The role of prohibitin in adipocyte biology

抑制素在脂肪细胞生物学中的作用

• 批准号: RGPIN-2016-06013
• 负责人: Mishra, Suresh
• 金额: $ 2.26万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=616049
• 关键词: role; prohibitin; adipocyte; biology

Adipose tissue is a complex, multicellular structure that profoundly influences the function of nearly all other organ systems in the body through its diverse metabolite and adipokine (cell signaling proteins secreted by adipose tissue). Adipocytes, the structural and functional unit of adipose tissue plays a key role in maintaining whole body energy homeostasis. To perform this specialized function, adipocytes rely on their mitochondria, the powerhouse of the cell. Recent evidence suggests that mitochondrial biogenesis (production of new mitochondria) is integral to adipocyte formation. However, various proteins involved in mitochondrial biogenesis during adipocyte formation are not explored. In addition, despite a critical role of mitochondria in adipocyte biology, the role of adipocyte mitochondria in adipose tissue homeostasis and on adipokine secretion are not well understood. Deciphering adipocyte biology is an important component of understanding the role of adipose tissue in energy homeostasis and metabolic regulation in the body. Under my previous Discovery Grant, my team discovered that a protein, prohibitin, has an important role in adipocyte formation. To further explore the role of prohibitin in adipose tissue biology at the whole body level, my team developed a novel transgenic mouse by over-producing prohibitin in adipocytes. Prohibitin transgenic mice displayed an increase in adipocyte mitochondrial biogenesis and adipose tissue mass in a sex-neutral manner, but sex differences in their body’s metabolic and physiological properties. Our data suggests that prohibitin has an important role in the maintenance of adipose tissue homeostasis and point towards sex differences in its effect on adipocytes function. However, the underlying mechanisms involved remain to be determined. Clearly, further investigation is required to determine the role prohibitin in adipocyte biology. In this study, my HQP and I will explore how increased level of a single protein (prohibitin) leads to a process (mitochondrial biogenesis) that requires coordination of hundred of proteins, and why their functional consequences are different in males and females. The proposed research will provide novel insights in the underlying mechanisms involved in the role of prohibitin in adipocytes biology including sex differences in its effect on adipocytes function. Such information is critical to advance our understanding of the role of adipose tissue in the maintenance of energy homeostasis and metabolic regulation in the body. I anticipate that at least 8 HQP will be trained in my program this cycle.

脂肪组织是一种复杂的多细胞结构，通过其多样化的代谢物和脂肪因子（脂肪组织分泌的细胞信号蛋白）深刻影响体内几乎所有其他器官系统的功能。脂肪细胞是脂肪组织的结构和功能单位，在维持全身能量平衡中起着关键作用。为了执行这一专门功能，脂肪细胞依赖于它们的线粒体，细胞的动力。最近的证据表明，线粒体生物合成（新线粒体的产生）是脂肪细胞形成的组成部分。然而，在脂肪细胞形成过程中参与线粒体生物合成的各种蛋白质尚未探索。此外，尽管线粒体在脂肪细胞生物学中起关键作用，但脂肪细胞线粒体在脂肪组织稳态和脂肪因子分泌中的作用还不清楚。解读脂肪细胞生物学是理解脂肪组织在体内能量稳态和代谢调节中的作用的重要组成部分。在我之前的发现资助下，我的团队发现了一种蛋白质，抑制素，在脂肪细胞形成中起着重要作用。为了进一步探索Prohibitin在全身水平脂肪组织生物学中的作用，我的团队通过在脂肪细胞中过量产生Prohibitin开发了一种新型转基因小鼠。Prohibitin转基因小鼠表现出脂肪细胞线粒体生物合成和脂肪组织质量的增加，但在其身体的代谢和生理特性的性别差异。我们的数据表明，prohibitin在维持脂肪组织稳态中具有重要作用，并指出其对脂肪细胞功能的影响存在性别差异。然而，所涉及的基本机制仍有待确定。显然，需要进一步的研究来确定抑制素在脂肪细胞生物学中的作用。在这项研究中，我和我的HQP将探索单一蛋白质（抑制素）水平的增加如何导致需要数百种蛋白质协调的过程（线粒体生物合成），以及为什么它们的功能后果在男性和女性中不同。这项研究将为抑制素在脂肪细胞生物学中的作用提供新的见解，包括其对脂肪细胞功能影响的性别差异。这些信息对于促进我们理解脂肪组织在维持体内能量稳态和代谢调节中的作用至关重要。我预计至少有8名HQP将在我的项目中接受培训。