TY - JOUR
T1 - Metabolomics Reveals Altered Hepatic Bile Acids, Gut Microbiome Metabolites, and Cell Membrane Lipids Associated with Marginal Vitamin A Deficiency in a Mongolian Gerbil Model
AU - La Frano, Michael R.
AU - Brito, Alex
AU - Johnson, Catherine M.
AU - Wilhelmson, Baylee
AU - Gannon, Bryan
AU - Fanter, Rob K.
AU - Pedersen, Theresa L.
AU - Tanumihardjo, Sherry A.
AU - Newman, John W.
N1 - Funding Information:
The authors give special thanks to Kelsey Degreef, Kelly Condron, Megan Hupp, Jun Kwon, Morgan MacNeill, Jordan Mathens, Keith Ou, Rebecca Pascuel, Shawn Richmond, and Candice Rodriguez for their contribution to the manuscript. The authors also thank Jerrad del Real for his assistance with figure illustrations. This study was funded by the Cal Poly College of Agriculture, Food and Environmental Sciences Summer Undergraduate Research Program (SURP). Additional support was provided by USDA Intramural Project 2032‐51530‐022‐00D and NIH U24 DK097154. The USDA is an equal opportunity employer and provider.
Funding Information:
The authors give special thanks to Kelsey Degreef, Kelly Condron, Megan Hupp, Jun Kwon, Morgan MacNeill, Jordan Mathens, Keith Ou, Rebecca Pascuel, Shawn Richmond, and Candice Rodriguez for their contribution to the manuscript. The authors also thank Jerrad del Real for his assistance with figure illustrations. This study was funded by the Cal Poly College of Agriculture, Food and Environmental Sciences Summer Undergraduate Research Program (SURP). Additional support was provided by USDA Intramural Project 2032-51530-022-00D and NIH U24 DK097154. The USDA is an equal opportunity employer and provider.
Publisher Copyright:
© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2020/7/1
Y1 - 2020/7/1
N2 - 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.
AB - 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.
KW - liver
KW - metabolomics
KW - nutritional metabolomics
KW - omics
KW - vitamin A
UR - http://www.scopus.com/inward/record.url?scp=85087208713&partnerID=8YFLogxK
U2 - 10.1002/mnfr.201901319
DO - 10.1002/mnfr.201901319
M3 - Article
C2 - 32453876
AN - SCOPUS:85087208713
SN - 1613-4125
VL - 64
JO - Molecular Nutrition and Food Research
JF - Molecular Nutrition and Food Research
IS - 13
M1 - 1901319
ER -