Modern bomb calorimeter for accurate determination of energy balance in metabolic studies

本提案的申请人在啮齿动物生理学，代谢和细胞信号传导领域进行前沿的基础研究。迄今为止的研究已经调查了基因、饮食和药理学操作如何影响全身能量平衡。我们nserc资助的研究项目的关键是测量能量平衡的能力。通过实验饮食的热量含量可以直接确定动物消耗的能量，通过使用代谢笼可以很容易地测量能量消耗，代谢笼可以深入了解动物使用的燃料来源（脂肪和碳水化合物）、产热和身体活动。然而，在这种简化的全身能量平衡观点中有一个基本的疏忽。事实上，我们假设啮齿动物消耗的所有卡路里都被吸收了（即完全消化效率）。这种假设是有缺陷的，可能导致对全身能量平衡数据的重大误解。为了解决这一重大缺口，我们正在申请资金购买最先进的炸弹量热计，以精确测量粪便的能量含量——这是消化效率的直接衡量标准。目前圭尔夫大学有一个热量计；然而，该系统位于另一个部门，被那些研究小组大量使用，已有20多年的历史，由于频繁故障而不可靠，并且由于用户之间的高度可变性而手动操作。因此，我们迫切需要一种现代炸弹量热计，它提供更高的精度，更高的吞吐量，并可供我们部门的研究人员使用。由于申请人和用户所涵盖的研究领域范围广泛，获得新的量热计的影响是显著的。例如，测量消化效率将导致我们如何解释食物摄入和能量平衡数据的根本和重要的变化，增强我们对控制消化效率的遗传和分子机制的认识，提高我们对饮食和药物干预如何影响体重调节的理解，并开辟新的研究途径。无法测量消化效率意味着我们的数据解释目前可能存在缺陷，我们正在失去揭示与体重调节相关的新分子机制的机会。预计获得一台现代量热计将在6个nserc资助的实验室中每年增加约50名高素质人员（HQP）的直接培训。总的来说，我们预计获得热量计将对许多nserc资助的研究项目产生直接和显著的好处，并将直接提高HQP的生产力和培训。

The applicants of this proposal conduct leading-edge basic research in the fields of rodent physiology, metabolism, and cell signalling. Studies to date have investigated how genetic, dietary, and pharmacological manipulations influence whole-body energy balance. Critical to our NSERC-funded research programs is the ability to measure energy balance. Determining the amount of energy consumed by an animal is straightforward from the caloric content of experimental diets and determining energy expenditure is easily measured through the use of metabolic cages, which provide insight regarding the fuel sources used by an animal (fat and carbohydrates), heat production, and physical activity. However, there is a fundamental oversight in this simplified view of whole-body energy balance. Indeed, we assume that all of the calories consumed by a rodent are absorbed (i.e., complete digestive efficiency). This assumption is flawed and can lead to important misinterpretations of whole-body energy balance data. To address this critical gap, we are requesting funds to purchase a state-of-the-art bomb calorimeter to precisely measure fecal energy content – which is a direct measure of digestive efficiency. There is currently one calorimeter located at the University of Guelph; however, this system is located in another department and is highly used by those research groups, is more than 20-years old, is unreliable due to frequent break-downs, and is manually operated leading to high variability between users. Thus we are in urgent need of a modern bomb calorimeter that provides greater accuracy, higher through-put and is accessible to researchers in our department. The impact of acquiring a new calorimeter is significant due to the wide-range of research areas covered by the applicants and users. For example, measuring digestive efficiency will lead to fundamental and important changes in how we interpret food intake and energy balance data, enhance our knowledge of genetic and molecular mechanisms controlling digestive efficiency, improve our understanding of how diet and pharmacological interventions influence body weight regulation, and open up new avenues of investigation. The inability to measure digestive efficiency means that our data interpretations may currently be flawed and we are missing opportunities to uncover novel molecular mechanisms related to body weight regulation. It is anticipated that acquiring a modern calorimeter will enhance the direct training of ~50 highly qualified personnel (HQP) per year across 6 NSERC-funded laboratories. Overall, we anticipate that acquiring a calorimeter will have immediate and significant benefits on numerous NSERC-funded research programs, and will directly enhance HQP productivity and training.