Abstract: TH-PO399

Abnormal Lipid Metabolism in Skeletal Muscle Mediates CKD-Induced Sarcopenia

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Niida, Yuki, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Miyazaki, Makoto, University of Colorado Denver,, Aurora, Colorado, United States
  • Yamamoto, Hironori, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Taketani, Yutaka, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Masuda, Masashi, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Yoshizawa, Aika, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Adachi, Yuichiro, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Yimamu, Yilimulati, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Kabutoya, Serina, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Yoshida, Risa, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Okumura, Hisami, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
  • Kawai, Yoshichika, Institute of Biomedical Sciences, Tokushima University Graduate School , Tokushima, Japan
Background

Sarcopenia is defined by decreased skeletal muscle mass and strength.Chronic kidney disease (CKD)-induced sarcopenia is associated with degraded quality of life and poor prognosis of the patient. However, there is currently no effective therapy available because the mechanisms of its pathogenesis are largely unknown. Recent evidence indicates that CKD increases circulating levels of the major saturated fatty acid stearic acid through repression of stearoyl-CoA desaturase (SCD), which induces lipotoxicities such as ER stress in tissues, including cardiovascular tissues. Several reports have also indicated that ER stress plays a causative role in sarcopenia and cahexia. In this study, we examined the role of ER stress via abnormal lipid metabolism in the skeletal muscles of CKD rats with muscle atrophy.

Methods

Eight-week-old male Wistar rats were treated with either adenine diet (0.4%) (CKD rats) or vehicle (normal rats) for 6 weeks. Gastrocnemius muscles(GM), soleus muscles, tibialis anterior muscles, and extensor digitorum longus muscles were weighed and atrophy was evaluated by hematoxylin and eosin (H&E) staining. Gene expression of gastrocnemius muscles was evaluated by real-time qPCR. Fatty acid composition of gastrocnemius muscles was determined by the gas-liquid chromatography method.

Results

GM tissue weight was significantly decreased in CKD rats compared with normal rats. We confirmed infiltration of inflammatory cells and increased connective tissue in the GM of CKD rats by H&E staining. mRNA expression of muscle atrophy-related genes and ER stress responsive genes were increased in the GM of CKD rats compared with normal rats. Inversely, CKD rats presented a decrease in SCD1 mRNA expression of the GM compared with normal rats. In addition, the unsaturated fatty acid ratio (UFA/SFA) was significantly lower in the GM of CKD rats compared with normal rats. In mouse myoblasts, administration of SCD inhibitor increased mRNA expression of muscle atrophy-relating genes and ER stress response genes.

Conclusion

We suggest that the unbalanced SFA/UFA ratio in skeletal muscles due to a decrease in SCD activity induced by CKD causes lipotoxicity and sarcopenia via activation of various muscle atrophy systems.