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Melatonin Administration Attenuates High-Fat-Diet-Induced Renal Damage in Wistar Rats
Olesia Kalmukova1, Anastasiia Zavora2,3, Alena Cherezova2
1Educational and Scientific Center "Institute of Biology and Medicine", Taras Shevchenko National University of Kyiv, 03022 Kyiv, Ukraine.
Abstract:
Obesity is a major contributor to kidney injury, in part through circadian rhythms disruption and oxidative stress. Melatonin, a circadian clock regulator, has been proposed as a protective agent against metabolic and renal complications. We investigated the effects of chronic melatonin supplementation on kidney injury and circadian regulation in a rat obesity model. We hypothesized that melatonin administration ameliorates kidney injury induced by a high-calorie diet. Male Wistar rats were fed a normal or hypercaloric diet for six weeks, followed by seven weeks of vehicle or melatonin treatment (30 mg/kg/day in drinking water); biometric parameters and renal injury were assessed. Obese rats exhibited increased visceral adiposity, elevated resistin, renal hypertrophy, fibrosis, tubular degeneration, and glomerular injury, accompanied by higher KIM-1 levels. Melatonin attenuated renal fibrosis, reduced KIM-1, TGFβ, and TNFR1 levels, improved proximal tubule and glomerular damage, and lowered adipose TNF-α levels in the obese groups. In lean controls, melatonin increased nuclear BMAL1 levels, while in obese rats this effect was blunted; of note, BMAL1 accumulated in distal tubular cytoplasm in both melatonin-treated groups. These findings suggest that melatonin mitigates obesity-induced renal pathology through anti-fibrotic inflammation-related mechanisms, while also revealing a novel link between circadian disruption and kidney injury. Our results support melatonin as a therapeutic agent for obesity-related renal disease.
Insights
Melatonin supplementation may protect against obesity-induced kidney injury by reducing fibrosis and inflammation. This study shows melatonin mitigates renal damage in obese rats, highlighting its therapeutic potential for metabolic and kidney diseases.
Area of Science:
- Nephrology
- Endocrinology
- Chronobiology
Background:
- Obesity is a significant risk factor for kidney injury, linked to circadian rhythm disruption and oxidative stress.
- Melatonin, a hormone regulating circadian rhythms, shows promise in protecting against metabolic and renal diseases.
Purpose of the Study:
- To investigate the protective effects of chronic melatonin supplementation on kidney injury in an established rat model of obesity.
- To explore melatonin's impact on circadian regulation and renal pathology in obese rats.
Main Methods:
- Male Wistar rats were fed a normal or high-calorie diet for six weeks.
- Subsequently, rats received either vehicle or melatonin (30 mg/kg/day) for seven weeks.
- Biometric parameters, visceral adiposity, resistin, renal injury markers (KIM-1, TGFβ, TNFR1), and circadian protein BMAL1 expression were assessed.
Main Results:
- Obese rats displayed increased adiposity, resistin, renal hypertrophy, fibrosis, tubular/glomerular damage, and elevated KIM-1.
- Melatonin treatment attenuated renal fibrosis, reduced KIM-1, TGFβ, TNFR1, and adipose TNF-α levels, and improved kidney histology in obese rats.
- Melatonin increased nuclear BMAL1 in lean rats but not obese rats, where BMAL1 accumulated in tubular cytoplasm, suggesting altered circadian regulation.
Conclusions:
- Melatonin mitigates obesity-induced renal pathology via anti-fibrotic and anti-inflammatory mechanisms.
- The study reveals a novel connection between circadian disruption and kidney injury in obesity.
- Melatonin demonstrates therapeutic potential for managing obesity-related kidney disease.
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