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

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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.