Date of Graduation

12-2025

Document Type

Thesis

Degree Name

Master of Science in Exercise Science (MS)

Degree Level

Graduate

Department

Health, Human Performance and Recreation

Advisor/Mentor

Rosa-Caldwell, Megan

Committee Member

Murach, Kevin

Second Committee Member

Washington, Tyrone

Keywords

Anorexia Nervosa; ECM; Genes; RNA-Sequencing; Skeletal Muscle; Transcriptomics

Abstract

BACKGROUND: Anorexia Nervosa (AN) is a psychiatric disorder marked by severe chronic caloric restriction and is primarily diagnosed through psychological and behavioral symptoms. AN has the highest mortality of any psychiatric disorder with an increased risk of all-cause mortality. Many individuals with a history of AN experience incomplete recovery despite intervention treatment. Skeletal muscle molecular mechanisms under chronic energy deprivation remain poorly understood. PURPOSE: To investigate transcriptomic profiles of the gastrocnemius muscle following one month of a rodent model of AN. This study analyzed whether the molecular changes correlate with collected muscular force data to provide a comprehensive understanding of the mechanisms under simulated AN. METHODS: 18 Sprague Dawley rats were divided into two groups: a control group (CON)(n = 9) and an AN group (AN) (n = 9) that were subjected to a 30-day caloric restriction. AN rats were provided with ~50%–60% less food than baseline consumption. CON rats were allowed ad libitum access all throughout the intervention. Muscle performance was quantified using grip strength and footplate electrical stimulation. After 30 days, gastrocnemius muscles were harvested and used for RNA-sequencing. RESULTS: AN exhibited significant reduction in body weight, gastrocnemius mass, grip strength, and area under the curve for maximal tetanus. Footplate measurements also showed an increased time-to-peak in AN with no differences in peak force production (p>0.05). Transcriptomic analysis identified 986 differentials expressed genes (FDR < 0.05). Applying an additional biological cutoff (|fold change| ≥1.5) yielded 344 genes with substantial expression changes. Downregulated genes included those associated with calcium handling, extracellular matrix, and circadian regulation. Upregulated genes included atrophy-associated genes and oxidative stress response genes. Higher muscle performance correlated with expression of glycolytic, Ca²⁺-handling, and ECM collagen genes, while the atrophy markers related inversely to force output. Faster time-to-peak and greater peak force associated with fast-fiber/contractile genes and collagen VI/III. CONCLUSION: Food restriction induced a global change in transcriptomic alterations governed by ECM integrity, metabolic stress and calcium-handling. Muscle performance correlation indicated that preserving ECM organization and excitation-contraction coupling enhances better mechanics under caloric restriction. These findings provide a molecular framework for understanding muscle dysfunction in AN and highlight potential targets for therapeutic intervention.

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