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Sex-Specific Metabolic Effects of Dietary Folate Withdrawal in Wild-Type and Aldh1l1 Knockout Mice.
Sharma, Jaspreet; Rushing, Blake R; Hall, Madeline S; Helke, Kristi L; McRitchie, Susan L; Krupenko, Natalia I; Sumner, Susan J; Krupenko, Sergey A.
Afiliação
  • Sharma J; Nutrition Research Institute, UNC Chapel Hill, Kannapolis, NC 28081, USA.
  • Rushing BR; Nutrition Research Institute, UNC Chapel Hill, Kannapolis, NC 28081, USA.
  • Hall MS; Department of Nutrition, UNC Chapel Hill, Chapel Hill, NC 27599, USA.
  • Helke KL; Nutrition Research Institute, UNC Chapel Hill, Kannapolis, NC 28081, USA.
  • McRitchie SL; Department of Nutrition, UNC Chapel Hill, Chapel Hill, NC 27599, USA.
  • Krupenko NI; Department of Comparative Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
  • Sumner SJ; Nutrition Research Institute, UNC Chapel Hill, Kannapolis, NC 28081, USA.
  • Krupenko SA; Nutrition Research Institute, UNC Chapel Hill, Kannapolis, NC 28081, USA.
Metabolites ; 12(5)2022 May 18.
Article em En | MEDLINE | ID: mdl-35629957
ALDH1L1 (10-formyltetrahydrofolate dehydrogenase), an enzyme of folate metabolism, is highly expressed in the liver. It regulates the overall flux of folate-bound one-carbon groups by converting 10-formyltetrahydrofolate to tetrahydrofolate and CO2 in a NADP+-dependent reaction. Our previous study revealed that Aldh1l1 knockout (KO) mice have an altered liver metabotype with metabolic symptoms of folate deficiency when fed a standard chow diet containing 2 ppm folic acid. Here we performed untargeted metabolomic analysis of liver and plasma of KO and wild-type (WT) male and female mice fed for 16 weeks either standard or folate-deficient diet. OPLS-DA, a supervised multivariate technique that was applied to 6595 and 10,678 features for the liver and plasma datasets, respectively, indicated that genotype and diet, alone or in combination, gave distinct metabolic profiles in both types of biospecimens. A more detailed analysis of affected metabolic pathways based on most confidently identified metabolites in the liver and plasma (OL1 and OL2a ontology level) indicated that the dietary folate restriction itself does not fully recapitulate the metabolic effect of the KO. Of note, dietary folate withdrawal enhanced the metabolic perturbations linked to the ALDH1L1 loss only for a subset of metabolites. Importantly, both the ALDH1L1 loss and dietary folate deficiency produced sex-specific metabolic effects.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Metabolites Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Idioma: En Revista: Metabolites Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Estados Unidos