Regulation of whole-body energy homeostasis

该研究项目的重点是更好地了解细胞、组织和全身水平上葡萄糖和脂肪代谢以及能量平衡调节所涉及的基本生理和分子机制。它包括使用活体（大鼠和小鼠）以及分离的细胞和组织进行的实验，旨在阐明内分泌、分子和生理机制如何影响调节全身能量代谢的主要器官的能量储存和消耗。它的重点是了解在热应激（冷）、长期耐力运动和饮食成分控制的条件下肥胖改变（脂肪增加和减少）的情况下激活的能量节约和能量消耗机制。这很重要，因为储存和保存能量的能力对于生存和生殖能力至关重要，并且受到饮食、锻炼、环境变化和荷尔蒙分泌的影响。此外，该研究计划将增进我们对调节骨骼肌、肝脏以及白色和棕色脂肪组织中的脂肪和底物分配的分子和生理机制的理解。雄性和雌性啮齿动物（大鼠和转基因小鼠）将接受以下干预措施：1）富含蔗糖的高脂饮食，以促进脂肪组织生长，2）使用跑步机跑步进行耐力训练，以增加能量消耗并减少肥胖，3）冷驯化以激活棕色脂肪生热作用并诱导白色脂肪组织褐变，4）生酮饮食以改变细胞和全身底物分配。间接量热法用于评估 24 小时全身能量消耗、代谢分配和静息代谢率的变化。身体成分（瘦体重和肥胖）的时程分析是使用动物解剖技术和/或 microCT 系统进行的，该系统执行类似于人类 CT 扫描的成像，但它是专门为小鼠和大鼠设计的。此外，从暴露于上述各种条件的啮齿动物中分离的细胞和组织可用于孵育和使用放射性标记示踪剂测定葡萄糖和脂质代谢，用于评估耗氧量（通过使用 Oroboros Oxygraph2k 仪器），以及用于分析基因表达（通过实时 PCR 进行 mRNA 表达）和信号机制（通过蛋白质印迹分析特定蛋白质的含量和磷酸化），这些机制涉及控制细胞、组织和全身能量代谢的途径的调节。这项研究很重要，因为它将扩展我们在脂肪组织生物学、体重调节、营养和运动生理学领域的知识，并为学生的专业培训提供机会。因此，这项研究将推动加拿大基础转化科学的发展，并提高加拿大科学家的资质和竞争力。

This research program focuses on developing a greater understanding of the basic fundamental physiological and molecular mechanisms involved in the regulation of glucose and fat metabolism and energy balance at the cell, tissue, and whole-body levels. It includes experiments using living organisms (rats and mice) and isolated cells and tissues designed to elucidate how endocrine, molecular, and physiological mechanisms affect energy storage and consumption in major organs that regulate whole-body energy metabolism. It focuses on understanding the energy-sparing and energy-consuming mechanisms that are activated under conditions of altered adiposity (gain and loss of fat) under conditions of thermic stress (cold), chronic endurance exercise, and manipulation of dietary composition. This is important because the ability to store and conserve energy is essential for survival and reproductive capacity, and it is affected by diet, exercise, environmental changes, and hormonal secretions. Furthermore, this research program will advance our understanding of the molecular and physiological mechanisms that regulate adiposity and substrate partitioning in skeletal muscle, liver, and white and brown adipose tissues. Male and female rodents (rats and genetically modified mice) will be exposed to the following interventions: 1) a high-fat sucrose-enriched diet to promote adipose tissue growth, 2) endurance training using treadmill running to increased energy expenditure and reduce adiposity, 3) cold acclimation to activate brown fat thermogenesis and induce white adipose tissue browning, and 4) a ketogenic diet to alter cellular and whole-body substrate partitioning. Indirect calorimetry is used to assess 24h whole-body energy expenditure, metabolic partitioning, and alterations in resting metabolic rate. Time course analysis of body composition (lean mass and adiposity) are performed using animal dissection techniques and/or the microCT system that performs imaging similar to CT scans for humans, but it is designed specifically for mice and rats. Also, isolated cells and tissues from rodents exposed to the various conditions described above are used for incubation and determination of glucose and lipid metabolism using radiolabeled tracers, for assessment of oxygen consumption (by using the Oroboros Oxygraph2k instrument), and for the analysis of gene expression (mRNA expression by Realtime PCR) and signalling mechanisms (content and phosphorylation of specific proteins by Western blot) involved in the regulation of pathways that control cell, tissue, and whole-body energy metabolism. This research is important as it will expand our knowledge in fields of adipose tissue biology, body weight regulation, nutrition, and exercise physiology and provide opportunities for specialized training of students. Thus, this research will advance basic translational science in Canada and increase the qualification and competitiveness of Canadian scientists.