Regulation of whole-body energy homeostasis

全身能量稳态的调节

• 批准号: RGPIN-2022-04517
• 负责人: Ceddia, Rolando
• 金额: $ 2.04万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757797
• 关键词: Regulation; whole; body; energy; homeostasis

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.

该研究计划的重点是发展在细胞，组织和全身水平的葡萄糖和脂肪代谢和能量平衡的调节所涉及的基本生理和分子机制的更好的理解。它包括使用活生物体（大鼠和小鼠）和分离的细胞和组织的实验，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。它侧重于了解在热应激（冷），慢性耐力运动和操纵饮食组成的条件下改变肥胖（脂肪的增加和减少）的条件下激活的能量节省和能量消耗机制。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，环境变化和激素分泌的影响。此外，这项研究计划将促进我们对调节骨骼肌、肝脏、白色和棕色脂肪组织中肥胖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）将暴露于以下干预措施：1）富含高脂肪蔗糖的饮食以促进脂肪组织生长，2）使用跑步机跑步的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产热并诱导白色脂肪组织布朗宁，和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。使用动物解剖技术和/或microCT系统进行身体组成（瘦体重和肥胖）的时间过程分析，该系统执行与人类CT扫描类似的成像，但它是专门为小鼠和大鼠设计的。此外，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，实时PCR）和信号传导机制蛋白质组学研究表明，蛋白质组学研究表明，蛋白质组学研究这项研究很重要，因为它将扩大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，这项研究将促进加拿大的基础转化科学，提高加拿大科学家的素质和竞争力。