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3-Hydroxybutyrate Ameliorates the Progression of Diabetic Nephropathy

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Author(s)
Jeeyoun JungWoo Yeong ParkYun Jin KimMikyung KimMisun ChoeKyubok JinJi Hae SeoEunyoung Ha
Keimyung Author(s)
Park, Woo YoungChoe, Mi SunJin, Kyu BokSeo, Ji HyeHa, Eun Young
Department
Dept. of Internal Medicine (내과학)
Dept. of Pathology (병리학)
Dept. of Biochemistry (생화학)
Journal Title
Antioxidants (Basel)
Issued Date
2022
Volume
11
Issue
2
Keyword
diabetic nephropathy3-hydroxybutyrateoxidative stressautophagy
Abstract
Studies report beneficial effects of 3-hydroxybutyrate (3-OHB) on the treatment of type 2 diabetes and obesity, but the effects of 3-OHB on diabetic nephropathy have not been elucidated. This study was designed to investigate the efficacy and mechanism of 3-OHB against progression of diabetic nephropathy (DN). Mice (db/db) were fed normal chow, high-fat, or ketogenic diets (KD) containing precursors of 3-OHB. Hyperglycemia was determined based on random glucose level (≥250 mg/dL). Fasting blood glucose and body weights were measured once a week. Twenty four-hour urine albumin to creatinine ratio was determined 5 weeks after the differential diet. Energy expenditure was measured 9 weeks after the differential diet. Body weights were significantly lower in the KD group than those in other groups, but no significant differences in fasting blood glucose levels among three groups were observed. Urine albumin to creatinine ratio and serum blood urea nitrogen (BUN) to creatinine ratio in the KD group were significantly lower than in other groups. Histologic and quantitative analysis of mesangial area suggested that KD delayed the progression of DN phenotype in db/db mice. Metabolic cage analysis also revealed that KD increased energy expenditure in db/db mice. In vitro studies with proximal tubular cells revealed that 3-OHB stimulated autophagic flux. 3-OHB increased LC3 I to LC3 II ratio, phosphorylation of AMPK, beclin, p62 degradation, and NRF2 expression. Moreover, we found that 3-OHB attenuated high glucose-induced reactive oxygen species (ROS) levels in proximal tubular cells. In vivo study also confirmed increased LC3 and decreased ROS levels in the kidney of KD mice. In summary, this study shows in both in vivo and in vitro models that 3-OHB delays the progression of DN by augmenting autophagy and inhibiting oxidative stress.
Keimyung Author(s)(Kor)
박우영
최미선
진규복
서지혜
하은영
Publisher
School of Medicine (의과대학)
Citation
Jeeyoun Jung et al. (2022). 3-Hydroxybutyrate Ameliorates the Progression of Diabetic Nephropathy. Antioxidants (Basel), 11(2), 381. doi: 10.3390/antiox11020381
Type
Article
ISSN
2076-3921
Source
https://www.mdpi.com/2076-3921/11/2/381
DOI
10.3390/antiox11020381
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/44169
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Biochemistry (생화학)
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
1. School of Medicine (의과대학) > Dept. of Pathology (병리학)
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