ICCFGG 2022
#33 A common canine POMC mutation increases obesity risk by affecting both hunger and metabolic rate Eleanor Raffan*, Marie Dittmann , Jodie Wainwright, Gabriella Lakatos, Stephen O’Rahilly, er311@cam.ac.uk Wellcome-MRC Institute of Metabolic Science, Metabolic Research Laboratories, University of Cambridge, UK. *Currently Dept Physiology, Development and Neuroscience, University of Cambridge, UK Background: We previously reported a mutation in the gene POMC that is common in Labrador and Flatcoated retriever dogs. The mutation is associated with increased adiposity, weight, and own- er-reported food motivation. POMC is central to the control of energy homeostasis and the variant provided an opportunity to study the effect of two of its derived neuroactive peptides, β -MSH and β -endorphin. We performed physiological studies that link the mutation to weight gain. Methods & Results : We recruited adult, healthy, lean pet dogs and tested their eating behaviour (in Labrador retrievers) and energy expenditure (in Flatcoat retrievers) in standardised conditions. Dogs heterozygous for the mutation had greater incentive salience in response to a food stimulus, interpreted as increased hunger. To test voluntary food intake, we presented dogs with a modified ad libitum meal. There was no significant difference in food intake between genotypes but vomiting or regurgitation was more common in wild type dogs at the end of the trial. We found no difference in the hedonic response to food. Resting energy expenditure was measured using indirect calorimetry in the post-absorptive state while dogs slept. Resting metabolic rate was markedly lower in dogs homozygous for the mutation than for wild type dogs. Conclusion: We have shown the physiological mechanisms linking a common canine mutation to increased obesity. As well as being of veterinary interest we provide insight into POMC biology and cement the value of dogs as a model organism since POMC derived neuropeptides are identical to those in humans, in contrast with rodent models. #34 The microenvironment of the bone marrow niche in Canine Osteosarcoma McKaela Hodge 1 , Tasha Miller 2 , Marcus Weinman 2 , Brandan Janssens 2 , Shay Bracha 2 , Brian W. Davis 1 , 2 mckaelaautumn19@tamu.edu 1 Department of Veterinary Integrative Biosciences, Texas A&M College of Veterinary Medicine and Biomedical Sciences, College Station, TX, USA, 2Department of Small Animal Clinical Sciences, Texas A&M College of Veterinary Medicine and Biomedical Sciences, College Station, TX, USA Canine osteosarcoma (OSA) prognosis has remained unchanged for the past three decades. Immunotherapy has improved many cancer outcomes but has been inapplicable to osteosarcoma because of its immune evasiveness and the immunosuppressive bone marrow microenvironment. Another challenge is the development of chemotherapeutic resistance in those malignant cells that survive treatment. The mechanisms of resistance acquisition and the manner of resistance conveyance to naive tumor cells are as-yet unknown. Extracellular vesicles termed exosomes are one potential method chemoresistant cells may convey this attribute to naïve cells. We used single
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