Disruption of lipid metabolism in the liver of the pregnant rat fed folate-deficient and methyl donor-deficient diets

Christopher John McNeil, Susan Hay, Garry Jonathan Rucklidge, Martin David Reid, Gary James Duncan, Christopher A. Maloney, William Rees

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (-F) or in three key methyl donors, folic acid, choline and methionine (-FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism. energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both -F and -FLMLC diets. The mRNA for PPAR alpha. and PPAR gamma and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the -FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the -F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the -FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.

Original languageEnglish
Pages (from-to)262-271
Number of pages10
JournalBritish Journal of Nutrition
Volume99
Issue number2
DOIs
Publication statusPublished - Feb 2008

Keywords

  • methionine
  • choline
  • folic acid
  • endoplasmic reticulum
  • phosphatidylethanolamine-N-methyltransferase
  • oxidative stress
  • fatty liver
  • membrane
  • disease
  • mice
  • localization
  • lipoproteins
  • vitamin-B-12
  • cholesterol

Cite this

Disruption of lipid metabolism in the liver of the pregnant rat fed folate-deficient and methyl donor-deficient diets. / McNeil, Christopher John; Hay, Susan; Rucklidge, Garry Jonathan; Reid, Martin David; Duncan, Gary James; Maloney, Christopher A.; Rees, William.

In: British Journal of Nutrition, Vol. 99, No. 2, 02.2008, p. 262-271.

Research output: Contribution to journalArticle

McNeil, Christopher John ; Hay, Susan ; Rucklidge, Garry Jonathan ; Reid, Martin David ; Duncan, Gary James ; Maloney, Christopher A. ; Rees, William. / Disruption of lipid metabolism in the liver of the pregnant rat fed folate-deficient and methyl donor-deficient diets. In: British Journal of Nutrition. 2008 ; Vol. 99, No. 2. pp. 262-271.
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AB - The importance of folic acid and the methionine cycle in fetal development is well recognised even though the mechanism has not been established. Since the cycle is active in the maternal liver, poor folate status may modify hepatic metabolism. Pregnant rats were fed diets deficient in folic acid (-F) or in three key methyl donors, folic acid, choline and methionine (-FLMLC) and the maternal liver was analysed on day 21 of gestation. Two-dimensional gel electrophoresis of soluble proteins identified differentially abundant proteins, which could be allocated into nine functional groups. Five involved in metabolic processes, namely, folate/methionine cycle, tyrosine metabolism, protein metabolism. energy metabolism and lipid metabolism, and three in cellular processes, namely, endoplasmic reticulum function, bile production and antioxidant defence. The mRNA for sterol regulatory element-binding protein-1c and acetyl-CoA carboxylase-1 (fatty acid synthesis) were decreased by both -F and -FLMLC diets. The mRNA for PPAR alpha. and PPAR gamma and carnitine palmitoyl transferase (fatty acid oxidation) were increased in the animals fed the -FLMLC diets. Changes in the abundance of proteins associated with intracellular lipid transport suggest that folate deficiency interferes with lipid export. Reduced fatty acid synthesis appeared to prevent steatosis in animals fed the -F diet. Even with increased oxidation, TAG concentrations were approximately three-fold higher in animals fed the -FLMLC diet and were associated with an increase in the relative abundance of proteins associated with oxidative stress. Fetal development may be indirectly affected by these changes in hepatic lipid metabolism.

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KW - disease

KW - mice

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