2172-LB: Assessing Glucose Homeostasis in Obesity Using Concurrent Arterial Glucose Telemetry and Indirect Calorimetry

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Introduction and Objective: Continuous blood glucose monitoring in mice using implantable telemetry devices is a highly sophisticated technique that measures real-time arterial blood glucose. This technique has not yet been combined with indirect calorimetry to study metabolism in obesity. By combining these techniques, this study was designed to gain a higher resolution understanding of the effect of obesity on glucose homeostasis. Methods: DSI HD-XG telemetry probes were surgically implanted into 22 week old C57Bl6/J chow or DIO mice (n=9 per group). After recovering for 7 days, mice underwent indirect calorimetry measurements in Promethion metabolic cages with various metabolic challenges including glucose and insulin tolerance tests, wheel running, 16 hour fast, and 6 hours of acute cold exposure at 6°C. Testing was then repeated including tail blood sampling. Results: As expected, both techniques detected major differences in the metabolic response to challenges to glucose homeostasis. These data also revealed clear artifacts of tail sampling artificially elevating blood glucose. Furthermore, it demonstrated the advantages of having concurrent indirect calorimetry and arterial glucose measurements providing high-resolution insights into the impact of activity and food intake on RER and blood glucose. Conclusion: This study integrated two highly sophisticated techniques to provide a high-resolution view of the effect of obesity on glucose homeostasis. Integration of these techniques to view the whole metabolic picture provided insights into metabolism and demonstrated the need to avoid artifacts of tail blood sampling. Future studies should focus on integrating sophisticated techniques while reducing the artifact of tail blood sampling to inform obesity research. Disclosure C.D. Holman: None. P.M. Titchenell: Consultant; Pfizer Inc, Unnatural Products Inc., Supercede, Pioneering Medicines, Boehringer-Ingelheim, Alnylam, OrsoBio. J.A. Baur: Research Support; Pfizer Inc, Calico, Metro Biotech. Board Member; Cytokinetics Inc. Research Support; Elysium. Consultant; Altimmune Inc. Funding The Rodent Metabolic Phenotyping Core (RRID: SCR_022427) is supported in part by National Institutes of Health (NIH) grant S10-OD025098, the Cox Institute, and the Institute for Diabetes, Obesity and Metabolism (Perelman School of Medicine, University of Pennsylvania).

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