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Abstract: FR-PO1116

Exercise Alters the Single-Cell Transcriptome of Peripheral Blood Mononuclear Cells in Persons with CKD

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism

Authors

  • Norman, Jennifer E., University of California Davis, Davis, California, United States
  • Begue, Gwenaelle, University of California Davis, Davis, California, United States
  • Ahmadi, Armin, University of California Davis, Davis, California, United States
  • Gipe, Jesse, University of California Davis, Davis, California, United States
  • Gertz, Erik R., USDA-ARS Western Human Nutrition Research Center, Davis, California, United States
  • Bennett, Brian J., USDA-ARS Western Human Nutrition Research Center, Davis, California, United States
  • Kim, Tae Youn, University of California Davis, Davis, California, United States
  • Gamboa, Jorge, University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama, United States
  • Roshanravan, Baback, University of California Davis, Davis, California, United States
Background

Persons with chronic kidney disease (CKD) are at increased risk of sarcopenia and frailty, which may be mitigated by increased physical activity. In the ESTEEM-VIDA pilot randomized controlled trial (NCT02923063), we recently demonstrated that a 12-week home-based exercise intervention leads to improved physical endurance while reducing mitochondrial respiration rates in peripheral blood mononuclear cells (PBMCs). However, the mechanisms underlying these changes remain unknown.

Methods

We conducted a pilot single cell RNA sequencing analysis on PBMCs collected from three ESTEEM-VIDA trial participants before and after 12 weeks of exercise. Differential expression analyses were performed within lymphocyte and monocyte subsets, comparing post- to pre-exercise samples. Differentially expressed genes (DEGs) were defined as those with an adjusted p < 0.05 and an absolute value of log2 fold change ≥ 0.2.

Results

The participants consisted of two females and one male with ages ranging from 52 to 72 years and estimated glomerular filtration rates ranging from 20 to 42 mL/min/1.73m2. Global transcriptomic shifts were observed post-exercise (Figure 1), particularly in naïve CD4+ T cells and classical monocytes, which exhibited the most DEGs. DEGs shared across multiple cell types included downregulation of RN7SK, a small nuclear noncoding RNA involved in cell senescence, and upregulation of CCND3, encoding cyclin D3, which is involved in cell cycle regulation and linked to mitochondrial function.

Conclusion

A 12-week exercise intervention in persons with CKD induces transcriptomic changes in PBMCs, especially in naïve CD4+ T cells and classical monocytes. These changes may provide insight into the impact of exercise on inflammation and mitochondrial function in PBMCs in CKD patients.

Figure 1. Uniform manifold approximation and projection plots of sequenced cells color coded by cell type (A) and timing relative to the 12-week exercise intervention (B).

Funding

  • NIDDK Support

Digital Object Identifier (DOI)