Exercise Modifies Inflammatory Responses by Changing the Epigenetic Landscape

Physical inactivity and low-grade systemic inflammation are associated with chronic metabolic diseases such as atherosclerosis, insulin resistance, obesity etc. It is of great value to study the exercise mediated benefits to alleviate inflammation. Preliminary work in our lab demonstrated that exercise with a particular intensity and duration led to reduced inflammatory responses in bone marrow derived macrophages (BMDMs) by inducing persistent metabolic changes in these cells. In this thesis, we explored how exercise is causing these long-lasting changes in inflammatory responses and hypothesized that it does so by inducing changes in chromatin accessibility leading to changes in gene expression. We employed an unbiased ATAC-seq (Assay for Transposase Accessible Chromatin- sequencing) analysis in BMDMs prepared from sedentary and exercised C57BL/6N mice and obtained a list of differentially accessible chromatin regions. We also demonstrated using real-time PCR that exercise-mediated changes in chromatin accessibility cause a reduction in gene expression of inflammatory genes. Our findings suggested that exercise is protective against inflammatory responses by causing persistent changes at chromatin level.