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

Authors: SMITH, CAREN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; Parnell, Laurence; Lai, Chao Qiang; RUSH, JOHN - Tufts University; ADIN, DARCY - University Of Florida; ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; FREEMAN, LISA - Tufts University

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/13/2022
Publication Date: 12/30/2022
Citation: Smith, C.E., Parnell, L.D., Lai, C., Rush, J.E., Adin, D.B., Ordovas, J.M., Freeman, L.M. 2022. Metabolomic profiling in dogs with dilated cardiomyopathy eating non-traditional or traditional diets and in healthy controls. Scientific Reports. https://doi.org/10.1038/s41598-022-26322-8.
DOI: https://doi.org/10.1038/s41598-022-26322-8

Interpretive Summary: Dilated cardiomyopathy (DCM) is a leading contributor to heart failure, which occurs with a higher incidence in older populations. Mechanisms that differentiate the primary or genetics-based form of this disease versus any of a number of secondary factors, such as drug treatment, diet or environmental toxins, remain incompletely described. Hence, building upon our previous work that examined the chemical composition of diets that were associated with higher DCM occurrence, we analyzed a large number of metabolic factors in blood of pet dogs either healthy or diseased hearts, and fed either of the two diet types. These analyses revealed a number of biological processes that contribute to diet-related DCM, many of which are distinct from primary DCM. Some of these processes involve inflammation and oxidative damage, and together with a set of metabolic factors unique to diet-associated DCM (including molecules that are fuel for the heart muscle), highlight the paths by which diet can lead to this debilitating disease.

Technical 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 17 metabolites differed significantly between dogs with DCM vs. healthy controls and dogs eating NT vs. 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 vs. traditional diets (e.g., fatty acids, amino acids, legume biomarkers), suggesting different mechanisms for primary vs. diet-associated DCM. Our multifaceted metabolomic assessment of DCM in dogs highlighted diet's role in some forms of DCM.