Immune cell phenotype and function : impact of type 2 diabetes, obesity, and exercise

Chronic low-grade inflammation plays a key role in obesity and type 2 diabetes (T2D). Research on inflammation in obesity and T2D has tended to focus on inhibiting pro-inflammatory signaling with the function of anti-inflammatory cytokines being largely unexplored. Exercise is a cornerstone in the treatment of obesity and T2D and may confer some of its beneficial effects through anti-inflammatory mechanisms; however, the optimal anti-inflammatory exercise modality remains unclear. High-intensity interval training (HIIT) has become popular as a time efficient alternative to moderate intensity continuous training (MICT) but whether HIIT is anti-inflammatory like MICT, or pro-inflammatory, is unclear. This thesis examined the impact of T2D, obesity, and exercise on immune cell phenotype and function. In the first study, it was found that interleukin (IL) 10 was less effective at inhibiting inflammation in immune cells from individuals with T2D, indicating that “IL10 resistance” may impact chronic inflammation in T2D. The impact of exercise on immune cell phenotype and function were then examined in inactive adults with obesity who were randomized to short-term HIIT or MICT. HIIT and MICT reduced the ability of IL10 to inhibit inflammation in blood leukocytes, with a greater effect seen after HIIT. There were differential effects of HIIT and MICT on the anti-inflammatory functioning of IL6. During obesity and T2D, there is increased leukocyte migration/infiltration into adipose through a process mediated by chemokines and their respective chemokine receptors. HIIT and MICT resulted in differential effects on leukocyte chemokine receptors. MICT downregulated monocyte chemokine receptors, CCR2 and CXCR2, whereas HIIT upregulated monocyte, neutrophil and T cell chemokine receptor, CCR5. Exercise-induced changes in IL10 function and leukocyte chemokine receptors occurred in the absence of weight/fat loss, suggesting that these were direct immunomodulatory effects of exercise. All effects of exercise on immune cell phenotype and function occurred without changes in plasma cytokines or chemokines. As levels of circulating cytokines/chemokines are often used to determine whether a treatment is pro- or anti-inflammatory the collective findings of these studies indicate that important immunomodulatory impacts of T2D and different types of exercise could be missed unless immune cell phenotype and function are also assessed.Graduate Studies, College of (Okanagan)Graduat