Disturbed One-Carbon Metabolism Causing Adverse Reproductive Outcomes in Mice Is Associated with Altered Expression of Apolipoprotein AI and Inflammatory Mediators PPARa, Interferon-?, and Interleukin-10  

Oleh:

Mikael, Leonie G. ; Pancer, Jill ; Wu, Qing ; Rozen, Rima

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: JN: The Journal of Nutrition vol. 142 no. 03 (Mar. 2012), page 411-418.
Topik: BIOCHEMICAL; Molecular; Genetic Mechanisms

Ketersediaan

Perpustakaan FK Nomor Panggil: J42.K.2012.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

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 PPARa 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, PPARa, IFN?, 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 PPARa expression (mRNA and protein) was observed in ChDD-fed mice and was associated with increased methylation of a CpG dinucleotide in its promoter. Hepatic IFN? increased due to genotype, and placental IFN? 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 PPARa expression, possibly through promoter hypermethylation, and increase IFN? and decrease IL-10 levels. This disturbance of the T helper (Th1) (IFN?):Th2 (IL-10) ratio and the increase in inflammatory mediators may contribute to pregnancy complications.

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