Dynamic shifts in the serum lipidome of dogs with obesity before and after weight loss: a pilot study

Canine obesity is associated with metabolic disturbances, but specific lipid alterations remain poorly characterized. This study aimed to characterize the serum lipidome of dogs with obesity before and after weight loss and to identify lipid species and pathways associated with lipidomic remodeling following weight loss. Eight neutered dogs with obesity (four males and four females; 5.37 ± 1.41 years; 27.15 ± 12.02 kg; body condition score 9/9) were fed a commercial weight-loss diet. After a 3-week adaptation, blood was collected for lipidomic analysis before weight loss (OB). A weight-loss program was implemented for up to 6 months until dogs achieved a 20% reduction from initial body weight, followed by a second blood collection after weight loss (WL). Targeted lipidomic profiling was performed using two multiple reaction monitoring (MRM) methods on a triple quadrupole mass spectrometer, covering 3,437 lipid ion transitions. Data were processed in MetaboAnalyst 6.0 and analyzed using Student's t-test, volcano plot, partial least squares-discriminant analysis (PLS-DA), variable importance in projection (VIP) scoring, and Lipid Ontology (LION) enrichment analysis. Dogs achieved a total weight loss of 23.68 ± 3.18%, with a weekly rate of 1.01 ± 0.26%. A total of 630 lipid species were identified, and clear remodeling of the canine serum lipidome was observed following weight loss. Before weight loss, dogs had higher serum concentrations of cholesterol esters (P = 0.047), phosphatidylcholines (P = 0.043), phosphatidylinositols (P = 0.038), and sphingomyelins (P = 0.023) than after weight loss. At the individual lipid-species level, volcano plot analysis identified 34 differentially abundant lipid species before and after weight loss, including specific triglyceride, phospholipid, and cholesterol ester species. PLS-DA clearly discriminated the serum lipidomic profiles before and after weight loss with high predictive performance. Additionally, LION enrichment analysis revealed multiple significantly enriched terms related to lipid cellular components, functional roles, and physicochemical properties. These findings provide novel insights into serum lipidomic remodeling associated with weight loss in dogs with obesity and highlight lipid species potentially involved in the metabolic response to weight reduction.