Abstract: TH-PO630
Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice
Session Information
- Health Maintenance, Nutrition, Metabolism - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Health Maintenance, Nutrition, and Metabolism
- 1300 Health Maintenance, Nutrition, and Metabolism
Authors
- Fukushima, Kazuhiko, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Scineces, Okayama, Japan
- Kitamura, Shinji, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Scineces, Okayama, Japan
- Tsuji, Kenji, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Scineces, Okayama, Japan
- Sang, Yizhen, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Scineces, Okayama, Japan
- Wada, Jun, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Scineces, Okayama, Japan
Background
Obesity is supposed to cause to renal injury, and sodium glucose co-transporter 2 inhibitors (SGLT2-I) are reported to have possibilities to protect renal disorders. However, the SGLT2-I direct protective mechanism has been unclear. In this study, we investigated SGLT2-I effects focused on autophagic flux impairment in proximal tubular cells in obesity mice.
Methods
5-week-old C57BL/6J mice were divided to normal diet (ND) fed group or 40 kcal % fat diet (HFD) fed group. After 9 weeks, we separated the mice, administrated 10.0 mg/kg/day SGLT2-I (empagliflozin provided from Boehringer-Ingelheim) group or solvent, hydroxypropyl methylcellulose (HPMC) group to each feeding group mice for 1 week. After total 10 weeks, urine was harvested for 24 hrs with ND. The mice were sacrificed, and serum plasma and kidneys were harvested. We investigated pathological analysis and protein expression focused on autophagy.
Results
The weight of HFD mice gained significantly than that of ND mice. HFD-SGLT2-I mice showed significant decrease of urinary N-acetyl-β-D-glycosaminidase (NAG) compared with HFD-HPMC group (p < 0.05). In oil red O staining, lipid accumulations were observed on proximal tubular cells in HFD-HPMC treated mice, however lipid accumulations were observed significantly decrease in HFD-SGLT2-I fed mice. HFD-HPMC mice showed significantly increase of p62 positive proximal tubules compared to ND-HPMC group. Interestingly, HFD- SGLT2-I showed significant decrease compared to HFD-HPMC group (p < 0.05). In electron microscopy, multilamellar bodies (MLBs), which shows the autophagosome or autolysosome storing lipids, appeared in proximal tubular cells of HFD-HPMC mice, however MLBs decreased in HFD-SGLT2-I group. In addition, abnormal formation of mitochondria was observed in proximal tubular cells of HFD-mice, and several mitophagosomes were observed in those treated with SGLT2-I.
Conclusion
SGLT2-I might have renal protective effects against obesity via improving autophagic flux impairment in proximal tubular cells by promoting autophagosomal degradation of lipids and damaged mitochondrias.