Regulation of whole-body energy homeostasis

全身能量稳态的调节

• 批准号: RGPIN-2016-05358
• 负责人: Ceddia, Rolando
• 金额: $ 2.55万
• 依托单位: York University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=647003
• 关键词: Regulation; whole; body; energy; homeostasis

This ongoing research program is designed to develop a greater understanding of the basic fundamental physiological and molecular mechanisms involved in the regulation of substrate partitioning and energy balance at the cell, tissue, and whole-body levels. It includes in vivo and in vitro experimental approaches designed to elucidate how endocrine, molecular, and physiological mechanisms that affect energy storage and dissipation in major organs that regulate whole-body energy homeostasis. It focuses on understanding the energy-sparing and energy-dissipating mechanisms that are activated under conditions of altered food intake (energy deficit and surplus) and increased energy expenditure (chronic endurance exercise). 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, and hormonal secretions. Furthermore, this research program will advance our understanding of the mechanisms that regulate adiposity and its potential association with the development of metabolic disorders such as obesity and type 2 diabetes. For in vivo studies, rodents are exposed to caloric restriction, caloric surplus (high-fat diet), exercise-mediated increased energy expenditure (treadmill endurance training), as well as to acute and chronic treatment with pharmacological agents that affect cellular and whole-body substrate partitioning. Indirect calorimetry is used to assess 24-h whole-body energy expenditure, metabolic partitioning, and alterations in resting metabolic rate. Time-course analysis of body composition (lean body mass and fat mass) are performed using the microCT system that performs imaging similar to CT scans for humans, but is designed specifically for mice and rats. For in vitro studies, 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 Oxygraph-2k instrument), and for the analysis of gene expression (mRNA expression by Real-time PCR) and signaling 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.

这项正在进行的研究计划旨在更好地了解细胞，组织和全身水平上基质分配和能量平衡调节所涉及的基本生理和分子机制。它包括体内和体外实验方法，旨在阐明内分泌，分子和生理机制如何影响调节全身能量稳态的主要器官的能量储存和耗散。它侧重于了解在改变食物摄入（能量不足和过剩）和增加能量消耗（慢性耐力运动）的条件下激活的能量节省和能量耗散机制。这一点很重要，因为储存和保存能量的能力对生存和生殖能力至关重要，并且受到饮食，运动和激素分泌的影响。此外，这项研究计划将促进我们对调节肥胖的机制及其与代谢紊乱（如肥胖和2型糖尿病）发展的潜在关联的理解。对于体内研究，啮齿动物暴露于热量限制、热量过剩（高脂饮食）、运动介导的能量消耗增加（跑步机耐力训练）以及影响细胞和全身底物分配的药物的急性和慢性治疗。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。使用microCT系统进行身体成分（瘦体重和脂肪量）的时间过程分析，该系统执行与人类CT扫描类似的成像，但专为小鼠和大鼠设计。对于体外研究，将来自暴露于上述各种条件的啮齿动物的分离的细胞和组织用于孵育，并使用放射性标记的示踪剂测定葡萄糖和脂质代谢，以评估氧消耗（通过使用Oroboros Oxygraph-2k仪器），以及基因表达的分析（mRNA表达，通过实时PCR）和信号传导机制（蛋白质印迹法测定的特定蛋白质的含量和磷酸化）参与控制细胞，组织，和全身能量代谢。