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

doi:10.1002/mnfr.201901319

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

Mol Nutr Food Res. 2020 Jul;64(13):e1901319. doi: 10.1002/mnfr.201901319. Epub 2020 Jun 22.

Authors

Michael R La Frano^{1

2

3

4}, Alex Brito^{5

6}, Catherine M Johnson¹, Baylee Wilhelmson¹, Bryan Gannon^{7

8}, Rob K Fanter⁹, Theresa L Pedersen¹⁰, Sherry A Tanumihardjo⁷, John W Newman^{3

4

11}

Affiliations

¹ Department of Food Science and Nutrition, California Polytechnic State University, San Luis Obispo, CA, 93407, USA.
² Center for Health Research, California Polytechnic State University, San Luis Obispo, CA, 93407, USA.
³ West Coast Metabolomics Center, University of California, Davis, CA, USA.
⁴ Department of Nutrition, University of California Davis, Davis, CA, USA.
⁵ Laboratory of Pharmacokinetics and Metabolomic Analysis, Institute of Translational Medicine and Biotechnology, I. M. Sechenov First Moscow State Medical University, Moscow, 119991, Russia.
⁶ Luxembourg Institute of Health, Department of Population Health, Nutrition and Health Research Group, 1A-B, rue Thomas Edison, Strassen, 1445, Luxembourg.
⁷ University of Wisconsin-Madison, Department of Nutritional Sciences, Madison, WI, USA.
⁸ Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA.
⁹ College of Agriculture, Food and Environmental Sciences, California Polytechnic State University, San Luis Obispo, CA, USA.
¹⁰ Department of Food Science and Technology, University of California Davis, Davis, CA, USA.
¹¹ Obesity and Metabolism Research Unit, United States Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center, Davis, CA, USA.

PMID: 32453876
DOI: 10.1002/mnfr.201901319

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.

Keywords: liver; metabolomics; nutritional metabolomics; omics; vitamin A.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Animals
Bile Acids and Salts / metabolism*
Ceramides / metabolism
Data Visualization
Disease Models, Animal
Gastrointestinal Microbiome / physiology*
Gerbillinae
Liver / drug effects
Liver / metabolism*
Male
Membrane Lipids / metabolism
Metabolomics / methods
Vitamin A / blood
Vitamin A / pharmacology
Vitamin A Deficiency / metabolism*
Vitamin A Deficiency / microbiology

Substances

Bile Acids and Salts
Ceramides
Membrane Lipids
Vitamin A

Grants and funding

U24 DK097154/DK/NIDDK NIH HHS/United States