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Theses and Dissertations

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Browsing Theses and Dissertations by Author "Avery, Anne C., committee member"

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    ItemOpen Access
    Dietary modulation of canine metabolism for obesity management and cancer risk reduction
    (Colorado State University. Libraries, 2015) Forster, Genevieve Michele, author; Ryan, Elizabeth P., advisor; Page, Rodney L., committee member; Bauer, John E., committee member; Avery, Anne C., committee member
    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.
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    ItemOpen Access
    Regulatory T cells in canine cancer
    (Colorado State University. Libraries, 2011) Burton, Jenna Hart, author; Biller, Barbara J., advisor; Avery, Anne C., committee member; Dow, Steven W., committee member; Thamm, Douglas H., committee member
    Numbers of regulatory T cells (Treg) are increased in some human malignancies and are often negatively correlated with patient disease-free interval and survival. Canine Treg have previously been identified in healthy and cancer-bearing dogs and have found to be increased in the blood of dogs with some types of cancer. Moreover, some preliminary research indicates that increased numbers of Treg and decreased numbers of CD8+ T cells in the blood of dogs with osteosarcoma (OSA) are associated with decreased survival. The aim of this project was to examine Treg distributions in dogs with cancer compared to normal dogs and to determine any association between Treg numbers and patient outcome. Additionally, we sought to determine if treatment with daily low-dose (metronomic) chemotherapy would decrease Treg in dogs with cancer. Pre-treatment Treg populations in blood, tumors, and lymph nodes of dogs with OSA were assessed and compared with Treg in blood and lymph nodes of a healthy, control population of dogs. No significant changes in Treg numbers in the blood or lymph nodes of the OSA-bearing dogs compared to the control population were identified. The dogs with OSA with treated with amputation of the affected limb followed by adjunctive chemotherapy. Treg numbers in the blood or tumor were not associated with outcome but an elevated ratio of CD8+ T cells to Treg in the tumor was associated with a prolonged disease-free interval and increased survival. These findings suggest that changes in number of Treg and effector T cell subset may provide prognostic information for canine OSA. In mice and humans with advanced cancer, the administration of metronomic (daily low dose) cyclophosphamide (CYC) selectively decreases circulating Treg numbers and inhibits their function. Protocols containing metronomic CYC likely have anti-tumor properties in dogs as well. Despite wide use of metronomic CYC in veterinary medicine, its effects on canine Treg have not previously been reported. Dogs with soft tissue sarcoma (STS) were administered CYC at 12.5 mg/m2 or 15 mg/m2 orally once daily for 28 days. Whole blood samples and tumor biopsies were obtained on days 0, 14, and 28 to assess changes in T lymphocyte subsets, circulating endothelial cells, and tumor microvessel density (MVD). Administration of CYC at 12.5 mg/m2/day significantly decreased the number of Treg from day 0 to 28, but there was no change in the percentage of Treg or tumor MVD. In dogs that received CYC at 15.0 mg/m2/day, both the number and percent of Treg as well as tumor MVD were significantly decreased over 28 days. These findings suggest that metronomic dosing of CYC may have immunomodulatory and antiangiogenic effects in dogs with cancer. Taken together the work described in this thesis support the theory that Treg are altered in dogs with cancer and that these changes may have prognostic value. Additionally, Treg can be decreased in dogs with cancer though administration of metronomic doses of CYC; the therapeutic benefit of Treg depletion has yet to be evaluated in cancer bearing dogs.