Dietary modulation of canine metabolism for obesity management and cancer risk reduction

Abstract

Metabolic aberrancies associated with environmental exposures and excess adiposity can increase risk for multiple chronic diseases. Obesity is the primary nutritional disorder of companion dogs and incidence and prevalence rates continue to increase, yet little is known about underlying metabolic disruption in obese dogs or the role of environmental contaminants to which companion dogs are exposed. Cooked common beans (Phaseolus vulgaris, L.) are a rich source of macro-, micro-, and phytonutrients that have potential to support healthy weight management in dogs, modulate metabolism, and decrease risk for chronic disease, but have yet to be evaluated for safety and digestibility in dogs. Given the prevalence of obesity in companion dogs and the potential of bean consumption to improve health, the overarching hypothesis for this dissertation is that cooked beans are well tolerated and palatable in dog food and beneficially modulate underlying metabolic pathways associated with canine obesity and environmental exposures. The major objectives in this dissertation were to 1) determine environmental exposures and obesity associated metabolic aberrancies in companion dogs; 2) investigate the feasibility, safety and digestibility of incorporating cooked bean powders into nutritionally complete dog food formulations; and 3) determine the effects of weight loss and bean intake on metabolic parameters. To accomplish these objectives, 66 clinically healthy, adult companion dogs of various breeds and genders were recruited to participate in randomized, controlled bean-based dietary intervention studies performed at Colorado State University Veterinary Teaching Hospital and Wellington Animal Hospital. The specific hypotheses tested were: • Companion dogs are exposed to detectable levels of environmental pollutants and exhibit altered metabolomes associated with obesity. • Dry dog foods formulated with 25 % weight/weight cooked bean powders are safe, digestible, and well tolerated compared to a nutrient matched control diet. • Dogs consuming bean-based diets will have altered lipid and carbohydrate metabolism, reduced inflammation, increased expression of satiety gut hormones, and decreased insulin resistance. We first determined the background exposures to pesticides as detected in urine from 21 normal weight dogs. Urine samples collected from the dogs were screened for a panel of 301 pesticides using an established ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) platform. Fifteen distinct pesticides were detected: the most frequently detected compounds in canine urine were atrazine, fuberidazole, imidacloprid, terbumeton, and clopyralid. We next evaluated 66 clinically healthy dogs that were normal weight, overweight, or obese for differences in serum biochemistry, microbiome, and metabolome. The proportion of overweight and obese dogs with hemolysis, creatinine kinase, and aspartate aminotransferase (AST) levels outside reference ranges was higher than normal weight dogs. Levels of AST, chloride, and gamma-glutamyl transpeptidase were lower in overweight or obese dogs. The fecal microbiomes were evaluated in a subset of 50 dogs using 16S Illumina based sequencing. The fecal microbiome comprised, in order of abundance, the phyla Firmicutes, Bateroidetes, Proteobacteria, and Actinobacteria. Significant variation existed between all dogs with no differences found at the level of phyla, class, order, family, or genus level. The fecal, plasma, and urine metabolome of 66 dogs were evaluated by liquid chromatography (LC) and gas chromatography coupled to mass spectrometry (MS), and 266 compounds were differentially expressed by weight phenotype. Difference in plasma metabolites accounted for 44 % of the variation between normal weight, overweight, and obese dogs. To determine the safety and digestibility of incorporating cooked bean powders into nutritionally complete dog foods, three clinical trials were carried out. Dogs consuming bean-based diets maintained indices of adequate nutritional intake as mandated by the Association of American Feed Control Officials (AAFCO) feeding trials. Bean-based diets were as digestible as the matched, standard ingredient, control (CON) dog foods. In overweight dogs undergoing weight loss, the black bean (BB) diet had higher total dry matter and crude protein digestibility and both the navy bean (NB) and black bean diets had higher carbohydrate digestibility than the CON diet. No increased flatulence or major change in fecal consistency was reported by any of the owners for any dogs. Normal weight dogs consuming beans had lower serum cholesterol levels than the CON dogs, and dogs undergoing weight loss on bean-based diets had decreases in serum HDL, LDL, and triglycerides. Metabolites associated with lipid, carbohydrate, and protein metabolism were altered in bean consuming dogs; however in dogs undergoing weight loss, the greatest shift in the metabolome was observed in response to weight loss, independent of diet. This work highlights the utility of metabolomic platforms for evaluating the metabolism of dogs and determining intervention responsive metabolic pathways. These data provide a foundation for continued investigation into the role of beans for healthy weight management and obesity and cancer prevention in dogs.