2O2 groups.
  
  
  CONCLUSIONS
  Administration of TPN or H2O2 early in life in guinea pigs induces a sustained hypomethylation of DNA following inhibition of DNMT activity.
authors: Department of Nutrition, University of Montréal, Montréal, Quebec, Canada.
authors: Sabrina
authors: S
authors: Yara
authors: Emile
authors: E
authors: Levy
authors: Wesam
authors: W
authors: Elremaly
authors: Thérèse
authors: T
authors: Rouleau
authors: Jean-Claude
authors: JC
authors: Lavoie
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019175:DNA Methylation; D006168:Guinea Pigs; D010289:Parenteral Nutrition, Total