Abstract: TH-PO899
Ketogenic Diet as a Protective Tool Against Progression to Diabetic Nephropathy in db/db Mice
Session Information
- Diabetic Kidney Disease: Basic - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Park, Woo Yeong, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Kim, Yaerim, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Paek, Jin hyuk, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Park, Sung Bae, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Han, Seungyeup, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Jin, Kyubok, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
Background
The prevalence of diabetic nephropathy (DN) is increasing rapidly worldwide. A recent research reported that a ketogenic diet (KD) may reverse pathological processes, but the mechanism is uncertain. The purpose of this study was to investigate the efficacy and mechanism of KD against progression of DN in db/db mice.
Methods
In vivo experiment, 5-week-old C57 BLKS/J lar-Leprdb/Leprdb mice (n=27) were divided into the three groups as follows: normal chow diet group (n=7), high fat diet group (n=9), and KD group (n=11). We measured the random glucose until ≥ 250 mg/dL until 7 weeks, and fasting glucose and body weight weekly after that. At 12 weeks, we analyzed urine albumin to creatinine ratio after collecting urine during 24 hours. At 16 weeks, we measured energy expenditure of mice using metabolic cage. We sacrificed mice at 18 weeks, and checked histological change, reactive oxygen species (ROS), and autophagy analysis. In vitro experiment, we evaluated ROS production in HK-2 cells, which are renal proximal tubule cells, with low and high glucose media with 3-beta hydroxybutyrate at 24 hours. We also analyzed autophagic flux activation in HK-2 cells for the evaluation of mechanism.
Results
Body weights were significantly lower in the KD group compared with other groups, but there was no significant difference in the fasting blood glucose level among three groups. Urinary albumin/creatinine ratio was significantly lower in the KD group compared with other groups. Serum BUN and creatinine were significantly lower in the KD group compared with other groups. Histology and quantitative analysis showed KD delayed the progression in view of less thickened glomerular basement membrane and smaller mesangial area. KD showed an antioxidant effect in DCF-DA+DAPI staining and ROS level, and increased autophagy via the change of p62, Nrf2, and LC3 expressions in vivo study. In vitro mechanistic study showed 3-beta hydroxybutyrate inhibited oxidative stress by decreased ROS level, and stimulated autophagy by increasing LC3 and Nrf2 in HK-2 cells. Finally, we validated the effect of KD by in vivo and in vitro studies.
Conclusion
This study showed that ketogenic diet might delay the progression of diabetic nephropathy by augmentation of autophagy and inhibition of oxidative stress and inflammation through in vivo and in vitro studies.