title: Veterinary Medicine and Multi-Omics Research for Future Nutrition Targets: Metabolomics and Transcriptomics of the Common Degenerative Mitral Valve Disease in Dogs.
abstract: Canine degenerative mitral valve disease (DMVD) is the most common form of heart disease in dogs. The objective of this study was to identify cellular and metabolic pathways that play a role in DMVD by performing metabolomics and transcriptomics analyses on serum and tissue (mitral valve and left ventricle) samples previously collected from dogs with DMVD or healthy hearts. Gas or liquid chromatography followed by mass spectrophotometry were used to identify metabolites in serum. Transcriptomics analysis of tissue samples was completed using RNA-seq, and selected targets were confirmed by RT-qPCR. Random Forest analysis was used to classify the metabolites that best predicted the presence of DMVD. Results identified 41 known and 13 unknown serum metabolites that were significantly different between healthy and DMVD dogs, representing alterations in fat and glucose energy metabolism, oxidative stress, and other pathways. The three metabolites with the greatest single effect in the Random Forest analysis were γ-glutamylmethionine, oxidized glutathione, and asymmetric dimethylarginine. Transcriptomics analysis identified 812 differentially expressed transcripts in left ventricle samples and 263 in mitral valve samples, representing changes in energy metabolism, antioxidant function, nitric oxide signaling, and extracellular matrix homeostasis pathways. Many of the identified alterations may benefit from nutritional or medical management. Our study provides evidence of the growing importance of integrative approaches in multi-omics research in veterinary and nutritional sciences.
authors.affiliation: 1 Nestlé Purina Research , Saint Louis, Missouri.
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Li
authors.affiliation: 2 Cummings School of Veterinary Medicine, Tufts University , North Grafton, Massachusetts.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Freeman
authors.affiliation: 2 Cummings School of Veterinary Medicine, Tufts University , North Grafton, Massachusetts.
authors.forename: John E
authors.initials: JE
authors.lastname: Rush
authors.affiliation: 3 MCRI Center for Translational Genomics, Molecular Cardiology Research Institute, Tufts Medical Center, and Tufts University School of Medicine , Boston, Massachusetts.
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Huggins
authors.affiliation: 4 Metabolon, Inc. , Durham, North Carolina.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Kennedy
authors.affiliation: 1 Nestlé Purina Research , Saint Louis, Missouri.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Labuda
authors.affiliation: 1 Nestlé Purina Research , Saint Louis, Missouri.
authors.forename: Dorothy P
authors.initials: DP
authors.lastname: Laflamme
authors.affiliation: 1 Nestlé Purina Research , Saint Louis, Missouri.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Hannah
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003663:Decision Trees; D004151:Dipeptides / Q000097:blood; D004285:Dogs; D019803:Glutathione Disulfide / Q000097:blood; D006349:Heart Valve Diseases / Q000097:blood* / Q000473:pathology / Q000662:veterinary*; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing / Q000662:veterinary; D050356:Lipid Metabolism; D055432:Metabolomics / Q000706:statistics & numerical data*; D008943:Mitral Valve / Q000378:metabolism* / Q000473:pathology; D058977:Molecular Sequence Annotation; D015596:Nutrition Assessment; D018384:Oxidative Stress; D011897:Random Allocation; D059467:Transcriptome
chemical_list: D001786:Blood Glucose; D004151:Dipeptides; C406458:glutamylmethionine; C018524:N,N-dimethylarginine; D001120:Arginine; D019803:Glutathione Disulfide