CAREER: Purposeful Tissue-Engineered Skeletal Muscle: Advancing Research and Education

University Of Texas At San Antonio, San Antonio TX

Investigators

Abstract

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2). The skeletal muscles of patients with diseases like Type 2 diabetes are characterized by an increase in the abundance of fat cells, known as adipocytes. White, brown, and beige adipocytes can exist within tissues, with each type influencing tissue function in distinct ways. The research completed with this Faculty Early Career Development Program (CAREER) project will advance the understanding of the different types of adipocytes in diabetic skeletal muscle, and during muscle repair and regeneration. A tissue-engineered model of skeletal muscle will be used to explore the role of adipocytes in skeletal muscle using conditions that mimic diabetes and muscle injury. Research objectives will be integrated with education and outreach to broadly impact STEM students, with more targeted directives to influence Veterans and underrepresented minorities. The overall goal of this CAREER project is to develop a comprehensive understanding of adipocyte-dependent effects in skeletal muscle during the progression of Type 2 diabetes and during repair and regeneration after injury. The goal of the first objective is to determine the effects of Type 2 diabetes, adipocyte type, and adipocyte differentiation capacity on skeletal muscle properties. The tissue-engineered skeletal muscle model will be used to examine how adipocyte type and diabetes influence metabolism; the ability to change adipocyte phenotype (inducing a white to brown or beige transition) within muscle, and the role of sirtuin-1 (SIRT1) in mediating these changes. The goal of the second objective is to elucidate the role of skeletal muscle adipocytes in skeletal muscle regeneration. The role of adipocyte type in recovery of functional outcomes in skeletal muscle will be interrogated. The use of injury will identify conditions in which adipocyte-dependent effects may be altered. The use of an engineered model where both injury and Type 2 diabetes are implemented provides an opportunity to better understand these facets as they relate to adipocytes in diabetic skeletal muscle. This knowledge will lead to new avenues for investigation, supporting the development of platforms to develop personalized approaches for targeting skeletal muscle complications. 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.