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: 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=659875
• 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，通过其多种代谢物和脂肪因子（脂肪组织分泌的细胞信号蛋白）深刻地影响着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，在维持全身能量和代谢稳态中起着关键作用，性类固醇激素在脂肪组织生物学和能量稳态中都起着重要作用。此外，已知性别差异存在于脂肪组织在体内能量和代谢稳态中的作用。然而，介导脂肪组织功能差异并进而影响机体代谢稳态的各种因素尚未得到很好的探讨。破译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。在我之前的发现基金下，我的团队发现了一种蛋白质，禁止蛋白，在脂肪细胞形成中起着重要作用。为了进一步探索禁止素在全身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生产禁止素，开发了一种新型转基因小鼠。禁止素转基因小鼠的脂肪组织质量以性别中立的方式增加，但它们在身体代谢特性上表现出性别差异。我们的数据表明，禁止素在维持脂肪组织稳态方面发挥着重要作用，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禁止素在脂肪细胞生物学中的作用。在这项研究中，我的HQP和我将探索性类固醇激素和禁止素之间相互作用的机制，导致脂肪组织功能和代谢稳态在全身水平上的性别差异。这项拟议的研究将为禁止素在脂肪细胞生物学中作用的潜在机制提供新的见解，包括其对脂肪细胞功能影响的性别差异。这些信息对于我们进一步了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，这是哺乳动物全身生理学的一个基本方面。我预计这个周期至少会有8-10名HQP在我的项目中接受培训。