| First Author | Mikael LG | Year | 2012 |
| Journal | J Nutr | Volume | 142 |
| Issue | 3 | Pages | 411-8 |
| PubMed ID | 22259189 | Mgi Jnum | J:181924 |
| Mgi Id | MGI:5314439 | Doi | 10.3945/jn.111.151753 |
| Citation | Mikael LG, et al. (2012) Disturbed one-carbon metabolism causing adverse reproductive outcomes in mice is associated with altered expression of apolipoprotein AI and inflammatory mediators PPARalpha, interferon-gamma, and interleukin-10. J Nutr 142(3):411-8 |
| abstractText | Low dietary choline or deficiency of methylenetetrahydrofolate reductase (Mthfr) leads to hyperhomocysteinemia (Hhcy) and adverse reproductive outcomes. Homocysteine reduces synthesis of ApoAI, the major lipoprotein in HDL-cholesterol; ApoAI is regulated by PPARalpha and has antiinflammatory properties. Our aim was to determine whether pregnancy complications due to genetic or nutritional deficiencies in 1-carbon metabolism could relate to dysregulation of ApoAI and inflammatory mediators. We fed pregnant mice, with or without a deficiency of Mthfr, control or choline-deficient (ChDD) diets for 10-12 wk and examined levels of ApoAI, PPARalpha, IFNgamma, and IL-10. ApoAI mRNA was reduced in livers of Mthfr(+/-) mice and ApoAI protein was reduced due to Mthfr deficiency or choline deficiency in liver and plasma. Placental ApoAI protein was also reduced due to Mthfr genotype or choline-deficient diet and in developmentally delayed embryos. Reduced liver PPARalpha expression (mRNA and protein) was observed in ChDD-fed mice and was associated with increased methylation of a CpG dinucleotide in its promoter. Hepatic IFNgamma increased due to genotype, and placental IFNgamma was higher in Mthfr(+/-) ChDD-fed dams compared to Mthfr(+/+) mice fed ChDD or Mthfr(+/-) mice fed CD. IL-10 was reduced in livers of ChDD-fed mice. We propose that a deficiency of dietary choline or Mthfr leads to Hhcy and reduced expression of maternal ApoAI, with reduced ApoAI transfer to embryo. Disturbances in 1-carbon metabolism also reduce maternal PPARalpha expression, possibly through promoter hypermethylation, and increase IFNgamma and decrease IL-10 levels. This disturbance of the T helper (Th1) (IFNgamma):Th2 (IL-10) ratio and the increase in inflammatory mediators may contribute to pregnancy complications. |
