Exercise decreases the number and modifies the transcriptome of M1 macrophages and CD8+ T cells in non-occluded epicardial adipose tissue of female pigs

Epicardial adipose tissue (EAT) regulates lipid metabolism and immune cell recruitment in coronary arteries. Increased EAT contributes to coronary artery disease (CAD), but exercise prevents CAD. We hypothesized that exercise, irrespective of CAD presence, would produce EAT with increased M2 macrophages and upregulation of anti-inflammatory cytokine transcripts. Female Yucatan pigs (<i>n</i> = 7) were sedentary or exercised, and the left circumflex coronary artery was occluded or remained nonoccluded (2 × 2 design). Bulk and single-nuclei transcriptomic sequencing performed on EAT identified immune, endothelial, smooth muscle, adipocytes, adipocyte progenitor cells (APSCs), and neuronal cells, with adipocytes and APSCs predominant. Nonoccluded (N) sedentary (Sed) EAT had the most M1 macrophages and CD8⁺ T cells. Sed EAT had the most cells expressing tumor necrosis factor (TNF) superfamily genes. Exercise (Ex) upregulated peroxisome proliferator-activated receptor (<i>PPAR</i>) γ (<i>G</i>) expression and enriched PPAR signaling, which suppresses activation, in macrophages and T cells, particularly in occluded (O) Ex EAT. By contrast, N_Ex EAT had few CD8⁺ T cells with low <i>PPARG</i> expression. Adipocytes and immune cells in O_Sed EAT had the most communication via growth factors and adhesion molecules. Exercise mitigates EAT inflammation via modulation of immune cell subpopulations, decreased TNF superfamily, and increased <i>PPARG</i> gene expression, and decreased communication between adipocytes and immune cells. However, the effect of exercise on the EAT immune environment is modulated by coronary artery occlusion status. Future studies of the impact of exercise and coronary artery occlusion on EAT would benefit from using a progressive nutritionally induced model of CAD.<b>NEW & NOTEWORTHY</b> A sedentary lifestyle increases the number of inflammatory M1 macrophages and CD8⁺ T cells, their expression of tumor necrosis factor genes, and the number of communications between these immune cells and adipocytes in epicardial adipose tissue (EAT). The expression of peroxisome proliferator receptor and genes in control of cell activation in macrophages and T cells in nonoccluded and occluded EAT increases in response to exercise.