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Abstract: TH-PO195

L-Carnitine Ameliorates Diabetic Kidney Disease by Alleviating Mitochondrial Dysfunction in Spontaneously Diabetic Torii (SDT)-Fatty Rats

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Ito, Sakuya, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  • Taguchi, Kensei, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  • Kaida, Yusuke, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  • Kodama, Goh, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  • Moriyama, Tomofumi, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  • Yokota, Yunosuke, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
  • Fukami, Kei, Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan
Background

Abnormal fatty acid metabolism is associated with the progression of diabetic kidney disease (DKD). Carnitine plays a central role in fatty acid β-oxidation by transporting long-chain fatty acids from the cytoplasm to the mitochondria. Juvenile visceral steatosis (jvs) mice, described as an animal model for systemic carnitine deficiency, introduce a marked ectopic fat accumulation in the kidney. These findings suggest that abnormal carnitine dynamics in DKD cause ectopic fat accumulation due to abnormality of the fatty acid metabolism. However, the association between abnormalities of carnitine metabolism and the progression of DKD is unknown.

Methods

Spontaneously Diabetic Torii (SDT) fatty rat, an obese type 2 diabetic model was used. Unilateral nephrectomy was performed and 0.3% salt water was administered at 6 weeks of age, and created a renal dysfunction model in SDT fatty rat (DKD model). Age-matched male Sprague-Dawley (SD) rat was used as a control. Experiment 1: We compared 3 groups;SD rats (n=8), SDT fatty rats (n=8), DKD rats (n=8). Experiment 2: We compared 3 groups;SD rats with sham operation (n=8), DKD rats (n=7), DKD rats treated with L-carnitine administration (0.75% L-carnitine diet) for 10 weeks (n=6). All rats were sacrificed at 17 weeks old. Carnitine was measured by the tandem-mass spectrometry.

Results

Plasma and renal free carnitine levels and short/middle-long chain acylcarnitine ratio were significantly decreased in DKD rats compared with those in SD and SDT fatty rats. The renal expression levels of OCTN2, CPT1a, CPT2 and CrAT were significantly decreased in DKD rats. Similarly, PGC1α activity were decreased in DKD rats. L-carnitine administration significantly improved renal function, urinary albumin excretion, interstitial fibrosis and renal ectopic fat accumulation in DKD model rats. L-carnitine administration ameliorated the decrease of renal OCTN2, CPT1a, CPT2 and CrAT protein expression, and significantly improved PGC1α activity in DKD model rats. Furthermore, L-carnitine administration mitigated oxidation stress and mitochondrial dysfunction in DKD rats.

Conclusion

L-carnitine administration might be a promising therapeutic strategy for improving renal function by alleviating mitochondrial dysfunction in DKD rat model.