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Published on: April 17, 2021
Prebiotic prevents impaired kidney and renal Oat3 functions in obese rats
Keerati Wanchai1,2, Sakawdaurn Yasom3, Wannipa Tunapong1,4
1Department of PhysiologyFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Abstract:
Obesity is health issue worldwide, which can lead to kidney dysfunction. Prebiotics are non-digestible foods that have beneficial effects on health. This study aimed to investigate the effects of xylooligosaccharide (XOS) on renal function, renal organic anion transporter 3 (Oat3) and the mechanisms involved. High-fat diet was provided for 12 weeks in male Wistar rats. After that, the rats were divided into normal diet (ND); normal diet treated with XOS (NDX); high-fat diet (HF) and high-fat diet treated with XOS (HFX). XOS was given daily at a dose of 1000 mg for 12 weeks. At week 24, HF rats showed a significant increase in obesity and insulin resistance associated with podocyte injury, increased microalbuminuria, decreased creatinine clearance and impaired Oat3 function. These alterations were improved by XOS supplementation. Renal MDA level and the expression of AT1R, NOX4, p67phox, 4-HNE, phosphorylated PKCα and ERK1/2 were significantly decreased after XOS treatment. In addition, Nrf2-Keap1 pathway, SOD2 and GCLC expression as well as renal apoptosis were also significantly reduced by XOS. These data suggest that XOS could indirectly restore renal function and Oat3 function via the reduction of oxidative stress and apoptosis through the modulating of AT1R-PKCα-NOXs activation in obese insulin-resistant rats. These attenuations were instigated by the improvement of obesity, hyperlipidemia and insulin resistance.
Insights
Xylooligosaccharide (XOS) supplementation improved kidney function in obese rats by reducing oxidative stress and apoptosis. XOS also restored organic anion transporter 3 (Oat3) function, offering a potential therapeutic strategy for obesity-related kidney disease.
Area of Science:
- Nephrology
- Nutritional Science
- Biochemistry
Background:
- Obesity is a global health concern linked to kidney dysfunction.
- Prebiotics, like xylooligosaccharide (XOS), offer potential health benefits.
- Kidney dysfunction in obesity involves podocyte injury and impaired organic anion transporter 3 (Oat3) function.
Purpose of the Study:
- To investigate the effects of xylooligosaccharide (XOS) on renal function and Oat3 in obese rats.
- To elucidate the underlying mechanisms, including oxidative stress and apoptosis pathways.
Main Methods:
- Male Wistar rats were fed a high-fat diet for 12 weeks, followed by XOS supplementation (1000 mg/day) for another 12 weeks.
- Evaluated obesity, insulin resistance, renal function markers (microalbuminuria, creatinine clearance), and Oat3 function.
- Assessed oxidative stress markers (MDA, AT1R, NOX4, 4-HNE, PKCα, ERK1/2), Nrf2-Keap1 pathway, antioxidant enzymes (SOD2, GCLC), and renal apoptosis.
Main Results:
- High-fat diet induced obesity, insulin resistance, podocyte injury, and impaired Oat3 function.
- XOS treatment significantly improved renal function, attenuated oxidative stress, and reduced renal apoptosis.
- XOS modulated the AT1R-PKCα-NOXs pathway and improved the Nrf2-Keap1/SOD2/GCLC antioxidant defense system.
Conclusions:
- Xylooligosaccharide (XOS) ameliorates kidney dysfunction in obese, insulin-resistant rats.
- XOS restores renal and Oat3 function by reducing oxidative stress and apoptosis.
- These protective effects are mediated through the modulation of the AT1R-PKCα-NOXs pathway and enhancement of antioxidant defenses.
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