Serum metabolomics analysis reveals that weight loss in obese dogs results in a similar metabolic profile to dogs in ideal body condition

Abstract
Introduction The study of metabolic profile can be an important tool to better understand, at a systemic level, metabolic alterations caused by different pathological conditions, such as obesity. Furthermore, it allows the discovery of metabolic biomarkers, which may help to diagnose alterations caused by obesity. Objective To investigate the metabolic profile of blood serum of obese dogs, control dogs, and dogs that were subjected to a weight loss program. Methods Ten obese adult spayed female dogs were included, and their body composition was determined by the deuterium isotope dilution method. The dogs were subjected to a weight loss program and formed a new experimental group after losing 20% of the initial body weight. A third experimental group was composed of ten lean adult spayed female dogs. The metabolic profile of blood serum was evaluated through nuclear magnetic resonance (NMR). Principal Component Analyses (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) models were constructed using Pareto scaling pre-processing. Pathway analysis was also performed using the MetaboAnalist online tool. Results The PCA shows that the control and after weight loss groups presented a trend to negative PC1, indicating similarities between these two groups. In contrast, obese animals presented a tendency to appear on negative PC2 indicating a different metabolic profile. The OPLS-DA analysis of the serum indicated that healthy groups presented higher content of glucose, while animals that lost weight had higher levels of cholesterol and lactate than the control group. On the other hand, the analysis showed that lipid content, cholesterol, and branched-chain amino acids were highest in obese animals. Variable Influence on Projection (VIP) analysis demonstrated that Lactate is the most important metabolite for the OPLS-DA model and Hierarchical Cluster Analysis (HCA) corroborated the similarity between the control group and the obese after weight loss groups. Moreover, the pathway analysis indicated the most important metabolic pathways related to this dataset. Conclusions The metabolomic assessment based on NMR of blood serum differed between obese dogs and animals in optimal body condition. Moreover, the weight loss resulted in metabolic profiles similar to those observed in lean animals.