Excellence in Research - Investigating Smooth Muscle-based Regulation of Non-shivering Thermogenesis

本项目验证了小鼠在冷适应过程中平滑肌对产热有重要贡献的假设，并探讨了这些细胞产热的机制。哺乳动物和鸟类通过刺激特定细胞中的生化过程来增加体内的产热，从而适应寒冷的环境，从而在寒冷的温度下生存。迄今为止，已知的为调节体温而产生热量的特定细胞是那些由棕色脂肪和骨骼肌组成的细胞。这项研究将研究平滑肌细胞在低温环境中产生热量以保持动物体温的潜力，这种潜力以前未被认识到。这项研究将使用一种独特的动物模型，在这种模型中，从平滑肌细胞中去除一种刺激生化过程、增强产热的蛋白质。从这些研究中获得的知识可能对适当的细胞功能和体重维持具有重要意义。严格的学术和公民培训机会将提供给在STEM劳动力中寻求职业的少数族裔研究生。将开发一门结合教学和实践培训的新课程，以扩大代表性不足的学生在温度调节方面的知识。此外，该项目将吸引K-12公立学校的学生和外行社区，揭开科学研究过程的神秘面纱，让外行少数民族社区接触科学。该项目将建立哺乳动物体温调节和能量消耗的新范式，并扩大代表性不足的研究生参与stem相关基础研究。该项目验证了平滑肌调节能量消耗并通过基于血清和糖皮质激素诱导激酶1 （SGK1）的非寒颤产热（NST）机制促进温度稳态的假设。NST是体内热量的产生，对维持核心体温和能量消耗至关重要。实验将检查平滑肌和SGK1在平滑肌细胞（SMC）特异性SGK1缺失小鼠在热中性居住温度和冷挑战条件下的温度调节和能量消耗中的贡献和功能。初步研究表明，线粒体介导的产热过程在smc特异性SGK1缺失小鼠中得到增强。该项目将通过揭示SGK1在平滑肌中以前未知的产热作用，为NST建立一个新的范例。这项研究将有助于拓宽关于吸热动物如何保持体温并确保生存的科学知识，并可能导致未来减少人类肥胖的应用。此外，该提案将为莫尔豪斯医学院（Morehouse School of Medicine）就读研究生课程的少数族裔学生提供培训机会。该奖项将为学生提供机会进行研究，为科学文献做出贡献，并接受科学，学术和公民指导，以支持stem相关职业的未来就业，并为美国科学劳动力的多样化做出贡献。将纳入涉及非专业少数民族成员的社区项目，以加强他们对科学进程的了解。这个奖项是由历史上的黑人学院和大学联合资助的——综合活动办公室的卓越研究项目和生物科学理事会综合有机体系统部门的生理机制和生物力学项目。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project tests the hypothesis that smooth muscle contributes significantly to heat production during cold acclimation in mice, and investigates the mechanisms of heat production in these cells. Mammals and birds adjust to a cold environment by stimulating biochemical processes in specific cells to increase heat production within the body, allowing survival at cold temperatures. To date, the specific cells known to produce heat for body temperature regulation are those that comprise brown fat and skeletal muscle. This research will examine a previously unrecognized potential for smooth muscle cells to produce heat to keep animals warm when housed at a cold temperature. The study will use a unique animal model in which a protein that stimulates biochemical processes that enhance heat production is removed from smooth muscle cells. The knowledge gained from these studies may have important implications for proper cell function and body weight maintenance. Rigorous academic and civic training opportunities will be provided to under-represented minority graduate students pursuing careers in the STEM workforce. A new course that incorporates didactic and hands-on training will be developed to expand the knowledge of under-represented students in temperature regulation. Additionally, this project will engage K-12 public school students and the lay community to demystify the scientific research process and expose the lay minority community to science. This project will establish a novel paradigm for thermoregulation and energy expenditure in mammals and broaden the participation of under-represented graduate students in STEM-related basic research. The project tests the hypothesis that smooth muscle regulates energy expenditure and contributes to temperature homeostasis through a serum and glucocorticoid-inducible kinase 1 (SGK1)-based mechanism of non-shivering thermogenesis (NST). NST is the production of internal body heat and is crucial for maintenance of core body temperature and energy expenditure. Experiments will examine the contribution and function of smooth muscle and SGK1 in thermoregulation and energy expenditure in smooth-muscle-cell (SMC)-specific SGK1 null mice under thermoneutral housing temperatures and cold-challenged conditions. Preliminary studies demonstrate that thermogenic processes mediated by the mitochondria are enhanced in SMC-specific SGK1 null mice. This project will establish a novel paradigm for NST by uncovering a previously unknown thermogenic role for SGK1 in smooth muscle. The research will help to broaden scientific knowledge of how endothermic animals are able to maintain body temperature and ensure survival, and could lead to future applications for reducing obesity in humans. In addition, this proposal will facilitate training opportunities for under-represented minority students who are enrolled in the graduate programs at Morehouse School of Medicine. This award will provide an opportunity for students to conduct research, contribute to the body of scientific literature, and receive scientific, academic and civic mentorship to support future employment in STEM-related careers and contribute to the diversification of the American scientific workforce. Community-based projects involving lay minority members will be incorporated to enhance their exposure to the scientific process.This award is co-funded by the Historically Black Colleges and Universities - Excellence in Research Program in the Office of Integrative Activities and the Physiological Mechanisms and Biomechanics Program in the Division of Integrative Organismal Systems, Directorate for Biological Sciences.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.