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Abstract: TH-PO901

Comparison Study of Calorie-Matched High-Fat and High-Sugar Diets on Renal Injury with Lysosomal Dysfunction in Pre-Diabetic Mice

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Yoshimura, Aya, Fujita Health University, Toyoake, Aichi, Japan
  • Yamaguchi, Tamio, Suzuka University of Medical Science, Suzuka, Mie, Japan
  • Kugita, Masanori, Fujita Health University, Toyoake, Aichi, Japan
  • Kumamoto, Kanako, Fujita Health University, Toyoake, Aichi, Japan
  • Shiogama, Kazuya, Fujita Health University, Toyoake, Japan
  • Nagao, Shizuko, Fujita Health University, Toyoake, Aichi, Japan

Group or Team Name

  • Education and Research Center of Animal Models for Human Diseases,
Background

High fat and high sugar intakes are risk factors for diabetic nephropathy. However, no comparison study with calorie matched high fat and high sugar diets has been performed. In the present study, a high fat low carbohydrate (HFLC) diet and a normal fat high sugar (NFHS) diet, calorie/weight matched to the AIN93M standard rodent diet, were given to low dose streptozotocin (STZ) injected mice. Equal amounts of feed were given to determine whether HFLC or NFHS induce renal injury in the pre-diabetic stage.

Methods

CD1 male mice were randomly allocated to three pair-feeding groups from 7 to 20 weeks of age. The energy of all diets was 380 kilocalorie/100g. CONT: AIN93M diet with 10% (wt/wt) sucrose, 46.6% cornstarch, 15.5% alpha-cornstarch, 4% soybean oil; HFLC: diet with 31.1% alpha-cornstarch, 22% lard; NFHS: diet with 40.9% sucrose, 15.6% cornstarch, 15.5% alpha-cornstarch, 4% soybean oil. All other dietary ingredients were the same between diets. STZ (100mg/kg body wt) was injected at 17 and 18 weeks of age. Fasting blood glucose (FBG) was measured before and after STZ injection. After termination, kidneys were obtained for histology.

Results

Terminal body weight, total intake of food and energy, and serum creatinine level were not different between all groups. FBG was higher in HFLC but not in NFHS compared with CONT mice both before (at 17 weeks of age) and after STZ injection (at 20weeks of age). In kidney, the number of LAMP1 (lysosome-associated membrane protein 1)-positive vacuoles was significantly higher in HFLC compared with CONT and NFHS mice.

Conclusion

The present results suggest that the high fat diet, but not the high sugar diet, induces renal injury with impaired lysosome-mediated autophagic degradation, when total energy intake is identical in pre-diabetic mice.

Funding

  • Government Support - Non-U.S.