Melatonin Administration Attenuates High-Fat-Diet-Induced Renal Damage in Wistar Rats

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.