Medicine and Health Sciences Commons^™

Tumor-Derived Proteins And Mitochondrial Dysfunction In Lung Cancer-Induced Cachexia, Julie B. Mclean

Theses and Dissertations--Physiology

Lung tumors secrete multiple factors that contribute to cachexia, a severe wasting syndrome that includes loss of muscle mass, weakness, and fatigue. 80% of advanced lung cancer patients experience cachexia, which cannot be reversed by nutritional interventions, diminishes response to and tolerance of cancer treatments, and increases morbidity and mortality. Despite a multitude of clinical trials, there are currently no approved treatments. This deficiency suggests that not all of the factors that contribute to cachexia have been identified.

Cancer is frequently accompanied by an increase in cyclooxygenase-2 (COX-2), a hallmark of inflammation. Clinical trials for COX-2 inhibitors have resulted in …

Global-Scale Analysis Of The Dynamic Transcriptional Adaptations Within Skeletal Muscle During Hypertrophic Growth, Tyler Kirby

Theses and Dissertations--Physiology

Skeletal muscle possesses remarkable plasticity in responses to altered mechanical load. An established murine model used to increase mechanical load on a muscle is the surgical removal of the gastrocnemius and soleus muscles, thereby placing a functional overload on the plantaris muscle. As a consequence, there is hypertrophic growth of the plantaris muscle. We used this model to study the molecular mechanisms regulating skeletal muscle hypertrophy.

Aged skeletal muscle demonstrates blunted hypertrophic growth in response to functional overload. We hypothesized that an alteration in gene expression would contribute to the blunted hypertrophic response observed with aging. However, the difference in …

Impaired Glucose Metabolism In The Absence Of Skeletal Muscle Brain And Muscle Arnt-Like-Protein 1 (Bmal1), Brianna D. Harfmann

Theses and Dissertations--Physiology

Metabolism is a critical physiological function that works to generate energy for cells, store substrates and maintain homoeostasis. Alterations in normal metabolism can have a severe effect on physiology, leading to metabolic disease. Skeletal muscle is a key metabolic tissue, taking up ~80% of postprandial glucose. Therefore it contributes considerably to glucose metabolism: glucose uptake, oxidation and homeostasis. To address the role of the skeletal muscle clock in insulin sensitivity and glucose tolerance, our lab generated an inducible skeletal muscle specific Bmal1^-/- mouse (iMSBmal1^-/-). 5 weeks post-recombination we observed impairment in both insulin- and AICAR-stimulated skeletal …