Obesity affects around 45% of domestic cats, and licensed drugs for treating feline obesity are lacking. Physical exercise and calorie restrictions are commonly used for weight loss but with limited efficacy.

Background Fecal specimens are critical for disease screening, diagnosis, and gut microbiome research. For domestic cats, lubricants are often necessary to obtain a sufficient quantity of sample. However, the effect of lubrication on feline microbiome analysis has not been assessed. Objectives To evaluate if lubrication using mineral oil during cat feces sample collection affects the DNA extraction, metagenomic sequencing yield, and the microbial composition and diversity in subsequent gut microbiome analyses. Animals Eight 6‐year‐old male, neutered, domestic short‐haired cats housed in a research facility. Methods Cohort study. The gut microbiomes were investigated for fecal sample collection with and without lubrication using whole‐genome shotgun metagenomic sequencing. Results Fecal specimens were collected using a fecal loop under sedation without lubrication and with mineral oil lubrication. There were no significant differences between the 2 groups in the microbial DNA yield in ng/mg fecal sample (75.75 [25.8‐125.7] vs 60.72 [33.49‐87.95], P = .95), metagenomic sequencing yield in Gbp (10.31 [6.29‐14.32] vs 13.53 [12.04‐15.02], P = .2), proportion of host contamination (0.1 [0.02‐0.18] vs 0.15 [0‐0.3], P = .84), relative taxonomy abundance (P > .8), or the number of microbial genes covered (408 132 [341 556‐474 708] vs 425 697 [358 505‐492 889], P = .31). Conclusions and Clinical Importance Fecal sampling with mineral oil lubrication did not change the microbial DNA extraction yield, metagenomic sequencing yield, level of host contamination, the microbial composition and diversity in subsequent gut microbiome analyses. Here we reported a proven cat‐friendly protocol for fecal sample collection in clinical and research setting for gut microbiome analyses.

IntroductionFeline obesity is common, afflicting ~25–40% of domestic cats. Obese cats are predisposed to many metabolic dyscrasias, such as insulin resistance, altered blood lipids, and feline hepatic lipidosis. Fibroblast Growth Factor-21 (FGF21) is an endocrine hormone that mediates the fat-liver axis, and in humans and animals, FGF21 can ameliorate insulin resistance, non-alcoholic fatty liver disease, and obesity. Activation of the FGF21 pathway may have therapeutic benefits for obese cats.MethodsIn this preliminary cross-sectional study, ad libitum fed, purpose-bred, male-neutered, 6-year-old, obese and overweight cats were administered either 10 mg/kg/day of an FGF21 mimetic (FGF21; n = 4) or saline (control; n = 3) for 14 days. Body weight, food, and water intake were quantified daily during and 2 weeks following treatment. Changes in metabolic and liver parameters, intrahepatic triglyceride content, liver elasticity, and gut microbiota were evaluated.ResultsTreatment with FGF21 resulted in significant weight loss (~5.93%) compared to control and a trend toward decreased intrahepatic triglyceride content. Cats treated with FGF21 had decreased serum alkaline phosphatase. No significant changes were noted in liver elasticity, serum, liver, or metabolic parameters, or gut microbiome composition.DiscussionIn obese and overweight cats, activation of the FGF21 pathway can safely induce weight loss with trends to improve liver lipid content. This exploratory study is the first to evaluate the FGF21 pathway in cats. Manipulation of the FGF21 pathway has promising potential as a therapeutic for feline obesity. Further studies are needed to see if FGF21-pathway manipulation can be therapeutic for feline hepatic lipidosis.

In collaboration with the American College of Veterinary Pathologists

Hydroxycarboxylic acid receptor 2 (HCA2) , formally known as GPR109A, is a metabolite-sensing receptor expressed predominately on adipocytes, immune cells and intestinal epithelial cells. The primary endogenous ligand of HCA2 is β-hydroxybutyrate (βOHB) , which is elevated during periods of nutrient deprivation including fasting. Previous in vitro studies have suggested that βOHB activation of HCA2 on adipocytes inhibits lipolysis and serves as a negative feedback mechanism to prevent excess fat loss during fasting. However, the metabolic implications of this feedback mechanism have not been tested in vivo during a prolonged fast. To address this question, male and female C57BL/6J (WT) and HCA2 knockout (KO) mice were fasted in metabolic cages for 36 hours. No significant differences were observed for genotype or sex in RER, EE, or VO2. Following the fast, KO males exhibited a significant decrease in body weight compared to their WT counterparts. However, body weight was not significantly different between female WT and KO mice after fasting. Gonadal white adipose tissue (gWAT) depot weights were significantly lower in KO male mice compared to WT male mice, with no significant difference in gWAT weight between female WT and KO mice. Inguinal white adipose tissue (iWAT) depot weights were significantly lower for both sexes in KO mice compared to WT mice. KO males displayed significantly lower levels of circulating NEFAs compared to WT males. However, no differences in NEFAs were observed between female WT and KO mice. No significant differences were shown between groups for glucose, insulin, or βOHB. Therefore, this study demonstrates that mice lacking HCA2 possess a diminished capacity to regulate body and adipose tissue weight during a fast, which is observed to a greater extent in male mice. Disclosure K.J.Mccafferty: None. E.Brinker: None. E.Graff: None. T.D.Steury: None. M.W.Greene: None. R.L.Judd: None.