Date of Award
Spring 2019
Project
Capstone - Open Access
Concentration
Exercise and Sport Science
Degree Name
Master of Science (MS)
Abstract
Introduction: Chronic sterile inflammation that underlies obesity can promote unhealthy cellular changes eventually leading to a decline in metabolic health and type-2 diabetes. Dysregulation of cellular processes during the initiation and progression of obesity can impair inflammatory homeostasis leading to a proinflammatory Th17 cytokine profile by CD4 + Tcells. Our ongoing research efforts are to understand the mechanistic link between the changes in a cellular housekeeping process known as autophagy and the regulation of Th17 cytokines in obese non diabetic and diabetic subjects. Methods: We assessed cellular protein expression and colocalization using immunoblotting, immunofluorescence, flow cytometry and ELISA assays. Results: We observed that diabetic obese subjects had lower autophagy (p<0.05), mitochondrial fission (p<0.05) and lower expression of antioxidant proteins such as nicotinamide transhydrogenase and super oxide dismutase 2(numerical reduction). The diabetic subjects had numerically higher mitochondrial fusion protein expression, significantly higher mitochondrial mass and mitochondrial colocalization with lysosomal protein LAMP1(p<0.05). No difference was observed in cytokines IL17A and IL-17F between the groups as assessed via intracellular staining. Conclusion: The preliminary data presented in this study shows that CD4 + T cells from obese diabetic subjects have significantly higher number of fused mitochondria along with lower mitochondrial antioxidant protein expression. While we observed that the cellular recycling process of autophagy is lower in the diabetic subjects the mitochondrial colocalization with lysosomal protein appears to be intact. Further experimental analysis is required to understand this discrepancy.
Recommended Citation
Keady, Alanna, "Changes in Mitochondrial Protein Expression in Human CD4 + T cells During the Initiation and Progression of Diabetes" (2019). Health Sciences Student Work. 20.
https://scholarworks.merrimack.edu/hsc_studentpub/20