Plasma Metabolite Profiling and Search for Biomarkers of Metabolic Dysfunction in Dogs Undergoing Rapid Weight Gain

The objective of this experiment was to use untargeted plasma metabolite profiling to identify metabolite changes and potential biomarkers of metabolic dysfunction that accompanies rapid weight gain in dogs. Five intact female beagles were fed ad libitum for a period of 24 wk. Blood samples were collected after an overnight fast via jugular venipuncture at 0, 4, 8, 12, and 24 wk of feeding. Plasma was stored at -80°C until GC-MS and LC-MS-MS analyses. A total of 284 named biochemicals were identified, with as many as 175 metabolites being altered (p<0.05) at each time point. Principal component analysis (PCA) clearly indicated two distinct clusters over time during obesity development. The first, comprised of wk 0, 4, 8, and 12 (acute phase), and the second, comprised of wk 24 (chronic phase). Random forest (RF) analysis highlighted several metabolites having a high degree of predictive accuracy between acute and chronic phases. Of carbohydrate metabolism-related pathways, plasma mannose, citrate, and α-ketoglutarate seem to be promising biomarkers of chronic obesity. Metabolites associated with amino acid and lipid metabolism were drastically affected by weight gain and, in general, displayed a bi-phasic pattern with several plasma metabolites being increased during the acute phase and decreased at the chronic phase of weight accretion. At wk 24, lysophospholipids were increased, suggesting acylchain remodeling and potential phospholipid synthesis. Given the distinct metabolite profiles at wk 12 and 24, this study identified several potential biomarkers of metabolic dysfunction that develops with weight gain in dogs.