NSF Award
2425583
Despite the importance of metabolism on whole body homeostasis, little is known about how adipose tissue, the major regulator of metabolism, functions in different environments, including in space, where mechanical forces are experienced differently, and radiation is stronger than on earth, leading to accelerated aging. Here, we plan to explore how true microgravity and radiation lead to altered cellular organization and thus metabolic (dys)function. This will be achieved by sending engineered adipose tissue aboard the International Space Station (ISS) for six months. Changes to cell and tissue remodeling and overall tissue function, looking specifically at adipocyte function and inflammatory/aging responses will be characterized upon return to earth. The broader impacts of this research include new targets for metabolic health in normal and aged populations. The US aging population is rapidly growing, where the 2020 Census found 1 in 6 people are 65 or older, which is nearly a 40 percent increase in 10 years (Census.gov statistics). A healthy metabolism is associated with longevity. However, 42 percent of US adults are classified as obese (CDC.gov statistics), where impaired quality of life, increased risk of many co-morbidities (cardiovascular disease, musculoskeletal disease, cancer, stroke, etc), decreased work productivity and increased healthcare costs become a growing problem. Therefore, development of models of adipose tissue function and aging are urgently needed to ensure not only a healthy and good quality of life, but also to ensure the workforce is strong and healthcare costs are limited. <br/><br/>Adipocytes in engineered adipose tissue respond to simulated microgravity by remodeling their cortical actin, which improved insulin mediated glucose uptake and lipid metabolism. However, simulated gravity differs from true microgravity in shear fluid stresses and radiation. It is hypothesized that exposure to true microgravity would demonstrate differential responses in cellular mechanosensors by increased radiation and altered fluid shear stresses, thus changing the cytoskeletal response and ultimately the overall tissue response when compared to simulated microgravity. These hypotheses will be tested by comparing engineered adipose tissue constructs maintained on the ISS versus ground based simulated microgravity and static controls, to evaluate changes to adipocyte function (e.g. glucose uptake, lipid metabolism, adipokine release, key adipocyte gene/protein expression) and mechanosensitive pathways/receptors (e.g. actin, RhoA, Piezo1, TRPV) and overall tissue organization via extracellular matrix remodeling. Successful completion of the proposed work, would establish how true microgravity affects engineered adipose tissue function via mechano-signaling, potentially identifying new mechanosensitive targets for metabolic (dys)function on earth as a model of accelerated aging, and for metabolic (dys)function for those traveling in space. This would be the first time human adipose tissue models will be sent to ISS and would provide invaluable insight to this tissue function. The broader impacts of this work would have implications for society, national security, workforce, and economy.<br/><br/>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.
