ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO620

Skeletal Muscle Mitochondrial Response to Wheel Running in a Rat Model of CKD

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1300 Health Maintenance, Nutrition, and Metabolism

Authors

  • Avin, Keith G., Indiana University-Indianapolis, Indianapolis, Indiana, United States
  • Hughes, Meghan C., York University , Toronto, Ontario, Canada
  • Srinivasan, Shruthi, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Chen, Neal X., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • O'Neill, Kalisha, Indiana University Medical Center, Indianapolis, Indiana, United States
  • Bacallao, Robert L., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Moe, Sharon M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Perry, Christopher G., York University , Toronto, Ontario, Canada
Background

We have previously found that treadmill running had detrimental effects upon mitochondrial pathways, while wheel running had multi-system beneficial effects in CKD rats. We hypothesized that wheel running would have beneficial effects on skeletal muscle mitochondria.

Methods

We used the Cy/+IU rat model of naturally occurring CKD (n = 12-14/group) to compare muscle bioenergetics in CKD rats versus NL littermates, and CKD versus CKD rats that performed 10 weeks of wheel running (from 25(~stage 2 CKD) to 35 weeks (~ESRD)). 1) Muscle protein lysates of the extensor digitorum longus (EDL, fast fiber type) and soleus (slow fiber type), were directly assessed for protein content of the mitochondrial respiratory subunit complexes by OXPHOS. 2) These muscles were permeabilized with direct assessment of mitochondrial respiration (Oxygraph-2k, Oroboros) in the presence of different substrates ((5Mm pyruvate, 2Mm malate; 25um-10mM ADP; 5mM glutamate; 20mM succinate).

Results

EDL: no difference in mitochondrial complex protein content or respiration in CKD vs NL. Wheel running reduced complexes I-IV subunit protein content (CKD-W vs CKD, p<0.05), but no difference respiration. Soleus: mitochondrial complex I was reduced in CKD vs NL, while complex III was reduced in the CKD-W vs CKD (both p<0.01). Respiration rates were increased in CKD (vs NL) for 300 and 500uM ADP (p<0.01), but not for state II (pyruvate, malate). In contrast, wheel running increased state II (i.e. pyruvate, malate) and 25uM ADP (compared to CKD; both p<0.01)) respiration.

Conclusion

Skeletal muscle from CKD rats did not demonstrate dramatic changes in mitochondrial content or respiration. Wheel running in CKD rats, compared to no wheel running, reduced isolated mitochondrial respiratory subunit content particularly in the EDL. Given there was no difference in respiration with lowered mitochondrial content there was a compensatory response. These data support that the systemic benefits of wheel running may not be due to direct changes in mitochondrial function in skeletal muscle, suggesting a more indirect effect.

Funding

  • NIDDK Support