Metabolomics Reveals Altered Hepatic Bile Acids, Gut Microbiome Metabolites, and Cell Membrane Lipids Associated with Marginal Vitamin A Deficiency in a Mongolian Gerbil Model

Michael R. La Frano*, Alex Brito, Catherine M. Johnson, Baylee Wilhelmson, Bryan Gannon, Rob K. Fanter, Theresa L. Pedersen, Sherry A. Tanumihardjo, John W. Newman

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Scope: This study is designed to provide a broad evaluation of the impacts of vitamin A (VA) deficiency on hepatic metabolism in a gerbil model. Methods and results: After 28 days of VA depletion, male Mongolian gerbils (Meriones unguiculatus) are randomly assigned to experimental diets for 28 days. Groups are fed a white-maize-based diet with ≈50 µL cottonseed oil vehicle either alone (VA−, n = 10) or containing 40 µg retinyl acetate (VA+, n = 10) for 28 days. Liver retinol is measured by high-performance liquid chromatography. Primary metabolomics, aminomics, lipidomics, bile acids, oxylipins, ceramides, and endocannabinoids are analyzed in post-mortem liver samples by liquid chromatography–mass spectrometry. Results: Liver retinol is lower (p < 0.001) in the VA− versus VA+ group, with concentrations indicating marginal VA deficiency. A total of 300 metabolites are identified. Marginal VA deficiency is associated with lower bile acids, trimethylamine N-oxide, and a variety of acylcarnitines, phospholipids and sphingomyelins (p < 0.05). Components of DNA, including deoxyguanosine, cytidine, and N-carbomoyl-beta-alanine (p < 0.05), are differentially altered. Conclusions: Hepatic metabolomics in a marginally VA-deficient gerbil model revealed alterations in markers of the gut microbiome, fatty acid and nucleotide metabolism, and cellular structure and signaling.

Original languageEnglish
Article number1901319
JournalMolecular Nutrition and Food Research
Volume64
Issue number13
DOIs
Publication statusPublished - 1 Jul 2020

Keywords

  • liver
  • metabolomics
  • nutritional metabolomics
  • omics
  • vitamin A

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