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Abstract: FR-PO1103

Upregulation of the Ribosomal Pathway in Skeletal Muscle 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
  • Norman, Jennifer E., UC Davis Medical Center, Sacramento, California, United States
  • Ahmadi, Armin, University of California San Diego, La Jolla, California, United States
  • Begue, Gwenaelle, California State University Sacramento, Sacramento, California, United States
  • Roshanravan, Baback, UC Davis Medical Center, Sacramento, 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 with chronic kidney disease (CKD) undergoing hemodialysis (HD) exhibit a higher incidence of sarcopenia and frailty. Altered protein metabolism contributes to reduced muscle mass in this population. Given the essential role of ribosomes in protein synthesis, we hypothesized that the ribosomal pathway is dysregulated in the skeletal muscle of patients on HD.

Methods

In this cross-sectional study, we obtained vastus lateralis muscle biopsies from three groups matched for gender, body mass index (BMI), and diabetes history: healthy controls (n=13), patients with CKD stages 3–5 not on dialysis (CKD 3–5, n=13), and patients on HD (n=10). RNA sequencing data were analyzed using Gene Set Enrichment Analysis (GSEA) via WebGestalt 2019 to identify overrepresented cellular components. Ribosomal content was also assessed by measuring total RNA normalized to muscle weight.

Results

The groups were comparable in gender, BMI, and diabetes history. GSEA revealed significant upregulation of cytosolic ribosomal subunit components in the HD group compared to controls (41 differentially expressed genes; enrichment ratio = 9.9; FDR < 1×10-32). Figure 1A-B illustrates the upregulation of representative ribosomal genes in skeletal muscle of patients on HD. Ribosomal content was also elevated in the HD group (Figure 1C).

Conclusion

Our findings indicate an upregulation of ribosomal protein gene expression and increased ribosomal content in the skeletal muscle of patients on HD. This may reflect a compensatory response to the impaired protein synthesis previously reported in this population. Future studies should investigate whether ribosomal biogenesis is blunted in CKD in response to anabolic stimuli, such as resistance exercise, to identify potential therapeutic targets for preventing sarcopenia and frailty in CKD.

Funding

  • NIDDK Support

Digital Object Identifier (DOI)