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bioRxiv · 10.1101/2025.02.02.635562

Aerobic exercise decreases the number and transcript expression of inflammatory M1 macrophages and CD8+ T cells in the epicardial adipose tissue of female pigs

Ahmad, I.·Gupta, S.·Thomas, M.·Cai, J. J.·Heaps, C. L.·Newell-Fugate, A. E.
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Abstract

BackgroundEpicardial adipose tissue (EAT) regulates coronary artery function via lipid metabolism and immune cell recruitment. Increased EAT is a risk factor for coronary artery disease (CAD), but aerobic exercise mitigates CAD. The effect of aerobic exercise on immune cells in EAT is unknown. We hypothesized that aerobic exercise creates an anti-inflammatory environment characterized by increased M2 macrophages and up-regulation of anti-inflammatory cytokine transcripts in EAT. MethodsFemale Yucatan pigs (n=7) were allocated to sedentary or exercised groups. To mimic CAD, a coronary artery was chronically occluded or remained non-occluded. EAT samples were processed for bulk and single nuclei transcriptomic sequencing. ResultsSub-clustering identified immune, endothelial, smooth muscle, adipocytes, adipocyte progenitor cells (APSCs), and neuronal cells, with adipocytes and APSCs being dominant. Non-occluded sedentary EAT had the largest percentage of M1 macrophages and CD8+ T cells. Irrespective of occlusion, sedentary EAT had the largest fraction of cells expressing genes in the tumor necrosis factor (TNF) superfamily. Irrespective of occlusion, exercise upregulated peroxisome proliferator-activated receptor (PPAR) gamma (G) expression and enriched PPAR signaling pathways in adipocytes, macrophages, and T cells. However, PPARG expression was lowest in CD8+ T cells from non-occluded exercised EAT. The greatest number of significant cell-cell communications between adipocytes and immune cells via growth factors and adhesion molecules occurred in occluded sedentary EAT. ConclusionAerobic exercise mitigates the proinflammatory nature of EAT in CAD via modulation of immune cell subpopulations, decreased TNF superfamily and increased PPARG gene expression, and decreased growth factor communication between adipocytes and immune cells.

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Ahmad, I., Gupta, S., Thomas, M., Cai, J. J., Heaps, C. L., Newell-Fugate, A. E.. 2025-02-03. Aerobic exercise decreases the number and transcript expression of inflammatory M1 macrophages and CD8+ T cells in the epicardial adipose tissue of female pigs. https://doi.org/10.1101/2025.02.02.635562

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