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Abstract: SA-PO0872

Skeletal Muscle Transcriptomic Response to Resistance Exercise in Patients on Hemodialysis

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1500 Health Maintenance, Nutrition, and Metabolism

Authors

  • Ozcan, Bersan, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Demirci, Mert, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Norman, Jennifer E., University of California Davis, Davis, California, United States
  • Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States
  • Roshanravan, Baback, University of California Davis, Davis, California, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Gamboa, Jorge, University of Alabama at Birmingham Health System, Birmingham, Alabama, United States
Background

Patients on maintenance hemodialysis (MHD) experience sarcopenia, characterized by reduced muscle mass and strength. Exercise has been proposed as an intervention to prevent sarcopenia; however, most studies have demonstrated limited or no benefit. Resistance exercise is known to stimulate ribosomal biogenesis, but this mechanism has not been studied in MHD. Thus, we performed RNA sequencing (RNA-seq) analysis of skeletal muscle before and after 3 months of resistance exercise to identify differentially expressed genes (DEGs) in this population.

Methods

We conducted a 3-month intradialytic resistance training program in seven patients on MHD. Muscle biopsies were obtained before and after the intervention. Total RNA was extracted and used for RNA-seq using the Illumina NovaSeq 6000 system. DEGs were identified using a p-value < 0.01. Ribosomal biogenesis was assessed by quantifying total RNA normalized to tissue weight.

Results

Seven patients were included in the analysis based on the availability of paired muscle biopsies. The mean age was 38.5 ± 12 years; 66.6% were African American, the mean BMI was 27.2 ± 6 kg/m2, and all participants were male. After 3 months of resistance exercise, 32 DEGs were identified (p < 0.01). However, after false discovery rate adjustment, only one gene, ARID5B, remained statistically significant (p=0.01, Figure 1A). There was no significant change in total RNA content per mg of tissue following the intervention (Figure 1B).

Conclusion

We identified ARID5B as an upregulated gene. ARID5B is a regulator of adipogenesis and may explain the small increase in thigh cross-sectional area we previously observed, which was attributable to adipose tissue. The absence of increased ribosomal biogenesis is consistent with the lack of improvement in muscle cross-sectional area. Future studies should evaluate alternative strategies—such as high-intensity interval training, aerobic, or combined training, or longer-duration interventions—to better modulate gene expression and improve sarcopenia and frailty in this population.