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Abstract: TH-PO606

CD147/Basigin Is Involved in the Pathogenesis of Hepato-Renal Disease Under the Status of Satiation and Starvation

Session Information

Category: Health Maintenance, Nutrition, and Metabolism

  • 1301 Health Maintenance, Nutrition, and Metabolism: Basic

Authors

  • Ryuge, Akihiro, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Kosugi, Tomoki, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Sato, Yuka, University of Colorado, Aurora, United States
  • Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background

Gluconeogenesis from lactic acids and ketogenesis from fatty acids are critical for maintaining energy homeostasis and physiological activity during starvation in mammals. Besides ATP production necessary for substance transport by themselves, the kidneys are constantly complementing energy production of the liver which is a critical regulator in this setting. Therefore, excessive accumulation of glycogen and fat in metabolic syndrome causes chronic kidney disease and non-alcoholic fatty liver disease (NAFLD). CD147/Basigin (Bsg), a glycosylated transmembrane protein, is involved in glycolysis-lactate metabolism on carcinogenesis. We therefore investigated on physiologic functions of Bsg in energy metabolism under the status of satiation and starvation.

Methods

Two independent mice models were performed using wild-type (Bsg+/+) or Bsg-deficient (Bsg-/-) mice treated with high fat diet (HFD) or starvation (free drinking water), respectively.

Results

Levels of blood glucose (BS) and liver ATP in standard diet-fed Bsg-/- mice were lower than those of Bsg+/+ mice. Alternatively, activation of β-oxidation and autophagy were observed in the kidneys and liver of Bsg-/- mice. AMPK activation was also found in Bsg-/- liver. BS suppression in tolerance tests for pyruvate or alanine was exhibited, indicating that Bsg-/- mice showed a reduction of gluconeogenesis. In accordance with these findings, HFD-fed Bsg-/- mice ameliorated tubulointerstitial injury showing vacuolar formation, disease activity of NAFLD, and insulin resistance. Of note, starved Bsg-/- mice became NAFLD as well. This phenomenon might be caused by autophagic activation leading to the accumulation of triglyceride. Regardless of lower ATP values in Bsg-/- mice, surprisingly, life survival of Bsg-/- mice was similar with that of Bsg+/+ mice. The kidneys may compensate for energy shortage of Bsg-/- mice by activation of ketogenesis. Indeed, HMGCS2 that catalyzes the first reaction of ketogenesis was induced in Bsg-/- kidneys, but not liver.

Conclusion

CD147/Basigin is involved in the pathogenesis of hepato-renal disease through the regulation of autophagy, gluconeogenesis and ketogenesis under the status of satiation and starvation.