Metabolic Profiling Reveals Effects of Age, Sexual Development and Neutering in Plasma of Young Male Cats

Abstract

Neutering is a significant risk factor for obesity in cats. The mechanisms that promote neuter-associated weight gain are not well understood but following neutering, acute changes in energy expenditure and energy consumption have been observed. Metabolic profiling (GC-MS and UHPLC-MS-MS) was used in a longitudinal study to identify changes associated with age, sexual development and neutering in male cats fed a nutritionally-complete dry diet to maintain an ideal body condition score. At eight time points, between 19 and 52 weeks of age, fasted blood samples were taken from kittens neutered at either 19 weeks of age (Early Neuter (EN), n = 8) or at 31 weeks of age (Conventional Neuter (CN), n = 7). Univariate and multivariate analyses were used to compare plasma metabolites (n = 370) from EN and CN cats. Age was the primary driver of variance in the plasma metabolome, including a developmental change independent of neuter group between 19 and 21 weeks in lysolipids and fatty acid amides. Changes associated with sexual development and its subsequent loss were also observed, with differences at some time points observed between EN and CN cats for 45 metabolites (FDR p<0.05). Pathway Enrichment Analysis also identified significant effects in 20 pathways, dominated by amino acid, sterol and fatty acid metabolism. Most changes were interpretable within the context of male sexual development, and changed following neutering in the CN group. Felinine metabolism in CN cats was the most significantly altered pathway, increasing during sexual development and decreasing acutely following neutering. Felinine is a testosterone-regulated, felid-specific glutathione derivative secreted in urine. Alterations in tryptophan, histidine and tocopherol metabolism observed in peripubertal cats may be to support physiological functions of glutathione following diversion of S-amino acids for urinary felinine secretion.

Docosahexaenoate-enriched fish oil and medium chain triglycerides shape the feline plasma lipidome and synergistically decrease circulating gut microbiome-derived putrefactive postbiotics

“…Genomic investigations have recently characterized genetic elements associated with domestication of the housecat (Felis catus) compared with wildcats and found genes involved in lipid metabolism to be altered, including representatives of the fatty acid beta oxidation, ether lipid metabolism, and peroxisomal lipid metabolism pathways [30]. A few published studies have characterized the feline circulating metabolome [31][32][33], however, without specific focus on lipids. The levels and types of circulating complex lipid classes are not extensively documented in the cat.…”

The impact of time of neutering on weight gain and energy intake in female kittens

“…In addition to the TER study reported here, a parallel TER study in male kittens (also neutered at 19 weeks compared with a control group that remained entire to 31 weeks of age) observed no significant increase in mean average daily energy intake (kcal/kg BW 0·67 ) ( 17 ) . However, following neutering at 31 weeks a significant difference in intake (CN group being greater, up to 36 (95 % CI 9, 62) kcal/kg BW 0·67 (151 (95 % CI 38, 259) kJ/kg BW 0·67 ) was observed between the two groups in weeks 34–36 and weeks 38–41, consistent with other reports in adult male cats 2·5–3·6 years of age), where an immediate and significant increase in food intake from 3 to 19 weeks post-procedure was observed ( 18 ) .…”

Soy-Induced Fecal Metabolome Changes in Ovariectomized and Intact Female Rats: Relationship with Cardiometabolic Health

“…In male cats, sexual maturity and age at time of neutering, i.e. removal of ovarian steroid hormones, can affect circulating metabolites 42 .…”