Premium
Metabolomics Reveals Altered Hepatic Bile Acids, Gut Microbiome Metabolites, and Cell Membrane Lipids Associated with Marginal Vitamin A Deficiency in a Mongolian Gerbil Model
Author(s) -
La Frano Michael R.,
Brito Alex,
Johnson Catherine M.,
Wilhelmson Baylee,
Gan Bryan,
Fanter Rob K.,
Pedersen Theresa L.,
Tanumihardjo Sherry A.,
Newman John W.
Publication year - 2020
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201901319
Subject(s) - metabolomics , medicine , biochemistry , metabolism , endocrinology , lipid metabolism , gerbil , bile acid , retinol , orotic acid , biology , chemistry , vitamin , chromatography , ischemia
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.