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199160 https://hdl.handle.net/2286/R.2.N.199160 http://rightsstatements.org/vocab/InC/1.0/ All Rights Reserved 2024 130 pages Doctoral Dissertation Academic theses Text eng Serrano, Nathan Katsanos, Christos S Dickinson, Jared M Rawls, Alan Hyatt, Jon-Philippe K Arizona State University Partial requirement for: Ph.D., Arizona State University, 2024 Field of study: Biology Skeletal muscle is a metabolic sink crucial for maintaining whole-body homeostasis. It disposes of glucose and lipids (e.g., free fatty acids), which contribute to obesity and metabolic diseases like Type 2 Diabetes and insulin resistance. This dissertation will discuss how muscle fibers are characterized by myosin heavy chain (MHC) isoforms, dictating skeletal muscle fiber types (FT) linked to metabolic properties. Type I (MHC I) muscle fibers are associated with greater glucose and lipid uptake and utilization, abundant mitochondria, and capillaries, resulting in higher fatigue resistance. Type II muscle fibers, further classified as Type IIa (MHC IIa) and Type IIx (MHC IIx), have reduced glucose and lipid metabolism due to fewer transport proteins (insulin receptors and GLUT4 transporters) and lower mitochondrial content. Assessing muscle FTs is best done by evaluating individual muscle fibers for accurate characterization of muscle fiber phenotypes as discussed in chapter 2. The final chapter discusses the importance of female FT proportions as a potential contributor to overall body mass and insulin sensitivity. Our findings show that females with obesity express lower proportions of Type I muscle fibers and a higher proportion of fibers co-expressing multiple MHC isoforms (e.g., Type I/IIa, IIa/IIx, I/IIa/IIx, and I/IIx). Specifically, MHC IIx expressing fiber types indicated by the average expression of MHC IIx isoforms within the Type IIa/IIx hybrids greater in females with obesity versus those without obesity. Furthermore, the mRNA expression of Myh (e.g., Myh 7, 2, and 1), which codes for MHC I, IIa, and IIx respectively, was 27-fold greater for Myh 1 in females with obesity. MicroRNAs (miRNAs) mediate mRNA expression and post-transcriptionally silence protein synthesis. Specifically, miR 208b-3p and miR 499a-5p are suggested contributors to FT expression; however, data in the current study were inconclusive. FT proportions and the mechanisms mediating their expression in females with obesity are potential contributors to associated metabolic status. Future research should further evaluate protein-protein and mRNA-protein interactions that may moderate muscle FT expression. Biology Physiology expression Genetics Metabolism Skeletal Muscle Skeletal Muscle Fiber Phenotypes in Obesity: Implications and Fiber Type Expression within Females Specifically