Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls

Abstract Dilated cardiomyopathy (DCM), caused by genetic and environmental factors, usually progresses to heart failure, a major cause of death in elderly people. A diet-associated form of DCM was recently identified in pet dogs eating non-traditional (NT) diets. To identify potential dietary causes...

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Main Authors: Caren E. Smith, Laurence D. Parnell, Chao-Qiang Lai, John E. Rush, Darcy B. Adin, José M. Ordovás, Lisa M. Freeman
Format: Article
Language:English
Published: Nature Portfolio 2022-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-26322-8
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author Caren E. Smith
Laurence D. Parnell
Chao-Qiang Lai
John E. Rush
Darcy B. Adin
José M. Ordovás
Lisa M. Freeman
author_facet Caren E. Smith
Laurence D. Parnell
Chao-Qiang Lai
John E. Rush
Darcy B. Adin
José M. Ordovás
Lisa M. Freeman
author_sort Caren E. Smith
collection DOAJ
description Abstract Dilated cardiomyopathy (DCM), caused by genetic and environmental factors, usually progresses to heart failure, a major cause of death in elderly people. A diet-associated form of DCM was recently identified in pet dogs eating non-traditional (NT) diets. To identify potential dietary causes, we analyzed metabolomic signatures and gene set/pathway enrichment in (1) all dogs based on disease, diet, and their interactions and (2) dogs with DCM based on diet. Metabolomic analysis was performed in 38 dogs with DCM eating NT diets (DCM-NT), 8 dogs with DCM eating traditional diets, 12 healthy controls eating NT diets, and 17 healthy controls eating traditional diets. Overall, 153 and 63 metabolites differed significantly between dogs with DCM versus healthy controls and dogs eating NT versus traditional diets, respectively, with 12 metabolites overlapping both analyses. Protein–protein interaction networks and gene set enrichment analysis identified 105 significant pathways and gene sets including aging-related pathways (e.g., nuclear factor-kappa B, oxidative damage, inflammation). Seventeen metabolites differed significantly in dogs with DCM eating NT versus traditional diets (e.g., fatty acids, amino acids, legume biomarkers), suggesting different mechanisms for primary versus diet-associated DCM. Our multifaceted metabolomic assessment of DCM in dogs highlighted diet’s role in some forms of DCM.
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spelling doaj.art-b4e14189d89842448fd7af3d88bcaa542023-01-01T12:18:36ZengNature PortfolioScientific Reports2045-23222022-12-0112111410.1038/s41598-022-26322-8Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controlsCaren E. Smith0Laurence D. Parnell1Chao-Qiang Lai2John E. Rush3Darcy B. Adin4José M. Ordovás5Lisa M. Freeman6Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityUSDA Agricultural Research Service, Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityUSDA Agricultural Research Service, Nutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityDepartment of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts UniversityDepartment of Large Animal Clinical Sciences, University of Florida, College of Veterinary MedicineNutrition and Genomics Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts UniversityDepartment of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts UniversityAbstract Dilated cardiomyopathy (DCM), caused by genetic and environmental factors, usually progresses to heart failure, a major cause of death in elderly people. A diet-associated form of DCM was recently identified in pet dogs eating non-traditional (NT) diets. To identify potential dietary causes, we analyzed metabolomic signatures and gene set/pathway enrichment in (1) all dogs based on disease, diet, and their interactions and (2) dogs with DCM based on diet. Metabolomic analysis was performed in 38 dogs with DCM eating NT diets (DCM-NT), 8 dogs with DCM eating traditional diets, 12 healthy controls eating NT diets, and 17 healthy controls eating traditional diets. Overall, 153 and 63 metabolites differed significantly between dogs with DCM versus healthy controls and dogs eating NT versus traditional diets, respectively, with 12 metabolites overlapping both analyses. Protein–protein interaction networks and gene set enrichment analysis identified 105 significant pathways and gene sets including aging-related pathways (e.g., nuclear factor-kappa B, oxidative damage, inflammation). Seventeen metabolites differed significantly in dogs with DCM eating NT versus traditional diets (e.g., fatty acids, amino acids, legume biomarkers), suggesting different mechanisms for primary versus diet-associated DCM. Our multifaceted metabolomic assessment of DCM in dogs highlighted diet’s role in some forms of DCM.https://doi.org/10.1038/s41598-022-26322-8
spellingShingle Caren E. Smith
Laurence D. Parnell
Chao-Qiang Lai
John E. Rush
Darcy B. Adin
José M. Ordovás
Lisa M. Freeman
Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls
Scientific Reports
title Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls
title_full Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls
title_fullStr Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls
title_full_unstemmed Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls
title_short Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls
title_sort metabolomic profiling in dogs with dilated cardiomyopathy eating non traditional or traditional diets and in healthy controls
url https://doi.org/10.1038/s41598-022-26322-8
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