Illuminating the relationship between prohibitin and sex steroid hormones in adipocyte biology

阐明脂肪细胞生物学中抑制素和性类固醇激素之间的关系

• 批准号: RGPIN-2017-04962
• 负责人: Mishra, Suresh
• 金额: $ 2.04万
• 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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=711317
• 关键词: Illuminating; relationship; between; prohibitin; sex

Fat 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 fat tissue). Fat cell, the structural and functional unit of fat tissue plays a key role in maintaining whole body energy and metabolic homeostasis, and sex steroid hormones have a role in both fat tissue biology and in energy homeostasis. Furthermore, sex differences are known to exist in the role of fat tissue in energy and metabolic homeostasis in the body. However, various factors that mediate such differences in fat tissue functions and consequently on the body's metabolic homeostasis are not well explored. Deciphering sex differences in fat cell biology is an important component of understanding the role of fat 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 fat cell formation. To further explore the role of prohibitin in fat tissue biology at the whole body level, my team developed a novel transgenic mouse by over-producing prohibitin in fat cells. Prohibitin transgenic mice displayed an increase in fat tissue mass in a sex-neutral manner, but they showed sex differences in their body's metabolic properties. Our data suggests that prohibitin has an important role in the maintenance of fat tissue homeostasis and point towards sex differences in its effect on fat cell function. However, the underlying mechanisms involved remain to be determined. Clearly, further investigation is required to determine the role prohibitin in fat cell biology. In this study, my HQP and I will explore the mechanisms involved in the interplay between sex steroids hormones and prohibitin which leads to sex differences in fat tissue functions and metabolic homeostasis at the systemic level. The proposed research will provide novel insights into the underlying mechanisms involved in the role of prohibitin in fat cell biology including sex differences in its effect on fat cell function. Such information is crucial to advance our understanding of the role of fat tissue in the maintenance of energy homeostasis and metabolic regulation in the body in a sex-specific manner, which is a fundamental aspect of the whole body physiology in mammals. I anticipate that at least 8-10 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）深刻影响身体中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，在维持全身能量和代谢平衡中起着关键作用，性类固醇激素在脂肪组织生物学和能量平衡中起着重要作用。此外，已知脂肪组织在体内能量和代谢稳态中的作用存在性别差异。然而，各种因素，介导这种差异，脂肪组织的功能，因此对身体的代谢稳态没有很好地探讨。解读脂肪细胞生物学中的性别差异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在全身水平上在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转基因小鼠以性别中立的方式显示脂肪组织质量的增加，但它们在身体的代谢特性方面表现出性别差异。我们的数据表明，prohibitin在维持脂肪组织的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将探讨性类固醇激素和抑制素之间的相互作用，导致脂肪组织功能和代谢稳态在系统水平上的性别差异的机制。拟议的研究将提供新的见解的潜在机制参与的作用，抑制素在脂肪细胞生物学，包括性别差异，其影响脂肪细胞功能。这些信息是至关重要的，以促进我们的理解脂肪组织在维持能量稳态和代谢调节中的作用，在身体中的性别特异性的方式，这是一个基本方面的全身生理哺乳动物。我预计至少有8-10名HQP将在我的项目中接受培训。